The cGAS–STING pathway plays an important role in ischemia-reperfusion injury in the heart,liver,brain,and kidney,but its role and mechanisms in cerebral ischemia-reperfusion injury have not been systematically revie...The cGAS–STING pathway plays an important role in ischemia-reperfusion injury in the heart,liver,brain,and kidney,but its role and mechanisms in cerebral ischemia-reperfusion injury have not been systematically reviewed.Here,we outline the components of the cGAS–STING pathway and then analyze its role in autophagy,ferroptosis,cellular pyroptosis,disequilibrium of calcium homeostasis,inflammatory responses,disruption of the blood–brain barrier,microglia transformation,and complement system activation following cerebral ischemia-reperfusion injury.We further analyze the value of cGAS–STING pathway inhibitors in the treatment of cerebral ischemia-reperfusion injury and conclude that the pathway can regulate cerebral ischemia-reperfusion injury through multiple mechanisms.Inhibition of the cGAS–STING pathway may be helpful in the treatment of cerebral ischemia-reperfusion injury.展开更多
Early or ultra-early pharmacological thrombolysis together with mechanical thrombectomy are key treatments for ischemic stroke,and both are aimed at vascular recanalization and improved collateral circulation.While th...Early or ultra-early pharmacological thrombolysis together with mechanical thrombectomy are key treatments for ischemic stroke,and both are aimed at vascular recanalization and improved collateral circulation.While these methods enhance tissue perfusion in the ischemic penumbra,they also trigger complex neurotoxic reactions,including apoptosis,acidosis,ion imbalance,oxidative stress,and pyroptosis,exacerbating cerebral ischemia-reperfusion injury(CIRI).Pyroptosis,a recently discovered form of programmed cell death driven by inflammation,plays a significant role in neuronal death during CIRI.This study reviews the regulatory mechanisms of pyroptosis in CIRI.展开更多
Cerebral ischemia-reperfusion is a process in which the blood supply to the brain is temporarily interrupted and subsequently restored.However,it is highly likely to lead to further aggravation of pathological damage ...Cerebral ischemia-reperfusion is a process in which the blood supply to the brain is temporarily interrupted and subsequently restored.However,it is highly likely to lead to further aggravation of pathological damage to ischemic tissues or the nervous system.,and has accordingly been a focus of extensive clinical research.As a traditional Chinese medicinal formulation,Sanhua Decoction has gradually gained importance in the treatment of cerebrovascular diseases.Its main constituents include Citrus aurantium,Magnolia officinalis,rhubarb,and Qiangwu,which are primarily used to regulate qi.In the treatment of neurological diseases,the therapeutic effects of the Sanhua Decoction are mediated via different pathways,including antioxidant,anti-inflammatory,and neurotransmitter regu-latory pathways,as well as through the protection of nerve cells and a reduction in cerebral edema.Among the studies conducted to date,many have found that the application of Sanhua Decoction in the treatment of neurological diseases has clear therapeutic effects.In addition,as a natural treatment,the Sanhua Decoction has received widespread attention,given that it is safer and more effective than traditional Western medicines.Consequently,research on the mechanisms of action and efficacy of the Sanhua Decoctions in the treatment of cerebral ischemia-reperfusion injury is of considerable significance.In this paper,we describe the pathogenesis of cerebral ischemia-reperfusion injury and review the current status of its treatment to examine the therapeutic mechanisms of action of the Sanhua Decoction.We hope that the findings of the research presented herein will contribute to a better understanding of the efficacy of this formulation in the treatment of cerebral ischemia-reperfusion,and provide a scientific basis for its application in clinical practice.展开更多
Despite improvement in cardiopulmonary resuscitation(CPR)performance,cardiac arrest(CA)is still associated with poor prognosis.The high mortality rate is due to multi-organ dysfunction caused by cerebral ischemia and ...Despite improvement in cardiopulmonary resuscitation(CPR)performance,cardiac arrest(CA)is still associated with poor prognosis.The high mortality rate is due to multi-organ dysfunction caused by cerebral ischemia and reperfusion injury(I/R).The guidelines for CPR suggest the use of therapeutic hypothermia(TH)as an effective treatment to decrease mortality and the only approach confirmed to reduce I/R injury.During TH,sedative agents(propofol)and analgesia agents(fentanyl)are commonly used to prevent shiver and pain.However,propofol has been associated with a number of serious adverse effects such as metabolic acidosis,cardiac asystole,myocardial failure,and death.In addition,mild TH alters the pharmacokinetics of agents(propofol and fentanyl)and reduces their systemic clearance.For CA patients undergoing TH,propofol can be overdosed,leading to delayed awakening,prolonged mechanical ventilation,and other subsequent complications.Ciprofol(HSK3486)is a novel anesthetic agent that is convenient and easy to administer intravenously outside the operating room.Ciprofol is rapidly metabolized and accumulates at low concentrations after continuous infusion in a stable circulatory system compared to propofol.Therefore,we hypothesized that treatment with HSK3486 and mild TH after CA could protect the brain and other organs.展开更多
Cerebral ischemia-reperfusion injury(CI/RI)remains the main cause of disability and death in stroke patients due to lack of effective therapeutic strategies.One of the main issues related to CI/RI treatment is the pre...Cerebral ischemia-reperfusion injury(CI/RI)remains the main cause of disability and death in stroke patients due to lack of effective therapeutic strategies.One of the main issues related to CI/RI treatment is the presence of the blood-brain barrier(BBB),which affects the intracerebral delivery of drugs.Ginkgolide B(GB),a major bioactive component in commercially available products of Ginkgo biloba,has been shown significance in CI/RI treatment by regulating inflammatory pathways,oxidative damage,and metabolic disturbance,and seems to be a candidate for stroke recovery.However,limited by its poor hydrophilicity and lipophilicity,the development of GB preparations with good solubility,stability,and the ability to cross the BBB remains a challenge.Herein,we propose a combinatorial strategy by conjugating GB with highly lipophilic docosahexaenoic acid(DHA)to obtain a covalent complex GB-DHA,which can not only enhance the pharmacological effect of GB,but can also be encapsulated in liposomes stably.The amount of finally constructed Lipo@GB-DHA targeting to ischemic hemisphere was validated 2.2 times that of free solution in middle cerebral artery occlusion(MCAO)rats.Compared to the marketed ginkgolide injection,Lipo@GB-DHA significantly reduced infarct volume with better neurobehavioral recovery in MCAO rats after being intravenously administered both at 2 h and 6 h post-reperfusion.Low levels of reactive oxygen species(ROS)and high neuron survival in vitro was maintained via Lipo@GB-DHA treatment,while microglia in the ischemic brain were polarized from the pro-inflammatory M1 phenotype to the tissue-repairing M2 phenotype,which modulate neuroinflammatory and angiogenesis.In addition,Lipo@GB-DHA inhibited neuronal apoptosis via regulating the apoptotic pathway and maintained homeostasis by activating the autophagy pathway.Thus,transforming GB into a lipophilic complex and loading it into liposomes provides a promising nanomedicine strategy with excellent CI/RI therapeutic efficacy and industrialization prospects.展开更多
Stroke remains a worldwide health problem. Salvianolate exerts a protective effect in various mi- crocirculatory disturbance-related diseases, but studies of the mechanisms underlying its protective action have mainly...Stroke remains a worldwide health problem. Salvianolate exerts a protective effect in various mi- crocirculatory disturbance-related diseases, but studies of the mechanisms underlying its protective action have mainly focused on the myocardium, whereas little research has been carried out in brain tissue following ischemia-reperfusion. We assessed the neuroprotective effects of salvianolate in a rat model of cerebral ischemia-reperfusion injury induced using the suture method. At onset and 24 and 48 hours after reperfusion, rats were intraperitoneally injected with salvianolate （18 mg/kg） or saline. Neurological deficit scores at 72 hours showed that the neurological functions of rats that had received salvianolate were significantly better than those of the rats that had received saline. 2,3,5-Triphenyltetrazolium chloride was used to stain cerebral tissue to determine the extent of the infarct area. A significantly smaller infarct area and a significantly lower number of apoptotic cells were observed after treatment with salvianolate compared with the saline treatment. Expression of heat shock protein 22 and phosphorylated protein kinase B in ischemic brain tissue was significantly greater in rats treated with salvianolate compared with rats treated with saline. Our findings suggest that salvianolate provides neuroprotective effects against cerebral ischemia-reperfusion injury by upregulating heat shock protein 22 and phosphorylated protein kinase B expression.展开更多
