The inflammato ry response plays an important role in neuroprotection and regeneration after ischemic insult.The use of non-ste roidal anti-inflammatory drugs has been a matter of debate as to whether they have benefi...The inflammato ry response plays an important role in neuroprotection and regeneration after ischemic insult.The use of non-ste roidal anti-inflammatory drugs has been a matter of debate as to whether they have beneficial or detrimental effects.In this context,the effects of the anti-inflammatory agent meloxicam have been scarcely documented after stro ke,but its ability to inhibit both cyclooxygenase isoforms(1 and 2) could be a promising strategy to modulate postischemic inflammation.This study analyzed the effect of meloxicam in a transient focal cerebral ischemia model in rats,measuring its neuroprotective effect after 48 hours and 7 days of reperfusion and the effects of the treatment on the glial scar and regenerative events such as the generation of new progenitors in the subventricular zone and axonal sprouting at the edge of the damaged area.We show that meloxicam’s neuroprotective effects remained after 7 days of reperfusion even if its administration was restricted to the two first days after ischemia.Moreover,meloxicam treatment modulated glial scar reactivity,which matched with an increase in axonal sprouting.However,this treatment decreased the formation of neuronal progenitor cells.This study discusses the dual role of anti-inflammatory treatments after stro ke and encourages the careful analysis of both the neuroprotective and the regenerative effects in preclinical studies.展开更多
X-box-binding protein-1 (XBP-1) is an essential transcription factor in endoplasmic reticulum stress. In this study, XBP-1 gene-transfected neural stem cells (NSCs) were transplanted into lesion sites to ensure stabil...X-box-binding protein-1 (XBP-1) is an essential transcription factor in endoplasmic reticulum stress. In this study, XBP-1 gene-transfected neural stem cells (NSCs) were transplanted into lesion sites to ensure stability and persistent expression of XBP-1, resulting in the exertion of anti-apoptotic effects. Simultaneously, XBP-1 gene transfection promotes the survival and differentiation of transplanted NSCs. Results from this study demonstrated that survival, proliferation and differentiation of XBP-1 gene-modified NSCs were enhanced when compared to unmodified NSCs at 28 days post-transplantation (P < 0.05). A diminished number of apoptotic neural cells increased Bcl-2 expression and reduced Bax expression, and were observed in the ischemic region of the XBP-1-NSCs group (P < 0.05). These results indicated that modification of the XBP-1 gene enhances the survival and migration of NSCs in vivo and decreases the occurrence of apoptosis.展开更多
Although neuroimaging is commonly utilized to study Wallerian degeneration,it cannot display Wallerian degeneration early after brain injury.In the present study,we attempted to examine pathologically the process of W...Although neuroimaging is commonly utilized to study Wallerian degeneration,it cannot display Wallerian degeneration early after brain injury.In the present study,we attempted to examine pathologically the process of Wallerian degeneration early after brain injury.Cerebral peduncle demyelination was observed at 3 weeks post brain ischemia,followed by demyelination in the cervical enlargement at 6 weeks.Anterograde tracing of the corticospinal tract with biotinylated dextran amine showed that following serious neurologic deficit,the tracing of the corticospinal tract of the internal capsule,cerebral peduncle,and cervical enlargement indicated serious Wallerian degeneration.展开更多
BACKGROUND: Phycocyanin can anti-oxidize and clear free radial. Whether its protective effect on brain is related to Caspase-3, the promoter and operator of apoptosis, is highly concerned. OBJECTIVE: To observe phycoc...BACKGROUND: Phycocyanin can anti-oxidize and clear free radial. Whether its protective effect on brain is related to Caspase-3, the promoter and operator of apoptosis, is highly concerned. OBJECTIVE: To observe phycocyanin for protecting nerve function and reducing the size of cerebral infarction of rats with brain ischemia-reperfusion and its effect on the expression of Caspase-3 mRNA. DESIGN: A randomized controlled experiment. SETTING: Institute of Cerebrovascular Disease, Affiliated Hospital of Medical College of Qingdao University. MATERIALS: Totally 84 adult healthy female Wistar rats, weighing 210 to 250 g, of clean grade, were provided by the Animal Experimental Center of Shandong University. Phycocyanin (Institute of Oceanography of Chinese Academy of Sciences) was used. METHODS: This experiment was carried out in the Key Laboratory for Prevention and Treatment of Brain Diseases during May to December 2005.