BACKGROUND： The pharmacological effects of aspirin on apoptosis are complex. The underlying mechanisms have not been properly defined. OBJECTIVE： To observe the effect of different doses of aspirin on brain cell apo...BACKGROUND： The pharmacological effects of aspirin on apoptosis are complex. The underlying mechanisms have not been properly defined. OBJECTIVE： To observe the effect of different doses of aspirin on brain cell apoptosis following focal cerebral iscbemia-reperfusion injury （CIRI） in rats. DESING, TIME AND SETTING： A randomized, controlled, animal experiment, performed at the School of Medicine and Pharmaceutics, Jiangnan University between June and October 2006. MATERIALS： Twenty-six male, adult, Sprague Dawley rats （grade Ⅱ）, weighing 240-290 g, were obtained from Shanghai Experimental Animal Center, Chinese Academy of Sciences. Aspirin was provided by Sigma （USA）. METHODS： The rats were randomly divided into four groups： sham-operation （SO）, CIRI ＋ vehicle, CIRI ＋ aspirin （6 mg/kg）, and CIRI ＋ aspirin （60 mg/kg）. Rats in the lesion groups were intragastrically administrated saline, aspirin （6 mg/kg）, or aspirin （60 mg/kg）, respectively. MAIN OUTCOME MEASURES： The number of pyramidal neurons with normal appearance in the cerebral cortex at 24 mm from the midline; apoptotic cell death as measured by TUNEL; Bcl-2 and Bax protein localization was determined by immunohistochemistry; malondialdehyde （MDA） and super oxidation （SOD） content were determined by biochemistry method; adenosine triphosphate （ATP） content measured by capillary electrophoresis. RESULTS： Following CIRI, the following parameters were altered compared with sham-operated animals： the number of neurons with normal appearance was significantly reduced in the cerebral cortex; the number of apoptotic cells increased; Bax protein expression was enhanced; and the ratio between Bcl-2 and Bax decreased. In addition, MDA content increased significantly, whereas ATP content decreased （P 〈 0.01）. Aspirin ameliorated the loss of healthy pyramidal neurons. Both 6 and 60 mg/kg aspirin increased the ratio between Bcl-2 and Bax, with no significant difference between the treatment groups. In addition, 60 mg/kg aspirin decreased MDA content and increased ATP levels. However, 6 mg/kg aspirin did not have the same effect. CONCLUSION： Aspirin reduced the number of apoptotic cells following CIRI. These results suggest that the neuroprotective mechanism of aspirin could be related to elevated Bcl-2 protein levels or decreased Bax protein expression. The increase in the ratio of Bcl-2 to Bax appears to be a common anti-apoptotic mechanism of aspirin.展开更多
We investigated nerve growth factor precursor （proNGF） and mature NGF expression in ischemic and non-ischemic cortices after cerebral ischemia-reperfusion injury. In both ischemic and non-ischemic cortices, proNGF w...We investigated nerve growth factor precursor （proNGF） and mature NGF expression in ischemic and non-ischemic cortices after cerebral ischemia-reperfusion injury. In both ischemic and non-ischemic cortices, proNGF was found to be present in the extracellular space and cytoplasm. In addition, mature NGF was expressed in extracellular space, but with a very low signal. In ischemic cortex only, proNGF was significantly decreased, reaching a minimal level at 1 day. Mature NGF was increased at 4 hours, then reached a minimal level at 3 days. The p75 neurotrophin receptor （p75NTR） was significantly decreased after ischemia, and increased at 3 days after ischemia. These results confirmed that proNGF was the predominant form of NGF during the pathological process of cerebral ischemia-repeffusion injury. In addition, our findings suggest that ischemic injury may influence the conversion of proNGF to mature NGF, and that proNGF/p75NTR may be involved in reperfusion injury.展开更多
Penehyclidine hydrochloride can promote microcirculation and reduce vascular permeability. However, the role of penehyclidine hydrochlodde in cerebral ischemia-reperfusion injury remains unclear. In this study, in viv...Penehyclidine hydrochloride can promote microcirculation and reduce vascular permeability. However, the role of penehyclidine hydrochlodde in cerebral ischemia-reperfusion injury remains unclear. In this study, in vivo middle cerebral artery occlusion models were established in experimental rats, and penehyclidine hydrochloride pretreatment was given via intravenous injection prior to model establishment. Tetrazolium chloride, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling and immunohistochemical staining showed that, penehyclidine hydrochloride pretreatment markedly attenuated neuronal histopathological changes in the cortex, hippocampus and striatum, reduced infarction size, increased the expression level of BcI-2, decreased the expression level of caspase-3, and inhibited neuronal apoptosis in rats with cerebral ischemia-reperfusion injury. Xanthine oxidase and thiobarbituric acid chromogenic results showed that penehyclidine hydrochloride upregulated the activity of superoxide dismutase and downregulated the concentration of malondialdehyde in the ischemic cerebral cortex and hippocampus, as well as reduced the concentration of extracellular excitatory amino acids in rats with cerebral ischemia-reperfusion injury. In addition, penehyclidine hydrochloride inhibited the expression level of the NR1 subunit in hippocampal nerve cells in vitro following oxygen-glucose deprivation, as detected by PCR. Experimental findings indicate that penehyclidine hydrochloride attenuates neuronal apoptosis and oxidative stress injury after focal cerebral ischemia-reperfusion, thus exerting a neuroprotective effect.展开更多
BACKGROUND： Somatosensory evoked potential （SEP） has become a method with higher sensitivity and specificity than electroencephalogram in detecting the brain function and the region, range and degree of ischemia. H...BACKGROUND： Somatosensory evoked potential （SEP） has become a method with higher sensitivity and specificity than electroencephalogram in detecting the brain function and the region, range and degree of ischemia. However, the effects of ligustrazine on SEP is still not clear. OBJECTIVE ： To study the protective effects of ligustrazini injection on cerebral ischemia-reperfusion injury.DESIGN： Auto-control study, random grouping.SETTING： Qilu Hospital of Shandong University.MATERIALS： The experiment was completed in the Cerebral Functional Room of Qilu Hospital Affiliated to Shandong University from March 2002 to June 2004. A totally of 24 healthy Harbin rabbits were randomly divided into blank control group （n=8）, model control group （n=8） and ligustrazine treatment group （n=8）. Hydrochloric ligustrazine injection, 40 mg/2 mL each ampoule, was provided by the Third Pharmaceutical Factory of Beijing （certification： 93035236273）. The main component was hydrochloric ligustrazine and the chemical name was 2, 3, 5, 6-tetramethyl pyrazine hydrochloride. METHODS：① Modeling method： The bilateral common carotid artery ligation was adopted to make the model. ② Index of cerebral functional lesion evaluated with SEP during ischemia-reperfusion： DISA 2000C neuromyoeletrometer provided by Dantec Electronics Ltd, Denmark was used to detect SEP. ③ Interventional process： Blank control group： The latencies and amplitudes of SEP were measured before injection with 1.5 mg/kg ligustrazine and at the points of 15 minutes, 20 minutes, 30 minutes, 60 minutes, 90 minutes and 120 minutes after injection. Ligustrazine treatment group： Rabbits were injected with 1.5 mg/kg ligustrazine, and those of model control group were injected the same volume of saline. Thirty minutes later, the bilateral common carotid artery of the rabbits all had been ligated for 30 minutes, and then reperfused for 120 minutes. The latencies and amplitudes of SEP were measured before injection, before ligation, at the points of 1 minute, 5 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes and 30 minutes after ligation, and at the points of 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes, 60 minutes, 90 minutes and 120 minutes after reperfusion.④ Evaluating criteria： Normal values of P-wave latencies and amplitudes were （19.34±3.18） ms and （4.55±1.43）μV. Average value before injection in blank control group and average values before injection, after injection and before ligation in ischemiareperfusion group were regarded as control criteria to evaluate changes of P-wave latencies and amplitudes after experiment. MAIN OUTCOME MEASURES： P-wave latencies and amplitudes of SEP in the three groups.RESULTS ： A total of 24 rabbits were involved in the final analysis without any loss.① Blank control group： The P-wave latencies delayed markedly at each time point after injection. Compared with that before injection, there was a significant difference （P 〈 0.05-0.01）. The P-wave amplitudes did not fluctuate noticeably all the time after injection, but significantly decreased when compared with those before injection （P 〈 0.05-0.01）. ② Ischemia-reperfusion group： The P-wave latencies delayed and amplitudes decreased in the rabbits with cerebral ischemia-reperfusion at all points of time during cerebral ischemia-reperfusion, and there was significant difference when compared with the levels before ischemia （P 〈 0.05）. When ligustrazine was injected, the latencies and amplitudes changed less, and as compared with the levels before ischemia, the difference was not significant （P〉 0.05）.CONCLUSION：① Ligustrazine can inhibit P-wave latencies and amplitudes of SEP of normal rabbits.②Ligustrazine can improve P-wave latencies and amplitudes of SEP of rabbits with cerebral ischemia-reperfusion injury.展开更多
BACKGROUND： HOW to control the effect of oxygen-derived free radicals on development of cerebral injury and cerebral edema is a key factor for treating cerebral ischemia-reperfusion injury. OBJECTIVE： To observe and...BACKGROUND： HOW to control the effect of oxygen-derived free radicals on development of cerebral injury and cerebral edema is a key factor for treating cerebral ischemia-reperfusion injury. OBJECTIVE： To observe and compare the protective effects, synergistic action and mechanisms of ultrashortwave （USW） and radix salviae miltiorrhizae （RSM） on the focal cerebral ischemia-reperfusion injuries in rats. DESIGN： Randomized controlled animal study SEI-FING： Department of Rehabilitation Medicine, First Hospital affiliated to China Medical University MATERIALS： A total of 160 healthy Wistar rats of both genders and aged 18-20 weeks weighing 250-300 g of clean grade were selected in this study. 