① The rats were randomized into sham-operation group (n=4), control group (n=40) and phycocyanin-treated group (n=40). Middle cerebral artery occlusion/reperfusion (MACO/R) models were created on the rats of control and phycocyanin-treated groups with suture-occluded method by inserting a thread into left side external-internal carotid artery. In the sham-operation group, inserting suture was omitted. After ischemia for 1 hour and reperfusion for 2 hours, suspension of phycocyanin was intragastrically administrated into the rats of the phycocyanin-treated group at 100 mg/kg , and the same volume of normal saline was isochronously administrated into the rats of control group as the same. ② Six rats were chosen respectively from the control group and phycocyanin-treated group, then neurologic impairment degrees of rats were evaluated according to Bederson’s grading. ③ Six rats were chosen respectively from the control and phycocyanin-treated groups. The isolated brain tissue was stained with triphenyltetrazolium chloride, and then the size of cerebral infarction was calculated with HPIAS-1000 image analytical system by calculating the ratio of cerebral infarction size at each layer and contralateral hemisphere size of the same layer. ④ Twenty-eight rats were chosen respectively from the control and phycocyanin-treated groups. Brain tissue was harvested at reperfusion for 6,12,24 hours and for 2,3,7 and 14 days after ischemia for 1 hour, respectively, 4 rats at each time point. Brain tissue of 4 rats of sham-operation group was harvested at the 24th hour after operation. Brain tissue sections were performed in situ hybridization detection of Caspase-3 mRNA. MAIN OUTCOME MEASURES: Comparison of neurologic impairment degree, cerebral infarction size and the expression of brain tissue Caspase-3 mRNA of rats between two groups. RESULTS: Totally 84 rats entered the stage of result analysis. ① Bederson’s scores at ischemia and reperfusion for 24 and 48 hours were significantly lower in the phycocyanin-treated group than in the control group(P < 0.05). ② After brain ischemia and reperfusion, the infarction area was the largest in the 3rd layer in both control and phycocyanin-treated group, which was(25.23±0.47)% and(23.09±1.20) %, respectively, and the size of infarction area in the 2nd layer to the 5th layer was significantly smaller in the phycocyanin-treated group than in the control group (P < 0.05). ③ Positive cell counts of brain tissue Caspase-3 mRNA: The number of positive cells of Caspase-3 mRNA of control group was increased from cerebral ischemia and reperfusion 6 hours, reached the peak at ischemia and reperfusion 24 hours, began to decrease 2 days later and positive cells of Caspase-3 mRNA were still expressed on the 14th day after reperfusion. At ischemia and reperfusion 6,12 and 24 hours as well as 2,3,7 and 14 days, positive cell counts of Caspase-3 at peripheral ischemic area were significantly lower in the phycocyanin-treated group[(70.67 ±3.65), (85.06±4.79), (119.54±5.37) ,(74.26±2.19), (62.08±3.34), (23.11±1.89), (10.75±2.63) /visual field] than in the control group[(94.38±8.28),(108.81±16.11),(140.88±14.47),(98.13±11.31),(81.03±9.31),(31.22±8.86), (16.06±5.96)/visual field] ( P < 0.05); and those at central ischemic area were also significantly lower in the phycocyanin-treated group [(33.86±4.01),(39.51±3.46),(50.96±2.53),(43.07±4.09),(36.25±3.72),(9.03±3.87),(4.91±5.59)/visual field ]than in the control group[(51.35±2.13),(54.87±3.42),(61.77±4.94),(55.69±6.06),(49.01±5.73),(12.84±3.37),(7.32±2.39)/visual field](P < 0.05). CONCLUSION: Phycocyanin can obviously improve the neurologic function, reduce the size of brain infarction and down-regulate the expression of Caspase-3 mRNA of rats with ischemia and reperfusion injury, thus protect brain.展开更多
<正>BACKGROUND:Numerous studies have shown that magnetic resonance imaging(MRI) can detect survival and migration of super paramagnetic iron oxide-labeled stem cells in models of focal cerebral infarction. OBJEC...<正>BACKGROUND:Numerous studies have shown that magnetic resonance imaging(MRI) can detect survival and migration of super paramagnetic iron oxide-labeled stem cells in models of focal cerebral infarction. OBJECTIVE:To observe distribution of bone marrow mesenchymal stem cells(BMSCs) in a rat model of global brain ischemia following cardiac arrest and resuscitation,and to investigate the feasibility of tracing iron oxide-labeled BMSCs using non-invasive MRI. DESIGN,TIME AND SETTING:The randomized,controlled,molecular imaging study was performed at the Linbaixin Medical Research Center,Second Affiliated Hospital,Sun Yat-sen University,and the Institute of Cardiopulmonary Cerebral Resuscitation,Sun Yat-sen University, China from October 2006 to February 2009. MATERIALS:A total of 40 clean,Sprague Dawley rats,aged 6 weeks and of either gender,were supplied by the Experimental Animal Center,Sun Yat-sen University,China,for isolation of BMSCs. Feridex(iron oxide),Gyroscan Inetra 1.5T MRI system,and cardiopulmonary resuscitation device were used in this study. METHODS:A total of 30 healthy,male Sprague Dawley rats,aged 6 months,were used to induce ventricular fibrillation using alternating current.After 8 minutes,the rats underwent 6-minute chest compression and mechanical ventilation,followed by electric defibrillation,to establish rat models of global brain ischemia due to cardiac arrest and resuscitation.A total of 24 successful models were randomly assigned to Feridex-labeled and non-labeled groups(n=12 for each group).At 2 hours after resuscitation,5×10~6 Feridex-labeled BMSCs,with protamine sulfate as a carrier,and 5×10~6 non-labeled BMSCs were respectively transplanted into both groups of rats through the right carotid artery(cells were harvested in 1 mL phosphate buffered saline). MAIN OUTCOME MEASURES:Feridex-labeled BMSCs were observed by Prussian blue staining and electron microscopy.Signal intensity,celluar viability,and proliferative capacity of BMSCs were measured using MRI,Trypan blue test,and MTT assay,respectively.Distribution of transplanted cells was observed in rats utilizing MRI and Prussian blue staining prior to and 1,3,7,and 14 days after transplantation. RESULTS:Prussian blue staining displayed many blue granules in the Feridex-labeled BMSCs. High density of iron granules was observed in the cytoplasm under electron microscopy.According to MRI results,and compared with the non-labeled group,the signal intensity was decreased in the Feridex-labeled group(P<0.05).The decrease was most significant in the 50μg/mL Feridex-labeled group(P<0.01).There were no significant differences in celluar viability and proliferation of BMSCs between the Feridex-labeled and non-labeled groups after 1 week(P>0.05). Low-signal lesions were detected in the rat hippocampus and temporal cortex at 3 days after transplantation.The low-signal lesions were still detectable at 14 days,and positively stained cells were observed in the hippocampus and temporal cortex using Prussian blue staining.There were no significant differences in signal intensity in the non-labeled group. CONCLUSION:BMSC transplantation traversed the blood-brain barrier and distributed into vulnerable zones in a rat model of cardiac arrest-induced global brain ischemia.MRI provided a non-invasive method to in vivo dynamically and spatially trace Feridex-labeled BMSCs after transplantation.展开更多
The present study established a rat model of focal brain ischemia by occlusion of the middle cerebral artery covered with FeCl3, and investigated the protective effect of 3'-methoxy-puerarin. Hippocampal and corti...The present study established a rat model of focal brain ischemia by occlusion of the middle cerebral artery covered with FeCl3, and investigated the protective effect of 3'-methoxy-puerarin. Hippocampal and cortical c-fos gene expression was determined using in situ hybridization. Results showed that 3'-methoxy-puerarin reduced neurological deficit scores, cerebral infarcted zone and water content of brain tissues, dramatically increased the activity of catalase and glutathione peroxidase in the ischemia zone of the hippocampus, increased the activity of catalase in the cortex, decreased lipid peroxide and lactic acid contents in the hippocampus and cerebral cortex, and down-regulated c-fos gene expression in brain ischemic rats. Results demonstrated that 3'-methoxy-puerarin exhibited cerebroprotective effects against focal brain ischemia, which involved c-fos gene expression.展开更多