5 mL/ampoule RSM injection fluid was produced by the First Pharmaceutical Corporation of Shanghai （batch number： 011019, 0.01 mug）. The USW therapeutic device was produced by Shanghai Electronic Device Factory with the frequency of 40.68 MHz and the maximal export power of 40 W. The first channel of power after modulation was 11 W. METHODS： The experiment was carried out in the Rehabilitation Medicine Department of the First Hospital affiliated to China Medical University from May 2002 to January 2003. Focal ischemia-reperfusion model was established in rats by reversible right middle cerebral artery occlusion with filament. Right cerebral ischemia was for 2 hours and then with 24 hours reperfusion. The scores of neurological deficits were evaluated by 0 to 4 scales. After surgery, 64 successful rats models were divided into four groups according to digital table： control group, USW group, RSM group and RSM ＋ USW group with 16 cases in each group. Rats in control group were intraperitoneally injected with the same volume of saline （0.1 mL/g）; rats in USW group were given small dosage of USW on head for 10 minutes at 6 hours after reperfusion; rats in RSM group were intraperitoneally injected with 0.01 mL/g RSM solution at 30 minutes before reperfusion; rats in RSM ＋ USW group were intraperitoneally injected with 0.01 mL/g RSM parenteral solution at 30 minutes before reperfusion and given small dosage of USW on head for 10 minutes once at 6 hours after reperfusion; sixteen rats in sham operation group did not receive any treatment. All 80 rats were taken brains at 24 hours after reperfusion to measure wet and dry weights to calculate water content： Cerebral water content （%） = （1-dry/wet weight） × 100%. Superoxide dismutase （SOD） activity was measured by hydroxylamine method and malondialdehyde （MDA） content was measured by TBA photometric method. MAIN OUTCOME MEASURES ： Cerebral water content, SOD activity and MDA content RESULTS： All 160 rats except 80 failing in modeling were involved in the final analysis. （① The cerebral water content of left hemisphere made no significant difference （P 〉 0.05）. The cerebral water content of right hemisphere in the control group and the three treatment groups was obviously higher than that of the sham operation group [（81.26±0.77）%, （79.74±0.68）%, （79.76±0.81）%, （79.61±0.79）%, （77.43±0.61）%, P 〈 0.05]. The cerebral water content of right hemisphere in the three treatment groups was obviously lower than that of the control group （P〈 0.05）. There was no significant difference among the three treatment groups （P 〉 0.05）. ② Compared with the control group, SOD activity （right） of the control group decreased obviously （P 〈 0.05）, while MDA content increased obviously （P 〈 0.05）. SOD activity in the three therapeutic groups increased obviously, while MDA content decreased obviously （P 〈 0.05）; there was no significant difference among the three treatment groups （P 〉 0.05）. CONCLUSION： ① USW and RSM therapy have neuroprotective effects against focal cerebral ischemia-reperfusion injuries by means of decreasing cerebral water content and MDA and increasing the activity of SOD. ② Synergistic action was not observed between these two therapeutic methods.展开更多
Objective To clarify the effects of repetitive transcranial magnetic stimulation (rTMS) on rat motor cortical excitabi- lity and neurofunction after cerebral ischemia-reperfusion injury. Methods After determined awake...Objective To clarify the effects of repetitive transcranial magnetic stimulation (rTMS) on rat motor cortical excitabi- lity and neurofunction after cerebral ischemia-reperfusion injury. Methods After determined awake resting motor threshold (MT) and motor evoked potentials (MEPs) of right hindlimbs, 20 Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) reperfusion injury, then rTMS were applied to rTMS group (n = 10) at different time, while control group (n = 10) received no stimulation. A week later, MT and MEPs were evaluated again, as well as neurological deficits and infarct volume. The effects of rTMS and MCAO reperfusion injury on these parameters were analyzed. Results After MCAO reperfusion, both MT level and neurological deficit scores increased, distinct focal infarction formed, and latency of MEP elongated. Compared with the control group, the increased extent of MT and neurological scores of rats receiving rTMS were significantly lower (P < 0.05), as well as the infarct volumes reduced significantly(P < 0.05). But MEP was not affected by rTMS obviously. There was a positive linear correlation between postinjury MT and infarct volume (r = 0.64, P < 0.05). Conclusion rTMS may facilitate neurofunction recovery after cerebral ischemia-reperfusion. Postinjury MT could provide prognostic information after MCAO reperfusion injury.展开更多
Acacetin(5,7-dihydroxy-4′-methoxyflavone), a potential neuroprotective agent, has an inhibitory effect on lipopolysaccharide-induced neuroinflammatory reactions. However, whether acacetin has an effect on inflammator...Acacetin(5,7-dihydroxy-4′-methoxyflavone), a potential neuroprotective agent, has an inhibitory effect on lipopolysaccharide-induced neuroinflammatory reactions. However, whether acacetin has an effect on inflammatory corpuscle 3(NLRP3) after cerebral ischemia-reperfusion injury has not been fully determined. This study used an improved suture method to establish a cerebral ischemia-reperfusion injury model in C57BL/6 mice. After ischemia with middle cerebral artery occlusion for 1 hour, reperfusion with intraperitoneal injection of 25 mg/kg of acacetin(acacetin group) or an equal volume of saline(0.1 mL/10 g, middle cerebral artery occlusion group) was used to investigate the effect of acacetin on cerebral ischemia-reperfusion injury. Infarct volume and neurological function scores were determined by 2,3,5-triphenyltetrazolium chloride staining and the Zea-Longa scoring method. Compared with the middle cerebral artery occlusion group, neurological function scores and cerebral infarction volumes were significantly reduced in the acacetin group. To understand the effect of acacetin on microglia-mediated inflammatory response after cerebral ischemia-reperfusion injury, immunohistochemistry for the microglia marker calcium adapter protein ionized calcium-binding adaptor molecule 1(Iba1) was examined in the hippocampus of ischemic brain tissue. In addition, tumor necrosis factor-α, interleukin-1β, and interleukin-6 expression in ischemic brain tissue of mice was quantified by enzyme-linked immunosorbent assay. Expression of Iba1, tumor necrosis factor-α, interleukin-1β and interleukin-6 was significantly lower in the acacetin group compared with the middle cerebral artery occlusion group. Western blot assay results showed that expression of Toll-like receptor 4, nuclear factor kappa B, NLRP3, procaspase-1, caspase-1, pro-interleukin-1β, and interleukin-1β were significantly lower in the acacetin group compared with the middle cerebral artery occlusion group. Our findings indicate that acacetin has a protective effect on cerebral ischemia-reperfusion injury, and its mechanism of action is associated with inhibition of microglia-mediated inflammation and the NLRP3 signaling pathway.展开更多
Minocylcine, a tetracycline derivate, has been shown to cross the blood-brain barrier and enter the central nervous system. In this study, cerebral ischemia-reperfusion injury models were established using the suture ...Minocylcine, a tetracycline derivate, has been shown to cross the blood-brain barrier and enter the central nervous system. In this study, cerebral ischemia-reperfusion injury models were established using the suture method, and minocycline was immediately injected intraperitoneally after cerebral ischemia-repeffusion （22.5 mg/kg, initially 45 mg/kg） at a 12-hour interval. Results showed that after minocycline treatment, the volume of cerebral infarction was significantly reduced, the number of surviving cell in the hippocampal CA1 region increased, the number of apoptotic cells decreased, the expression of caspase-3 and poly（adenosine diphosphate-ribose） polymerase-1 protein was down-regulated, and the escape latency in the water maze test was significantly shortened compared with the ischemia-reperfusion group. Our experimental findings indicate that minocycline can protect against neuronal injury induced by focal ischemia-reperfusion, which may be mediated by the inhibition of caspase-3 and poly（adenosine diphosphate-ribose） polymerase-1 protein expression.展开更多
Objective To study the protective effect of agrimony extracts from different extracting methods on cerebral ischemia-reperfusion injury in rats, in order to optimize the extraction scheme of agrimony.Methods Male rats...Objective To study the protective effect of agrimony extracts from different extracting methods on cerebral ischemia-reperfusion injury in rats, in order to optimize the extraction scheme of agrimony.Methods Male rats were randomly assigned into seven groups: 1. Sham-operated group, 2. Untreated MCAO group (MCAO), 3. Petroleum ether extract of Agrimonia pilosa treated MCAO group (PEA), 4. Ethyl acetate extract of Agrimonia pilosa treated MCAO group (EAEA), 5. Ethanol extract of Agrimonia pilosa treated MCAO group (EEA), 6. Water extract of Agrimonia pilosa treated MCAO group (WEA), 7. Nimodipine treated MCAO group (NP). Intragastrical drug administration (i.g) was performed at 0 and 6 hours after MCAO.Neurological function tests were performed after reperfusion for 24 hours, then the brain was removed for the evaluations of the cerebral infarction volume (percentage of total brain volume) by immunohistochemistry,histological changes (hematoxylin-eosin staining), Na+/K+-ATPase, Ca2+-ATPase (modified method of Svoboda and Mosinger), mRNA expression of Tumor suppressor gene (P53) and hot shock protein (HSP70)(quantitative real-time PCR).Results The neurological function of MCAO group had significantly higher scores than the sham group (P<0.01). The WEA group showed a significantly lower neurological score than the MCAO group (P<0.05),indicating the protective effect of WEA on neurological deficits. The mean infarction volumes of WEA (13.5±6.6%, F=4.75, P<0.01), EEA (19.90±6.90%, F=5.23, P<0.01), PEA (20.40±5.30%, F=4.68,P<0.01) and EAEA (22.50±10.50%, F=6.25, P<0.05) group were all significantly smaller than that of MCAO group (29.40±6.50%). HE staining demonstrated that, compared to the treated groups, the infarcted cerebral tissue of MCAO group had more swelling neural cells, lighter stained nucleus, fewer and irregularly distributed neurons. The activity of Na+/K+-ATPase and Ca2+-ATPase reduced in the MCAO group (3.67±0.48 U/mg,1.28±0.26 U/mg, respectively), and were significantly higher in WEA group (7.56±0.85 U/mg, F=12.65,P=0.010; 3.59±0.22 U/mg, F=8.32, P=0.041, respectively). The MCAO group showed significantly elevated P53 and HSP70 mRNA expressions compared to the sham group (P<0.01, P<0.05). P53 mRNA expressions in Agrimony extracts treated groups were significantly lower than that of the MCAO group (all P<0.01), with the WEA group showing the greatest difference from MCAO group. The HSP70 mRNA level of the treated groups were not significantly different from that of the MCAO group.Conclusions Treatment using water extracts of agrimony can promote the best functional and metabolic recovery for rat model of cerebral ischemia-reperfusion injury, which maybe relate with the upregulation of energy metabolism in nerve cells after MCAO.展开更多
Amyloid 13-peptide, a major component of senile plaques in Alzheimer＇s disease, has been implicated in neuronal cell death and cognitive impairment. Recently, studies have shown that the pathogenesis of cerebral isch...Amyloid 13-peptide, a major component of senile plaques in Alzheimer＇s disease, has been implicated in neuronal cell death and cognitive impairment. Recently, studies have shown that the pathogenesis of cerebral ischemia is closely linked with Alzheimer＇s disease. In this study, a rat model of global cerebral ischemia-reperfusion injury was established via occlusion of four arteries; meanwhile, fibrillar amyloid [3-peptide was injected into the rat lateral ventricle. The Morris water maze test and histological staining revealed that administration of amyloid 13-peptide could further aggravate impairments to learning and memory and neuronal cell death in the hippocampus of rats subjected to cerebral ischemia-reperfusion injury. Western blot showed that phosphorylation of tau protein and the activity of glycogen synthase kinase 313 were significantly stronger in cerebral ischemia-reperfusion injury rats subjected to amyloid [3-peptide administration than those undergo- ing cerebral ischemia-repetfusion or amyloid 13-peptide administration alone. Conversely, the activ- ity of protein phosphatase 2A was remarkably reduced in rats with cerebral ischemia-reperfusion injury following amyloid 13-peptide administration. These findings suggest that amyloid 13-peptide can potentiate tau phosphorylation induced by cerebral ischemia-reperfusion and thereby aggravate cognitive impairment.展开更多