Transient brain ischemia has been shown to induce hyperphosphorylation of the microtubule-associated protein tau.To further determine the mechanisms underlying these processes,we investigated the interaction between t...Transient brain ischemia has been shown to induce hyperphosphorylation of the microtubule-associated protein tau.To further determine the mechanisms underlying these processes,we investigated the interaction between tau,glycogen synthase kinase(GSK)-3βand protein phosphatase 2A.The results confirmed that tau protein was dephosphorylated during brain ischemia;in addition,the activity of GSK-3βwas increased and the activity of protein phosphatase2A was decreased.After reperfusion,tau protein was hyperphosphorylated,the activity of GSK-3βwas decreased and the activity of protein phosphatase 2A remained low.Importantly,the interaction of tau with GSK-3βand protein phosphatase 2A was altered during ischemia and reperfusion Lithium chloride could affect tau phosphorylation by regulating the interaction of tau with GSK-3βand protein phosphatase 2A,and improve learning and memory ability of rats after transient brain ischemia.The present study demonstrated that it was the interaction of tau with GSK-3βand protein phosphatase 2A,rather than their individual activities,that dominates the phosphorylation of tau in transient brain ischemia.Hyperphosphorylated tau protein may play an important role in the evolution of brain injury in ischemic stroke.The neuroprotective effects of lithium chloride partly depend on the inhibition of tau phosphorylation during transient brain ischemia.展开更多
The traditional Chinese herb Astragalus membranaceus is a well-known treatment for neurological diseases and is considered to exhibit anti-dementia properties.This study investigated the synergistic effects of magnesi...The traditional Chinese herb Astragalus membranaceus is a well-known treatment for neurological diseases and is considered to exhibit anti-dementia properties.This study investigated the synergistic effects of magnesium ions and Astragalus membranaceus on global brain ischemia in rats.4'-6-diamidino-2-phenylindole staining demonstrated that the number of living neurons was significantly greater in the rat hippocampus after administration of a combination of Astragalus membranaceus and magnesium,compared with a vehicle group,an Astragalus membranaceus alone group,and a magnesium alone group.Western blot assay revealed that cleaved Caspase-3 protein expression was significantly reduced in the rat hippocampus in the combined Astragalus membranaceus and magnesium group compared with the Astragalus membranaceus alone group and the magnesium alone group.The results suggested that the combination of Astragalus membranaceus and magnesium exhibits a stronger neuroprotective effect on global brain ischemia in rats compared with Astragalus membranaceus or magnesium alone.This effect was associated with decreased Caspase-3 expression.展开更多
Ischemic stroke and irreversible consequences:Ischemic stroke in humans is the second most common cause of death in the world(Mozaffarian et al.,2016).The outcomes after a stroke are often dependent on complications,i...Ischemic stroke and irreversible consequences:Ischemic stroke in humans is the second most common cause of death in the world(Mozaffarian et al.,2016).The outcomes after a stroke are often dependent on complications,including motor disorders,depression and dementia(Pluta et al.,2018a),which causes a high risk of re-hospitalization and/or palliative care.This is also the main reason for long-term disability in people after stroke,with up to half of those who survived the stroke will not regain their independence until the end of their lives(Mozaffarian et al.,2016).According to epidemiological forecasts,human ischemic stroke will soon become the dominant cause of death worldwide(Bejot et al.,2016)as well as dementia with the phenotype of Alzheimer’s disease(AD;Kim and Lee 2018).It is suggested that human ischemic stroke and experimental brain ischemia in animals are associated with the possible development of AD neuropathology(Pluta et al.,2018a).展开更多
A rat model of diabetes mellitus was induced by a high fat diet,followed by focal brain ischemia induced using the thread method after 0.5 month.Immunohistochemistry showed that expression of receptor for advanced gly...A rat model of diabetes mellitus was induced by a high fat diet,followed by focal brain ischemia induced using the thread method after 0.5 month.Immunohistochemistry showed that expression of receptor for advanced glycation end-products was higher in the ischemic cortex of diabetic rats compared with non-diabetic rats with brain ischemia.Western blot assay revealed increased phosphorylated c-Jun N-terminal kinase expression,and unchanged phosphorylated extracellular signal-regulated protein kinase protein expression in the ischemic cortex of diabetic rats compared with non-diabetic rats with brain ischemia.Additionally,phosphorylated p38 mitogen-activated protein kinase protein was not detected in any rats in the two groups.Severity of limb hemiplegia was worse in diabetic rats with brain ischemia compared with ischemia alone rats.The results suggest that increased expression of receptor for advanced glycation end-products can further activate the c-Jun N-terminal kinase pathway in mitogen-activated protein kinase,thereby worsening brain injury associated with focal brain ischemia in diabetic rats.展开更多
An update of the etiology of Alzheimer's disease(AD):The current theory of the etiology of AD and the guidelines for most of the wide-ranging treatments activities are built around amyloid and tau protein as causa...An update of the etiology of Alzheimer's disease(AD):The current theory of the etiology of AD and the guidelines for most of the wide-ranging treatments activities are built around amyloid and tau protein as causative agents of the disease(Atlante et al.,2020).At present,based on a comprehensive evaluation of existing and contemporary studies,important questions arise regarding the causal role of amyloid and tau protein in the pathogenesis of AD(Morris et al.,2018).Analyzes of the available evidence does not allow obvious conclusion that amyloid,and especially tau protein,plays a key role in the etiology of AD(Morris et al.,2018).展开更多
We have previously reported that sequential common artery sectioning (SCAS) in mice produces a reproducible pattern of mortality, extensive brain damage and a wide range of measurable neurobehavioral alterations that ...We have previously reported that sequential common artery sectioning (SCAS) in mice produces a reproducible pattern of mortality, extensive brain damage and a wide range of measurable neurobehavioral alterations that include motor incoordination and forelimb flexion. The present study describes a comprehensive method to assess motor functional outcome after brain ischemia produced by SCAS using swimming behavior. We found that after the second artery occlusion the time for completion of the swimming task significantly increased and the swimming pattern alterations observed in the ischemic mice showed no evidence of recovery (up to 96 h). We view the swimming performance strategy described here as a sensitive, simple and economic procedure to assess motor performance after brain ischemia.展开更多
Despite obvious progress in the treatment of acute forms of ischemic stroke, the risk of this condition remains unacceptably high. Brain infarction in the middle cerebral artery basin occurs in patients with atheroscl...Despite obvious progress in the treatment of acute forms of ischemic stroke, the risk of this condition remains unacceptably high. Brain infarction in the middle cerebral artery basin occurs in patients with atherosclerosis. The onset of the brain infarction is facilitated by the cessation of circulation (embolism) in conditions of insufficient collateral circulation. The extent of the infarct zone is determined by neuronal death and impaired microcirculation. The development of new methods for effective targeted restorative stroke therapy is crucial for restorative treatment and reducing the risk of mortality after stroke. Remote ischemic conditioning (RIC) is an approach to limiting reperfusion injury in the ischemic region of the brain after focal ischemia. One of the most commonly used <i>in vivo</i> models in stroke studies is the filament model of