BACKGROUND： Acupuncture treatment on injured cerebral axons has shown to provide efficacy in clinical practice. It is unknown whether acupuncture produces therapeutic effects by protecting injured cerebral myelin in ...BACKGROUND： Acupuncture treatment on injured cerebral axons has shown to provide efficacy in clinical practice. It is unknown whether acupuncture produces therapeutic effects by protecting injured cerebral myelin in ischemic stroke. OBJECTIVE： To test whether acupuncture provides protection for injured cerebral myelin, based on quantitative data from cerebral ischemia-reperfusion rats, and to compare the effects of early and late acupuncture on serum myelin basic protein （MBP） content and remyelination of the ischemic internal capsule.DESIGN, TIME AND SETTING： A randomized, controlled experiment was performed at the Neurobiological Laboratory, Sichuan University from March 2005 to March 2006. MATERIALS： ＂Hua Tuo＂ Brand filiform needles were produced by the Medical Instrument Factory of Suzhou, China.METHODS： A total of 52 adult, healthy, male, Sprague Dawley rats were randomly assigned to four groups： control （n = 4）, model （n = 16）, early acupuncture （n = 16）, and late acupuncture （n = 16）. The focal cerebral ischemia-reperfusion model was established by middle cerebral artery occlusion in the right hemisphere using the modified thread embolism method in the latter three groups. Early and late acupuncture groups underwent acupuncture after ischemia for 30 minutes and 2 hours using the Xingnaokaiqiao needling method, respectively. Acupoints were ＂Neiguarf＇ （PC 6） and ＂Sanyinjiao＂ （SP 6） on the bilateral sides, as well as ＂Shuigou＇ （DU 26） and ＂Baihui＂ （DU 20） with stimulation for 1 minute at each acupoint. Acupuncture at all acupoints was performed two or three times while the needle was retained, once per day. No special handling was administered to the control clroup.MAIN OUTCOME MEASURES： For each group, remyelination of the internal capsule was observed by Pal-Weigert＇s myelin staining and serum MBP content was detected using enzyme-linked immunosorbent assay method on days 1,3, 5, and 7 following ischemia-reperfusion injury.RESULTS： Compared with the control group, massive demyelination of the internal capsule occurred, and serum MBP content increased in the model group （P 〈 0.05）. Compared with the model group, the extent of demyelination in the internal capsule was less distinct and serum MBP content was significantly less in the early and late acupuncture group （P 〈 0.01 ）. Compared with the late acupuncture group, serum MBP content reached a peak later and the peak value was less in the early acupuncture group. CONCLUSION： Results suggest that acupuncture exerts a protective effect on injured cerebral myelin in ischemia-reperfusion rats by reducing serum MBP content and promoting remyelination. The study also suggests that the effect of early acupuncture is superior to late acupuncture.展开更多
BACKGROUND：Studies have reported that potassium channel openers exhibit a protective effect on cerebral ischemia-reperfusion injury and inhibit glutamate excitotoxicity in rats.However,the effects of the glutamate re...BACKGROUND：Studies have reported that potassium channel openers exhibit a protective effect on cerebral ischemia-reperfusion injury and inhibit glutamate excitotoxicity in rats.However,the effects of the glutamate receptor 1α and glutamate transporter 1 remain poorly understood.OBJECTIVE：To investigate the prophylactic use of the adenosine triphosphate-sensitive potassium channel opener cromakalim on neurological function and cerebral infarct size,as well as glutamate receptor 1α and glutamate transporter 1 expression,in rats with cerebral ischemia-reperfusion injury,and to explore action mechanisms underlying reduced glutamate excitotoxicity and neuroprotection in rats.DESIGN,TIME AND SETTING：Randomized,controlled,animal experiment was performed at the Brain Institute,Qingdao University Medical College,Between July 2008 and April 2009.MATERIALS：Cromakalim was purchased from Sigma,USA; rabbit anti-glutamate receptor 1α polyclonal antibody was offered by Wuhan Boster,China; rabbit anti-glutamate transporter 1 polyclonal antibody was offered by Santa Cruz Biotechnology,USA.METHODS：Sixty male,Wistar rats,aged 6 months,were randomly assigned to three groups （n =20）：sham-surgery,model,and cromakalim.Intraluminal thread methods were used to establish middle cerebral artery occlusion in rats from the model and cromakalim groups.Rats from the sham-surgery group were subjected to exposed common carotid artery,external carotid artery,and internal carotid artery,without occlusion.Cromakalim （10 mg/kg） was administered 30 minutes prior to middle cerebral artery occlusion,but there was no intervention in the model and sham-surgery groups.MAIN OUTCOME MEASURES：At 24 hours post-surgery,neurological behavioral functions were evaluated using Bederson＇s test,cerebral infarction volume was determined following tetrazolium chloride staining,and glutamate receptor 1a and glutamate transporter 1 expressions were detected using immunohistochemistry.RESULTS：Following cerebral ischemia-reperfusion injury,neurological behavioral malfunctions were obvious in all mice.Focal cerebral infarction was detected in ischemic hemispheres,glutamate receptor 1α expression increased,and glutamate transporter 1 expression decreased in the ischemic hemisphere （P〈 0.05）.Compared with the model group,neurological behavioral functions significantly improved,cerebral infarction volume was significantly reduced （P〈 0.05）,glutamate receptor 1α expression was significantly decreased,and glutamate transporter 1 expression was increased in the cromakalim group （P 〈 0.05）.CONCLUSION：Improved neurological function and reduced cerebral infarction volume in rats through the preventive use of cromakalim could be related to decreased glutamate receptor 1α expression and enhanced glutamate transporter 1 expression.展开更多
[Objectives] To explore the protective effect of Sanguis Draconis flavones (SDF) on rat focal cerebral ischemia-reperfusion injury (CIRI) models established by middle cerebral artery occlusion (MCAO).[Methods] A total...[Objectives] To explore the protective effect of Sanguis Draconis flavones (SDF) on rat focal cerebral ischemia-reperfusion injury (CIRI) models established by middle cerebral artery occlusion (MCAO).[Methods] A total of 60 healthy adult male Sprague-Dawley rats were selected. They were evenly and randomly divided into sham group, model group, edaravone group (12 mg/kg) and SDF group (360 mg/kg), and administered intragastrically and intraperitoneally. The middle cerebral artery of each rat was blocked by suture-occluded method to establish a CIRI model. After ischemia for 2 h and reperfusion for 48 h, the pathological injury on the ischemic side was observed by HE staining;the neuron and myelin sheath structure was observed by transmission electron microscopy;the expression of G protein-coupled receptor kinase 2 (GRK2) was preserved by immunohistochemistry;and the transfer of GRK2 was detected by western-blot.[Results] After 48 h of CIRI, the nuclei of the penumbral cortical neurons shrank, the chromatin was unevenly distributed, the nuclear membrane was dissolved and the mitochondria in the cytoplasm were swollen and vacuolated. The myelin layer was disordered. With this change, the distribution of GRK2 subcellular cells in the penumbra of the injured lateral cortex transferred from the cytoplasm to the membrane. SDF can effectively restore neuronal and myelin sheath structural damage and reduce the functional (membrane coupling) expression of GRK2.[Conclusions] GRK2 may be an effective target for SDF to protect the impaired blood-brain barrier (BBB) in CIRI.展开更多
OBJECTIVE To investigate the neuroprotective effect of cerebroprotein hydroly⁃sate(CH)on cerebral ischemia-reperfusion injury in mice.METHODS A total of 60 male SPF Kunming mice were randomly divided,reforming longa m...OBJECTIVE To investigate the neuroprotective effect of cerebroprotein hydroly⁃sate(CH)on cerebral ischemia-reperfusion injury in mice.METHODS A total of 60 male SPF Kunming mice were randomly divided,reforming longa method into sham group(sham),model group(tMCAO,reforming longa method),CH 0.2 and 0.5 g·kg-1 groups and positive drug control group(edaravone 0.008 g·kg-1).Neurological deficit score were performed 24 h after opera⁃tion.Mice with scores ranged between 1 and 3 were included in subsequent experiments.Each group had 8 mice.CH edaravone and normal sa⁃line were ip injected for 5 d.The tMCAO group and the sham group were administered the same amount of normal saline as administration groups.TTC staining was used to measure the volume of cerebral infarction;ELISA was per⁃formed to detect the levels of interleukin-6(IL-6),interleukin-1β(IL-1β),brain-derived neurotrophic factor(BDNF)and interferon-γ(IFN-γ)in serum and penumbra.RESULTS TTC staining results showed that there was no infarction in sham group.Compared with tMCAO group,the infarct volume in each administration group was signifi⁃cantly decreased(P<0.01).ELISA results showed that IL-6,IL-1βand IFN-γin serum and penumbra were of significant difference between tMCAO group and sham group(P<0.01),and BDNF was significantly decreased(P<0.01).Compared with tMCAO group,IL-6,IL-1βand IFN-γin serum and ischemic penumbra were sig⁃nificantly decreased in all administration groups(P<0.01),while the content of BDNF was in⁃creased in CH 0.2 g·kg-1 group and edaravone 0.008 g·kg-1 group(P<0.05),and other groups were significantly increased(P<0.01).CONCLU⁃SION CH could reduce the cerebral infarction vol⁃ume and improve the nerve injury caused by cerebral ischemia-reperfusion.The mechanism was related to inhibit the expression of IL-6,IL-1βand IFN-γand increase the expression of BDNF possibly.展开更多
基金supported by Yuan Du Scholars,Clinical Research Center of Affiliated Hospital of Shandong Second Medical University,No.2022WYFYLCYJ02Weifang Key Laboratory,Weifang Science and Technology Development Plan Project Medical Category,No.2022YX093.
文摘The cGAS–STING pathway plays an important role in ischemia-reperfusion injury in the heart,liver,brain,and kidney,but its role and mechanisms in cerebral ischemia-reperfusion injury have not been systematically reviewed.Here,we outline the components of the cGAS–STING pathway and then analyze its role in autophagy,ferroptosis,cellular pyroptosis,disequilibrium of calcium homeostasis,inflammatory responses,disruption of the blood–brain barrier,microglia transformation,and complement system activation following cerebral ischemia-reperfusion injury.We further analyze the value of cGAS–STING pathway inhibitors in the treatment of cerebral ischemia-reperfusion injury and conclude that the pathway can regulate cerebral ischemia-reperfusion injury through multiple mechanisms.Inhibition of the cGAS–STING pathway may be helpful in the treatment of cerebral ischemia-reperfusion injury.
文摘Early or ultra-early pharmacological thrombolysis together with mechanical thrombectomy are key treatments for ischemic stroke,and both are aimed at vascular recanalization and improved collateral circulation.While these methods enhance tissue perfusion in the ischemic penumbra,they also trigger complex neurotoxic reactions,including apoptosis,acidosis,ion imbalance,oxidative stress,and pyroptosis,exacerbating cerebral ischemia-reperfusion injury(CIRI).Pyroptosis,a recently discovered form of programmed cell death driven by inflammation,plays a significant role in neuronal death during CIRI.This study reviews the regulatory mechanisms of pyroptosis in CIRI.
基金Supported by Key Project of Henan Provincial Administration of Traditional Chinese Medicine,No.2017ZY1020General Public Relations Project of Henan Provincial Department of Science and Technology,No.212102311123General Research Project of the National Administration of Traditional Chinese Medicine,No.GZY-KJS-2021-017.
文摘Cerebral ischemia-reperfusion is a process in which the blood supply to the brain is temporarily interrupted and subsequently restored.However,it is highly likely to lead to further aggravation of pathological damage to ischemic tissues or the nervous system.,and has accordingly been a focus of extensive clinical research.As a traditional Chinese medicinal formulation,Sanhua Decoction has gradually gained importance in the treatment of cerebrovascular diseases.Its main constituents include Citrus aurantium,Magnolia officinalis,rhubarb,and Qiangwu,which are primarily used to regulate qi.In the treatment of neurological diseases,the therapeutic effects of the Sanhua Decoction are mediated via different pathways,including antioxidant,anti-inflammatory,and neurotransmitter regu-latory pathways,as well as through the protection of nerve cells and a reduction in cerebral edema.Among the studies conducted to date,many have found that the application of Sanhua Decoction in the treatment of neurological diseases has clear therapeutic effects.In addition,as a natural treatment,the Sanhua Decoction has received widespread attention,given that it is safer and more effective than traditional Western medicines.Consequently,research on the mechanisms of action and efficacy of the Sanhua Decoctions in the treatment of cerebral ischemia-reperfusion injury is of considerable significance.In this paper,we describe the pathogenesis of cerebral ischemia-reperfusion injury and review the current status of its treatment to examine the therapeutic mechanisms of action of the Sanhua Decoction.We hope that the findings of the research presented herein will contribute to a better understanding of the efficacy of this formulation in the treatment of cerebral ischemia-reperfusion,and provide a scientific basis for its application in clinical practice.
文摘Despite improvement in cardiopulmonary resuscitation(CPR)performance,cardiac arrest(CA)is still associated with poor prognosis.The high mortality rate is due to multi-organ dysfunction caused by cerebral ischemia and reperfusion injury(I/R).The guidelines for CPR suggest the use of therapeutic hypothermia(TH)as an effective treatment to decrease mortality and the only approach confirmed to reduce I/R injury.During TH,sedative agents(propofol)and analgesia agents(fentanyl)are commonly used to prevent shiver and pain.However,propofol has been associated with a number of serious adverse effects such as metabolic acidosis,cardiac asystole,myocardial failure,and death.In addition,mild TH alters the pharmacokinetics of agents(propofol and fentanyl)and reduces their systemic clearance.For CA patients undergoing TH,propofol can be overdosed,leading to delayed awakening,prolonged mechanical ventilation,and other subsequent complications.Ciprofol(HSK3486)is a novel anesthetic agent that is convenient and easy to administer intravenously outside the operating room.Ciprofol is rapidly metabolized and accumulates at low concentrations after continuous infusion in a stable circulatory system compared to propofol.Therefore,we hypothesized that treatment with HSK3486 and mild TH after CA could protect the brain and other organs.
基金This research was funded by the National Natural Science Foundation of China(No.81773911,81690263 and 81573616)the Development Project of Shanghai Peak Disciplines-Integrated Medicine(No.20180101).
文摘Cerebral ischemia-reperfusion injury(CI/RI)remains the main cause of disability and death in stroke patients due to lack of effective therapeutic strategies.One of the main issues related to CI/RI treatment is the presence of the blood-brain barrier(BBB),which affects the intracerebral delivery of drugs.Ginkgolide B(GB),a major bioactive component in commercially available products of Ginkgo biloba,has been shown significance in CI/RI treatment by regulating inflammatory pathways,oxidative damage,and metabolic disturbance,and seems to be a candidate for stroke recovery.However,limited by its poor hydrophilicity and lipophilicity,the development of GB preparations with good solubility,stability,and the ability to cross the BBB remains a challenge.Herein,we propose a combinatorial strategy by conjugating GB with highly lipophilic docosahexaenoic acid(DHA)to obtain a covalent complex GB-DHA,which can not only enhance the pharmacological effect of GB,but can also be encapsulated in liposomes stably.The amount of finally constructed Lipo@GB-DHA targeting to ischemic hemisphere was validated 2.2 times that of free solution in middle cerebral artery occlusion(MCAO)rats.Compared to the marketed ginkgolide injection,Lipo@GB-DHA significantly reduced infarct volume with better neurobehavioral recovery in MCAO rats after being intravenously administered both at 2 h and 6 h post-reperfusion.Low levels of reactive oxygen species(ROS)and high neuron survival in vitro was maintained via Lipo@GB-DHA treatment,while microglia in the ischemic brain were polarized from the pro-inflammatory M1 phenotype to the tissue-repairing M2 phenotype,which modulate neuroinflammatory and angiogenesis.In addition,Lipo@GB-DHA inhibited neuronal apoptosis via regulating the apoptotic pathway and maintained homeostasis by activating the autophagy pathway.Thus,transforming GB into a lipophilic complex and loading it into liposomes provides a promising nanomedicine strategy with excellent CI/RI therapeutic efficacy and industrialization prospects.
文摘Stroke remains a worldwide health problem. Salvianolate exerts a protective effect in various mi- crocirculatory disturbance-related diseases, but studies of the mechanisms underlying its protective action have mainly focused on the myocardium, whereas little research has been carried out in brain tissue following ischemia-reperfusion. We assessed the neuroprotective effects of salvianolate in a rat model of cerebral ischemia-reperfusion injury induced using the suture method. At onset and 24 and 48 hours after reperfusion, rats were intraperitoneally injected with salvianolate （18 mg/kg） or saline. Neurological deficit scores at 72 hours showed that the neurological functions of rats that had received salvianolate were significantly better than those of the rats that had received saline. 2,3,5-Triphenyltetrazolium chloride was used to stain cerebral tissue to determine the extent of the infarct area. A significantly smaller infarct area and a significantly lower number of apoptotic cells were observed after treatment with salvianolate compared with the saline treatment. Expression of heat shock protein 22 and phosphorylated protein kinase B in ischemic brain tissue was significantly greater in rats treated with salvianolate compared with rats treated with saline. Our findings suggest that salvianolate provides neuroprotective effects against cerebral ischemia-reperfusion injury by upregulating heat shock protein 22 and phosphorylated protein kinase B expression.