Middle Cerebral Artery Occlusion (MCAO) in rats. In our experiment, it was performed for 30 min (J. Koizumi) with subsequent 48-hour reperfusion. Within the first 24 hours after the start of reperfusion several short episodes of ischemia in low limbs were induced. After 48 hours of reperfusion the brains were harvested and stained with TTC. Then we evaluated the effect of RIC within 24 hours <i>ex vivo</i> in rats’ brains, as well as syndecan-1 plasma concentration. Infarct area was assessed by means of Image-Pro program with statistical analysis. Infarct volumes in the model group (31.97% ± 2.5%) were significantly higher compared to the values in the RIC group 48 hours after ischemia-reperfusion (13.6% ± 1.3%) (*P < 0.05). A significant reduction in the area of infarction after RIC is likely due to the effect on the regulation of collateral blood flow in the ischemia area. On the second day after ischemia-reperfusion, tissue swelling was reduced in the RIC group compared to the model group. Analysis of the average concentration of Syndecan-1 revealed the difference between model and RIC groups. Syndecan-1, endothelial glycocalyx protein, might be the regulator which performs vascular control of the interaction with inflammatory cell and is responsible for mediate effect of remote ischemic conditioning on the restriction of ischemic-reperfusion injury.展开更多
Objective： To observe effects of Panax Notoginseng Saponin （PSN） on the expression of Vascular Endothelial Growth Factor （VEGF） after the brain ischemia-reperfusion injury in rats. Methods： 48 SD rats had been r...Objective： To observe effects of Panax Notoginseng Saponin （PSN） on the expression of Vascular Endothelial Growth Factor （VEGF） after the brain ischemia-reperfusion injury in rats. Methods： 48 SD rats had been randomly divided into 4 groups： the sham operation group, the model group, Panax Notoginseng Saponin （PNS） group and Nimodipine group （n=12） . The rats had been treated with PNS, and 7 days later the rat focal cerebral ischemia-reperfusion models had been pre- pared. Neurobehavioral scores （NBS） had been evaluated in each group, TTC staining observed; the immunohistochemistry was used to observe VEGF and mRNA expressions. Results： PNS could not only improve significantly neurobehavioral scores and decrease dramatically cerebral infarct volume, but also increase remarkably VEGF and mRNA expression levels. Conclusion： The PNS is beneficial for rehabilitation after cerebral ischemia reperfusion injury via effectively up-regulating the injured cor- tical VEGF mRNA expression concentrations, which promotes vascular reborn in the ischemic region.展开更多
Objective: To investigate the relationship between p53, p21 proteins and delayed neuronal death (DND) after reperfusion following forebrain ischemia in rats. Methods With four-vessel occlusion model of rats, the expre...Objective: To investigate the relationship between p53, p21 proteins and delayed neuronal death (DND) after reperfusion following forebrain ischemia in rats. Methods With four-vessel occlusion model of rats, the expression of p53, p21 proteins in brain tissue using labeled streptavindin-biotin immunohistochemical (LAAB) suming were observed. Re sults: The expression of p53, p21 proteins in brain was upregulated after reperfusion following 15 min forebrain ischemia and their distribution was similar. p53 and p21 proteins in brian sections was detected earlier in the white matter of hippocampal formation, thalamus, hypothalamus (6 h following reperfusion) than in the neuronal nuclei in cerebral cortex and CA1 region (24h), and the maximal induction was observed at 72 h following reperfusion. CA1 region suffered the most serious injury, where the positive expression of p53 and off proteins was most. Conclusion: Reperfusion following forebrain ischemia could upregulate the expression of p53 and p21 proteins in the brain region, suggesting that p53 and p21 proteins participate in and possibly promote the apoptosis of ’DND.展开更多