文摘BACKGROUND： The pharmacological effects of aspirin on apoptosis are complex. The underlying mechanisms have not been properly defined. OBJECTIVE： To observe the effect of different doses of aspirin on brain cell apoptosis following focal cerebral iscbemia-reperfusion injury （CIRI） in rats. DESING, TIME AND SETTING： A randomized, controlled, animal experiment, performed at the School of Medicine and Pharmaceutics, Jiangnan University between June and October 2006. MATERIALS： Twenty-six male, adult, Sprague Dawley rats （grade Ⅱ）, weighing 240-290 g, were obtained from Shanghai Experimental Animal Center, Chinese Academy of Sciences. Aspirin was provided by Sigma （USA）. METHODS： The rats were randomly divided into four groups： sham-operation （SO）, CIRI ＋ vehicle, CIRI ＋ aspirin （6 mg/kg）, and CIRI ＋ aspirin （60 mg/kg）. Rats in the lesion groups were intragastrically administrated saline, aspirin （6 mg/kg）, or aspirin （60 mg/kg）, respectively. MAIN OUTCOME MEASURES： The number of pyramidal neurons with normal appearance in the cerebral cortex at 24 mm from the midline; apoptotic cell death as measured by TUNEL; Bcl-2 and Bax protein localization was determined by immunohistochemistry; malondialdehyde （MDA） and super oxidation （SOD） content were determined by biochemistry method; adenosine triphosphate （ATP） content measured by capillary electrophoresis. RESULTS： Following CIRI, the following parameters were altered compared with sham-operated animals： the number of neurons with normal appearance was significantly reduced in the cerebral cortex; the number of apoptotic cells increased; Bax protein expression was enhanced; and the ratio between Bcl-2 and Bax decreased. In addition, MDA content increased significantly, whereas ATP content decreased （P 〈 0.01）. Aspirin ameliorated the loss of healthy pyramidal neurons. Both 6 and 60 mg/kg aspirin increased the ratio between Bcl-2 and Bax, with no significant difference between the treatment groups. In addition, 60 mg/kg aspirin decreased MDA content and increased ATP levels. However, 6 mg/kg aspirin did not have the same effect. CONCLUSION： Aspirin reduced the number of apoptotic cells following CIRI. These results suggest that the neuroprotective mechanism of aspirin could be related to elevated Bcl-2 protein levels or decreased Bax protein expression. The increase in the ratio of Bcl-2 to Bax appears to be a common anti-apoptotic mechanism of aspirin.
基金the National High Technology Program of China (863 Programs), No. 2006AA02A117
文摘We investigated nerve growth factor precursor （proNGF） and mature NGF expression in ischemic and non-ischemic cortices after cerebral ischemia-reperfusion injury. In both ischemic and non-ischemic cortices, proNGF was found to be present in the extracellular space and cytoplasm. In addition, mature NGF was expressed in extracellular space, but with a very low signal. In ischemic cortex only, proNGF was significantly decreased, reaching a minimal level at 1 day. Mature NGF was increased at 4 hours, then reached a minimal level at 3 days. The p75 neurotrophin receptor （p75NTR） was significantly decreased after ischemia, and increased at 3 days after ischemia. These results confirmed that proNGF was the predominant form of NGF during the pathological process of cerebral ischemia-repeffusion injury. In addition, our findings suggest that ischemic injury may influence the conversion of proNGF to mature NGF, and that proNGF/p75NTR may be involved in reperfusion injury.
文摘Penehyclidine hydrochloride can promote microcirculation and reduce vascular permeability. However, the role of penehyclidine hydrochlodde in cerebral ischemia-reperfusion injury remains unclear. In this study, in vivo middle cerebral artery occlusion models were established in experimental rats, and penehyclidine hydrochloride pretreatment was given via intravenous injection prior to model establishment. Tetrazolium chloride, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling and immunohistochemical staining showed that, penehyclidine hydrochloride pretreatment markedly attenuated neuronal histopathological changes in the cortex, hippocampus and striatum, reduced infarction size, increased the expression level of BcI-2, decreased the expression level of caspase-3, and inhibited neuronal apoptosis in rats with cerebral ischemia-reperfusion injury. Xanthine oxidase and thiobarbituric acid chromogenic results showed that penehyclidine hydrochloride upregulated the activity of superoxide dismutase and downregulated the concentration of malondialdehyde in the ischemic cerebral cortex and hippocampus, as well as reduced the concentration of extracellular excitatory amino acids in rats with cerebral ischemia-reperfusion injury. In addition, penehyclidine hydrochloride inhibited the expression level of the NR1 subunit in hippocampal nerve cells in vitro following oxygen-glucose deprivation, as detected by PCR. Experimental findings indicate that penehyclidine hydrochloride attenuates neuronal apoptosis and oxidative stress injury after focal cerebral ischemia-reperfusion, thus exerting a neuroprotective effect.
基金Technological Developing Plan of Science and Technology Bureau of Shandong Province, No. 032050116
文摘BACKGROUND： Somatosensory evoked potential （SEP） has become a method with higher sensitivity and specificity than electroencephalogram in detecting the brain function and the region, range and degree of ischemia. However, the effects of ligustrazine on SEP is still not clear. OBJECTIVE ： To study the protective effects of ligustrazini injection on cerebral ischemia-reperfusion injury.DESIGN： Auto-control study, random grouping.SETTING： Qilu Hospital of Shandong University.MATERIALS： The experiment was completed in the Cerebral Functional Room of Qilu Hospital Affiliated to Shandong University from March 2002 to June 2004. A totally of 24 healthy Harbin rabbits were randomly divided into blank control group （n=8）, model control group （n=8） and ligustrazine treatment group （n=8）. Hydrochloric ligustrazine injection, 40 mg/2 mL each ampoule, was provided by the Third Pharmaceutical Factory of Beijing （certification： 93035236273）. The main component was hydrochloric ligustrazine and the chemical name was 2, 3, 5, 6-tetramethyl pyrazine hydrochloride. METHODS：① Modeling method： The bilateral common carotid artery ligation was adopted to make the model. ② Index of cerebral functional lesion evaluated with SEP during ischemia-reperfusion： DISA 2000C neuromyoeletrometer provided by Dantec Electronics Ltd, Denmark was used to detect SEP. ③ Interventional process： Blank control group： The latencies and amplitudes of SEP were measured before injection with 1.5 mg/kg ligustrazine and at the points of 15 minutes, 20 minutes, 30 minutes, 60 minutes, 90 minutes and 120 minutes after injection. Ligustrazine treatment group： Rabbits were injected with 1.5 mg/kg ligustrazine, and those of model control group were injected the same volume of saline. Thirty minutes later, the bilateral common carotid artery of the rabbits all had been ligated for 30 minutes, and then reperfused for 120 minutes. The latencies and amplitudes of SEP were measured before injection, before ligation, at the points of 1 minute, 5 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes and 30 minutes after ligation, and at the points of 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes, 60 minutes, 90 minutes and 120 minutes after reperfusion.④ Evaluating criteria： Normal values of P-wave latencies and amplitudes were （19.34±3.18） ms and （4.55±1.43）μV. Average value before injection in blank control group and average values before injection, after injection and before ligation in ischemiareperfusion group were regarded as control criteria to evaluate changes of P-wave latencies and amplitudes after experiment. MAIN OUTCOME MEASURES： P-wave latencies and amplitudes of SEP in the three groups.RESULTS ： A total of 24 rabbits were involved in the final analysis without any loss.① Blank control group： The P-wave latencies delayed markedly at each time point after injection. Compared with that before injection, there was a significant difference （P 〈 0.05-0.01）. The P-wave amplitudes did not fluctuate noticeably all the time after injection, but significantly decreased when compared with those before injection （P 〈 0.05-0.01）. ② Ischemia-reperfusion group： The P-wave latencies delayed and amplitudes decreased in the rabbits with cerebral ischemia-reperfusion at all points of time during cerebral ischemia-reperfusion, and there was significant difference when compared with the levels before ischemia （P 〈 0.05）. When ligustrazine was injected, the latencies and amplitudes changed less, and as compared with the levels before ischemia, the difference was not significant （P〉 0.05）.CONCLUSION：① Ligustrazine can inhibit P-wave latencies and amplitudes of SEP of normal rabbits.②Ligustrazine can improve P-wave latencies and amplitudes of SEP of rabbits with cerebral ischemia-reperfusion injury.
基金Liaoning Province Social Development Fund Sustentation Item, No. 99225003
文摘BACKGROUND： HOW to control the effect of oxygen-derived free radicals on development of cerebral injury and cerebral edema is a key factor for treating cerebral ischemia-reperfusion injury. OBJECTIVE： To observe and compare the protective effects, synergistic action and mechanisms of ultrashortwave （USW） and radix salviae miltiorrhizae （RSM） on the focal cerebral ischemia-reperfusion injuries in rats. DESIGN： Randomized controlled animal study SEI-FING： Department of Rehabilitation Medicine, First Hospital affiliated to China Medical University MATERIALS： A total of 160 healthy Wistar rats of both genders and aged 18-20 weeks weighing 250-300 g of clean grade were selected in this study. 5 mL/ampoule RSM injection fluid was produced by the First Pharmaceutical Corporation of Shanghai （batch number： 011019, 0.01 mug）. The USW therapeutic device was produced by Shanghai Electronic Device Factory with the frequency of 40.68 MHz and the maximal export power of 40 W. The first channel of power after modulation was 11 W. METHODS： The experiment was carried out in the Rehabilitation Medicine Department of the First Hospital affiliated to China Medical University from May 2002 to January 2003. Focal ischemia-reperfusion model was established in rats by reversible right middle cerebral artery occlusion with filament. Right cerebral ischemia was for 2 hours and then with 24 hours reperfusion. The scores of neurological deficits were evaluated by 0 to 4 scales. After surgery, 64 successful rats models were divided into four groups according to digital table： control group, USW group, RSM group and RSM ＋ USW group with 16 cases in each group. Rats in control group were intraperitoneally injected with the same volume of saline （0.1 mL/g）; rats in USW group were given small dosage of USW on head for 10 minutes at 6 hours after reperfusion; rats in RSM group were intraperitoneally injected with 0.01 mL/g RSM solution at 30 minutes before reperfusion; rats in RSM ＋ USW group were intraperitoneally injected with 0.01 mL/g RSM parenteral solution at 30 minutes before reperfusion and given small dosage of USW on head for 10 minutes once at 6 hours after reperfusion; sixteen rats in sham operation group did not receive any treatment. All 80 rats were taken brains at 24 hours after reperfusion to measure wet and dry weights to calculate water content： Cerebral water content （%） = （1-dry/wet weight） × 100%. Superoxide dismutase （SOD） activity was measured by hydroxylamine method and malondialdehyde （MDA） content was measured by TBA photometric method. MAIN OUTCOME MEASURES ： Cerebral water content, SOD activity and MDA content RESULTS： All 160 rats except 80 failing in modeling were involved in the final analysis. （① The cerebral water content of left hemisphere made no significant difference （P 〉 0.05）. The cerebral water content of right hemisphere in the control group and the three treatment groups was obviously higher than that of the sham operation group [（81.26±0.77）%, （79.74±0.68）%, （79.76±0.81）%, （79.61±0.79）%, （77.43±0.61）%, P 〈 0.05]. The cerebral water content of right hemisphere in the three treatment groups was obviously lower than that of the control group （P〈 0.05）. There was no significant difference among the three treatment groups （P 〉 0.05）. ② Compared with the control group, SOD activity （right） of the control group decreased obviously （P 〈 0.05）, while MDA content increased obviously （P 〈 0.05）. SOD activity in the three therapeutic groups increased obviously, while MDA content decreased obviously （P 〈 0.05）; there was no significant difference among the three treatment groups （P 〉 0.05）. CONCLUSION： ① USW and RSM therapy have neuroprotective effects against focal cerebral ischemia-reperfusion injuries by means of decreasing cerebral water content and MDA and increasing the activity of SOD. ② Synergistic action was not observed between these two therapeutic methods.