In the present study, we hypothesized that 5-hydroxymethyl-2-furfural could attenuate ischemic brain damage by reducing oxidative injury. Thus, mice were subjected to bilateral common carotid artery occlusion to estab...In the present study, we hypothesized that 5-hydroxymethyl-2-furfural could attenuate ischemic brain damage by reducing oxidative injury. Thus, mice were subjected to bilateral common carotid artery occlusion to establish a model of permanent forebrain ischemia. The mice were intraperitoneally injected with 5-hydroxymethyl-2-furfural 30 minutes before ischemia or 5 minutes after ischemia. The survival time of mice injected with 5-hydroxymethyl-2-furfural was longer compared with untreated mice. The mice subjected to ischemia for 30 minutes and reperfusion for 5 minutes were intraperitoneally injected with 5-hydroxymethyl-2-furfural 5 minutes prior to reperfusion, which increased superoxide dismutase content and reduced malondialdehyde content, similar to the effects of Edaravone, a hydroxyl radical scavenger used for the treatment of stroke. These findings indicate that intraperitoneal injection of 5-hydroxymethyl-2-furfural can prolong the survival of mice with permanent forebrain ischemia. This outcome may be mediated by its antioxidative effects.展开更多
Recent evidence exists that glucose transporter 3(GLUT3) plays an important role in the energy metabolism in the brain.Most previous studies have been conducted using focal or hypoxic ischemia models and have focused ...Recent evidence exists that glucose transporter 3(GLUT3) plays an important role in the energy metabolism in the brain.Most previous studies have been conducted using focal or hypoxic ischemia models and have focused on changes in GLUT3 expression based on protein and m RNA levels rather than tissue levels.In the present study,we observed change in GLUT3 immunoreactivity in the adult gerbil hippocampus at various time points after 5 minutes of transient forebrain ischemia.In the sham-operated group,GLUT3 immunoreactivity in the hippocampal CA1 region was weak,in the pyramidal cells of the CA1 region increased in a time-dependent fashion 24 hours after ischemia,and in the hippocampal CA1 region decreased significantly between 2 and 5 days after ischemia,with high level of GLUT3 immunoreactivity observed in the CA1 region 10 days after ischemia.In a double immunofluorescence study using GLUT3 and glial-fibrillary acidic protein(GFAP),we observed strong GLUT3 immunoreactivity in the astrocytes.GLUT3 immunoreactivity increased after ischemia and peaked 7 days in the dentate gyrus after ischemia/reperfusion.In a double immunofluorescence study using GLUT3 and doublecortin(DCX),we observed low level of GLUT3 immunoreactivity in the differentiated neuroblasts of the subgranular zone of the dentate gyrus after ischemia.GLUT3 immunoreactivity in the sham-operated group was mainly detected in the subgranular zone of the dentate gyrus.These results suggest that the increase in GLUT3 immunoreactivity may be a compensatory mechanism to modulate glucose level in the hippocampal CA1 region and to promote adult neurogenesis in the dentate gyrus.展开更多
Objective\ Exploring the alteration of glucocorticoid receptor (GCR) following forebrain ischemia in gerbils. Methods\ Establish a brain ischemia model by occluding bilateral common carotid. The GCR concentrations in ...Objective\ Exploring the alteration of glucocorticoid receptor (GCR) following forebrain ischemia in gerbils. Methods\ Establish a brain ischemia model by occluding bilateral common carotid. The GCR concentrations in forebrain tissue cytosol were detected by radioligand binding assay. The plasma concentrations of cortisol were determined by the method of competitive protein binding analysis. Results\ GCR concentrations had no significant change after 10 min ischemia (P>0 05), while decreased significantly in 1 h ischemia (P<0.01), and reduced more severely in 1 h ischemia followed by 3 h reperfusion (P<0.01). Plasma cortisol increased markedly in 10 min ischemia and 1 h ischemia (P<0.001), while decreased in 1 h ischemia followed by 3 h reperfusion. Conclusion\ GCR concentrations in brain decreased following forebrain ischemia in gerbil.展开更多