文摘Objective To clarify the effects of repetitive transcranial magnetic stimulation (rTMS) on rat motor cortical excitabi- lity and neurofunction after cerebral ischemia-reperfusion injury. Methods After determined awake resting motor threshold (MT) and motor evoked potentials (MEPs) of right hindlimbs, 20 Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) reperfusion injury, then rTMS were applied to rTMS group (n = 10) at different time, while control group (n = 10) received no stimulation. A week later, MT and MEPs were evaluated again, as well as neurological deficits and infarct volume. The effects of rTMS and MCAO reperfusion injury on these parameters were analyzed. Results After MCAO reperfusion, both MT level and neurological deficit scores increased, distinct focal infarction formed, and latency of MEP elongated. Compared with the control group, the increased extent of MT and neurological scores of rats receiving rTMS were significantly lower (P < 0.05), as well as the infarct volumes reduced significantly(P < 0.05). But MEP was not affected by rTMS obviously. There was a positive linear correlation between postinjury MT and infarct volume (r = 0.64, P < 0.05). Conclusion rTMS may facilitate neurofunction recovery after cerebral ischemia-reperfusion. Postinjury MT could provide prognostic information after MCAO reperfusion injury.
基金supported by the Natural Science Foundation of Xinjiang Uygur Autonomous Region of China,No.2016D01C120(to JB)
文摘Acacetin(5,7-dihydroxy-4′-methoxyflavone), a potential neuroprotective agent, has an inhibitory effect on lipopolysaccharide-induced neuroinflammatory reactions. However, whether acacetin has an effect on inflammatory corpuscle 3(NLRP3) after cerebral ischemia-reperfusion injury has not been fully determined. This study used an improved suture method to establish a cerebral ischemia-reperfusion injury model in C57BL/6 mice. After ischemia with middle cerebral artery occlusion for 1 hour, reperfusion with intraperitoneal injection of 25 mg/kg of acacetin(acacetin group) or an equal volume of saline(0.1 mL/10 g, middle cerebral artery occlusion group) was used to investigate the effect of acacetin on cerebral ischemia-reperfusion injury. Infarct volume and neurological function scores were determined by 2,3,5-triphenyltetrazolium chloride staining and the Zea-Longa scoring method. Compared with the middle cerebral artery occlusion group, neurological function scores and cerebral infarction volumes were significantly reduced in the acacetin group. To understand the effect of acacetin on microglia-mediated inflammatory response after cerebral ischemia-reperfusion injury, immunohistochemistry for the microglia marker calcium adapter protein ionized calcium-binding adaptor molecule 1(Iba1) was examined in the hippocampus of ischemic brain tissue. In addition, tumor necrosis factor-α, interleukin-1β, and interleukin-6 expression in ischemic brain tissue of mice was quantified by enzyme-linked immunosorbent assay. Expression of Iba1, tumor necrosis factor-α, interleukin-1β and interleukin-6 was significantly lower in the acacetin group compared with the middle cerebral artery occlusion group. Western blot assay results showed that expression of Toll-like receptor 4, nuclear factor kappa B, NLRP3, procaspase-1, caspase-1, pro-interleukin-1β, and interleukin-1β were significantly lower in the acacetin group compared with the middle cerebral artery occlusion group. Our findings indicate that acacetin has a protective effect on cerebral ischemia-reperfusion injury, and its mechanism of action is associated with inhibition of microglia-mediated inflammation and the NLRP3 signaling pathway.
基金supported by the National Natural Science Foundation of China, No. 81160157the Key Program of the Science and Technology Department of Guizhou Province, No. SY20093075Nomarch Foundation for Excellent Talents in Science, Technology and Education Field of Guizhou Province, No. 201209
文摘Minocylcine, a tetracycline derivate, has been shown to cross the blood-brain barrier and enter the central nervous system. In this study, cerebral ischemia-reperfusion injury models were established using the suture method, and minocycline was immediately injected intraperitoneally after cerebral ischemia-repeffusion （22.5 mg/kg, initially 45 mg/kg） at a 12-hour interval. Results showed that after minocycline treatment, the volume of cerebral infarction was significantly reduced, the number of surviving cell in the hippocampal CA1 region increased, the number of apoptotic cells decreased, the expression of caspase-3 and poly（adenosine diphosphate-ribose） polymerase-1 protein was down-regulated, and the escape latency in the water maze test was significantly shortened compared with the ischemia-reperfusion group. Our experimental findings indicate that minocycline can protect against neuronal injury induced by focal ischemia-reperfusion, which may be mediated by the inhibition of caspase-3 and poly（adenosine diphosphate-ribose） polymerase-1 protein expression.
基金Fund supported by National Science Foundation of China (NSFC) 81503491,81374053, 81630105.
文摘Objective To study the protective effect of agrimony extracts from different extracting methods on cerebral ischemia-reperfusion injury in rats, in order to optimize the extraction scheme of agrimony.Methods Male rats were randomly assigned into seven groups: 1. Sham-operated group, 2. Untreated MCAO group (MCAO), 3. Petroleum ether extract of Agrimonia pilosa treated MCAO group (PEA), 4. Ethyl acetate extract of Agrimonia pilosa treated MCAO group (EAEA), 5. Ethanol extract of Agrimonia pilosa treated MCAO group (EEA), 6. Water extract of Agrimonia pilosa treated MCAO group (WEA), 7. Nimodipine treated MCAO group (NP). Intragastrical drug administration (i.g) was performed at 0 and 6 hours after MCAO.Neurological function tests were performed after reperfusion for 24 hours, then the brain was removed for the evaluations of the cerebral infarction volume (percentage of total brain volume) by immunohistochemistry,histological changes (hematoxylin-eosin staining), Na+/K+-ATPase, Ca2+-ATPase (modified method of Svoboda and Mosinger), mRNA expression of Tumor suppressor gene (P53) and hot shock protein (HSP70)(quantitative real-time PCR).Results The neurological function of MCAO group had significantly higher scores than the sham group (P<0.01). The WEA group showed a significantly lower neurological score than the MCAO group (P<0.05),indicating the protective effect of WEA on neurological deficits. The mean infarction volumes of WEA (13.5±6.6%, F=4.75, P<0.01), EEA (19.90±6.90%, F=5.23, P<0.01), PEA (20.40±5.30%, F=4.68,P<0.01) and EAEA (22.50±10.50%, F=6.25, P<0.05) group were all significantly smaller than that of MCAO group (29.40±6.50%). HE staining demonstrated that, compared to the treated groups, the infarcted cerebral tissue of MCAO group had more swelling neural cells, lighter stained nucleus, fewer and irregularly distributed neurons. The activity of Na+/K+-ATPase and Ca2+-ATPase reduced in the MCAO group (3.67±0.48 U/mg,1.28±0.26 U/mg, respectively), and were significantly higher in WEA group (7.56±0.85 U/mg, F=12.65,P=0.010; 3.59±0.22 U/mg, F=8.32, P=0.041, respectively). The MCAO group showed significantly elevated P53 and HSP70 mRNA expressions compared to the sham group (P<0.01, P<0.05). P53 mRNA expressions in Agrimony extracts treated groups were significantly lower than that of the MCAO group (all P<0.01), with the WEA group showing the greatest difference from MCAO group. The HSP70 mRNA level of the treated groups were not significantly different from that of the MCAO group.Conclusions Treatment using water extracts of agrimony can promote the best functional and metabolic recovery for rat model of cerebral ischemia-reperfusion injury, which maybe relate with the upregulation of energy metabolism in nerve cells after MCAO.
基金supported by the National High Technology Research and Development Program of China("863"Program),No.2012AA020905the National Natural Science Foundation of China,No.81171143 and30971011+1 种基金National Natural Science Foundation of China(NSFC)/Research Grants Council(RGC) Joint Research Scheme,No.81161160570TsinghuaYue-Yuen Medical Sciences Fund
文摘Amyloid 13-peptide, a major component of senile plaques in Alzheimer＇s disease, has been implicated in neuronal cell death and cognitive impairment. Recently, studies have shown that the pathogenesis of cerebral ischemia is closely linked with Alzheimer＇s disease. In this study, a rat model of global cerebral ischemia-reperfusion injury was established via occlusion of four arteries; meanwhile, fibrillar amyloid [3-peptide was injected into the rat lateral ventricle. The Morris water maze test and histological staining revealed that administration of amyloid 13-peptide could further aggravate impairments to learning and memory and neuronal cell death in the hippocampus of rats subjected to cerebral ischemia-reperfusion injury. Western blot showed that phosphorylation of tau protein and the activity of glycogen synthase kinase 313 were significantly stronger in cerebral ischemia-reperfusion injury rats subjected to amyloid [3-peptide administration than those undergo- ing cerebral ischemia-repetfusion or amyloid 13-peptide administration alone. Conversely, the activ- ity of protein phosphatase 2A was remarkably reduced in rats with cerebral ischemia-reperfusion injury following amyloid 13-peptide administration. These findings suggest that amyloid 13-peptide can potentiate tau phosphorylation induced by cerebral ischemia-reperfusion and thereby aggravate cognitive impairment.
文摘BACKGROUND： Acupuncture treatment on injured cerebral axons has shown to provide efficacy in clinical practice. It is unknown whether acupuncture produces therapeutic effects by protecting injured cerebral myelin in ischemic stroke. OBJECTIVE： To test whether acupuncture provides protection for injured cerebral myelin, based on quantitative data from cerebral ischemia-reperfusion rats, and to compare the effects of early and late acupuncture on serum myelin basic protein （MBP） content and remyelination of the ischemic internal capsule.DESIGN, TIME AND SETTING： A randomized, controlled experiment was performed at the Neurobiological Laboratory, Sichuan University from March 2005 to March 2006. MATERIALS： ＂Hua Tuo＂ Brand filiform needles were produced by the Medical Instrument Factory of Suzhou, China.METHODS： A total of 52 adult, healthy, male, Sprague Dawley rats were randomly assigned to four groups： control （n = 4）, model （n = 16）, early acupuncture （n = 16）, and late acupuncture （n = 16）. The focal cerebral ischemia-reperfusion model was established by middle cerebral artery occlusion in the right hemisphere using the modified thread embolism method in the latter three groups. Early and late acupuncture groups underwent acupuncture after ischemia for 30 minutes and 2 hours using the Xingnaokaiqiao needling method, respectively. Acupoints were ＂Neiguarf＇ （PC 6） and ＂Sanyinjiao＂ （SP 6） on the bilateral sides, as well as ＂Shuigou＇ （DU 26） and ＂Baihui＂ （DU 20） with stimulation for 1 minute at each acupoint. Acupuncture at all acupoints was performed two or three times while the needle was retained, once per day. No special handling was administered to the control clroup.MAIN OUTCOME MEASURES： For each group, remyelination of the internal capsule was observed by Pal-Weigert＇s myelin staining and serum MBP content was detected using enzyme-linked immunosorbent assay method on days 1,3, 5, and 7 following ischemia-reperfusion injury.RESULTS： Compared with the control group, massive demyelination of the internal capsule occurred, and serum MBP content increased in the model group （P 〈 0.05）. Compared with the model group, the extent of demyelination in the internal capsule was less distinct and serum MBP content was significantly less in the early and late acupuncture group （P 〈 0.01 ）. Compared with the late acupuncture group, serum MBP content reached a peak later and the peak value was less in the early acupuncture group. CONCLUSION： Results suggest that acupuncture exerts a protective effect on injured cerebral myelin in ischemia-reperfusion rats by reducing serum MBP content and promoting remyelination. The study also suggests that the effect of early acupuncture is superior to late acupuncture.
基金Shandong Provincial Science and Technology Plan Foundation
文摘BACKGROUND：Studies have reported that potassium channel openers exhibit a protective effect on cerebral ischemia-reperfusion injury and inhibit glutamate excitotoxicity in rats.However,the effects of the glutamate receptor 1α and glutamate transporter 1 remain poorly understood.OBJECTIVE：To investigate the prophylactic use of the adenosine triphosphate-sensitive potassium channel opener cromakalim on neurological function and cerebral infarct size,as well as glutamate receptor 1α and glutamate transporter 1 expression,in rats with cerebral ischemia-reperfusion injury,and to explore action mechanisms underlying reduced glutamate excitotoxicity and neuroprotection in rats.DESIGN,TIME AND SETTING：Randomized,controlled,animal experiment was performed at the Brain Institute,Qingdao University Medical College,Between July 2008 and April 2009.MATERIALS：Cromakalim was purchased from Sigma,USA; rabbit anti-glutamate receptor 1α polyclonal antibody was offered by Wuhan Boster,China; rabbit anti-glutamate transporter 1 polyclonal antibody was offered by Santa Cruz Biotechnology,USA.METHODS：Sixty male,Wistar rats,aged 6 months,were randomly assigned to three groups （n =20）：sham-surgery,model,and cromakalim.Intraluminal thread methods were used to establish middle cerebral artery occlusion in rats from the model and cromakalim groups.Rats from the sham-surgery group were subjected to exposed common carotid artery,external carotid artery,and internal carotid artery,without occlusion.Cromakalim （10 mg/kg） was administered 30 minutes prior to middle cerebral artery occlusion,but there was no intervention in the model and sham-surgery groups.MAIN OUTCOME MEASURES：At 24 hours post-surgery,neurological behavioral functions were evaluated using Bederson＇s test,cerebral infarction volume was determined following tetrazolium chloride staining,and glutamate receptor 1a and glutamate transporter 1 expressions were detected using immunohistochemistry.RESULTS：Following cerebral ischemia-reperfusion injury,neurological behavioral malfunctions were obvious in all mice.Focal cerebral infarction was detected in ischemic hemispheres,glutamate receptor 1α expression increased,and glutamate transporter 1 expression decreased in the ischemic hemisphere （P〈 0.05）.Compared with the model group,neurological behavioral functions significantly improved,cerebral infarction volume was significantly reduced （P〈 0.05）,glutamate receptor 1α expression was significantly decreased,and glutamate transporter 1 expression was increased in the cromakalim group （P 〈 0.05）.CONCLUSION：Improved neurological function and reduced cerebral infarction volume in rats through the preventive use of cromakalim could be related to decreased glutamate receptor 1α expression and enhanced glutamate transporter 1 expression.
基金Supported by Foundation of Anhui Academy of Medical Sciences(YKY2018006)
文摘[Objectives] To explore the protective effect of Sanguis Draconis flavones (SDF) on rat focal cerebral ischemia-reperfusion injury (CIRI) models established by middle cerebral artery occlusion (MCAO).[Methods] A total of 60 healthy adult male Sprague-Dawley rats were selected. They were evenly and randomly divided into sham group, model group, edaravone group (12 mg/kg) and SDF group (360 mg/kg), and administered intragastrically and intraperitoneally. The middle cerebral artery of each rat was blocked by suture-occluded method to establish a CIRI model. After ischemia for 2 h and reperfusion for 48 h, the pathological injury on the ischemic side was observed by HE staining;the neuron and myelin sheath structure was observed by transmission electron microscopy;the expression of G protein-coupled receptor kinase 2 (GRK2) was preserved by immunohistochemistry;and the transfer of GRK2 was detected by western-blot.[Results] After 48 h of CIRI, the nuclei of the penumbral cortical neurons shrank, the chromatin was unevenly distributed, the nuclear membrane was dissolved and the mitochondria in the cytoplasm were swollen and vacuolated. The myelin layer was disordered. With this change, the distribution of GRK2 subcellular cells in the penumbra of the injured lateral cortex transferred from the cytoplasm to the membrane. SDF can effectively restore neuronal and myelin sheath structural damage and reduce the functional (membrane coupling) expression of GRK2.[Conclusions] GRK2 may be an effective target for SDF to protect the impaired blood-brain barrier (BBB) in CIRI.
基金Natural science foundation of Hebei Province(H2020405298)。
文摘OBJECTIVE To investigate the neuroprotective effect of cerebroprotein hydroly⁃sate(CH)on cerebral ischemia-reperfusion injury in mice.METHODS A total of 60 male SPF Kunming mice were randomly divided,reforming longa method into sham group(sham),model group(tMCAO,reforming longa method),CH 0.2 and 0.5 g·kg-1 groups and positive drug control group(edaravone 0.008 g·kg-1).Neurological deficit score were performed 24 h after opera⁃tion.Mice with scores ranged between 1 and 3 were included in subsequent experiments.Each group had 8 mice.CH edaravone and normal sa⁃line were ip injected for 5 d.The tMCAO group and the sham group were administered the same amount of normal saline as administration groups.TTC staining was used to measure the volume of cerebral infarction;ELISA was per⁃formed to detect the levels of interleukin-6(IL-6),interleukin-1β(IL-1β),brain-derived neurotrophic factor(BDNF)and interferon-γ(IFN-γ)in serum and penumbra.RESULTS TTC staining results showed that there was no infarction in sham group.Compared with tMCAO group,the infarct volume in each administration group was signifi⁃cantly decreased(P<0.01).ELISA results showed that IL-6,IL-1βand IFN-γin serum and penumbra were of significant difference between tMCAO group and sham group(P<0.01),and BDNF was significantly decreased(P<0.01).Compared with tMCAO group,IL-6,IL-1βand IFN-γin serum and ischemic penumbra were sig⁃nificantly decreased in all administration groups(P<0.01),while the content of BDNF was in⁃creased in CH 0.2 g·kg-1 group and edaravone 0.008 g·kg-1 group(P<0.05),and other groups were significantly increased(P<0.01).CONCLU⁃SION CH could reduce the cerebral infarction vol⁃ume and improve the nerve injury caused by cerebral ischemia-reperfusion.The mechanism was related to inhibit the expression of IL-6,IL-1βand IFN-γand increase the expression of BDNF possibly.