BACKGROUND:Pharmacological studies have demonstrated that compound preparation Tongqiao Jiannao capsules composed of Zexie, Baizhu, Honghua, Danshen, and Shexiang can supplement qi, activate blood circulation, relieve...BACKGROUND:Pharmacological studies have demonstrated that compound preparation Tongqiao Jiannao capsules composed of Zexie, Baizhu, Honghua, Danshen, and Shexiang can supplement qi, activate blood circulation, relieve blood stasis, induce resuscitation for alleviating pain, relieve pain, and dilate blood vessels. OBJECTIVE: To observe the effects of Tongqiao Jiannao capsules on the levels of the anti-apoptotic protein Bcl-2 and the proapoptotic protein Bax, and verify the mechanism of action. DESIGN, TIME AND SETTING: Randomized, controlled animal experiment, performed in the Laboratory of Biochemistry and Molecular Biology, Shanxi Medical University between June 2001 and December 2002. MATERIALS: The right middle cerebral arteries of 24 healthy adult Sprague Dawley rats were occluded by the suture method. The primary Chinese herbal medicinal ingredients of Tongqiao Jiannao capsules are Zexie, Baizhu, Honghua, Danshen, and Shexiang, which were purchased from Shanxi Provincial Medicinal Material Company, China, and prepared into condensed granules in the Room for Chinese Herbal Medicine Preparation, Second Hospital, Shanxi Medical University. Bcl-2 and Bax immunohistochemical staining kits, a 3,3-diaminobenzidine(DAB) kit, and an in situ apoptosis detection kit were purchased from Wuhan Boster Bioengineering Co., Ltd., China. METHODS: Twenty-four rats were randomly and evenly divided into three groups: (1) sham-operated rats in which sutures were inserted and immediately pulled out; (2) Tongqiao Jiannao capsule-treated rats that were intragastrically administered 6.5 g/kg/d Tongqiao Jiannao capsule preparation for seven successive days prior to middle cerebral artery occlusion (MCAO); and (3) MCAO rats without any other treatments. MAIN OUTCOME MEASURES: The levels of neural cell apoptosis and Bcl-2 and Bax proteins at 24 hours post-surgery. RESULTS: In the MCAO group, the numbers of apoptotic cells and Bax-positive cells were significantly increased, while the numbers of Bcl-2-positive cells were slightly decreased compared with the sham-operated group. Bcl-2- and Bax-positive cells and apoptotic cells were primarily distributed in the ischemic penumbra. In the Tongqiao Jiannao capsule-treated group, neuronal apoptosis was inhibited, and the number of Bcl-2-positive cells was significantly increased (P < 0.01), while the number of Bax-positive cells was significantly decreased (P < 0.01), compared with the MCAO group. CONCLUSION: Tongqiao Jiannao capsules elevated Bcl-2 expression, lowered Bax expression, and inhibited cellular apoptosis during the process of cerebral ischemia/reperfusion injury.展开更多
Honokiol(HK)usage is greatly restricted by its poor aqueous solubility and limited oral bioavailability.We synthesized and characterized a novel phosphate prodrug of honokiol(HKP)for in vitro and in vivo use.HKP great...Honokiol(HK)usage is greatly restricted by its poor aqueous solubility and limited oral bioavailability.We synthesized and characterized a novel phosphate prodrug of honokiol(HKP)for in vitro and in vivo use.HKP greatly enhanced the aqueous solubility of HK(127.54±15.53 mg/ml)and the stability in buffer solution was sufficient for intravenous administration.The enzymatic hydrolysis of HKP to HK was extremely rapid in vitro(T 1/2=8.9±2.11 s).Pharmacokinetics studies demonstrated that after intravenous administration of HKP(32 mg/kg),HKP was converted rapidly to HK with a time to reach the maximum plasma concentration of^5 min.The prodrug HKP achieved an improved T 1/2(7.97±1.30 h)and terminal volume of distribution(26.02±6.04 ml/kg)compared with direct injection of the equimolar parent drug(0.66±0.01 h)and(2.90±0.342 ml/kg),respectively.Furthermore,oral administration of HKP showed rapid and improved absorption compared with the parent drug.HKP was confirmed to maintain the bioactivity of the parent drug for ameliorating ischemia-reperfusion injury by decreasing brain infarction and improving neurologic function.Taken together,HKP is a potentially useful aqueous-soluble prodrug with improved pharmacokinetic properties which may merit further development as a potential drug candidate.展开更多
基金supported by MINECO and FEDER funds:ref CPP2021-008855 and RTC-2015-4094-1,Junta de Castilla y León ref.LE025P1 7Neural Therapies SLref.NTDev-01 (all to AFL and JMGO)。
文摘The inflammato ry response plays an important role in neuroprotection and regeneration after ischemic insult.The use of non-ste roidal anti-inflammatory drugs has been a matter of debate as to whether they have beneficial or detrimental effects.In this context,the effects of the anti-inflammatory agent meloxicam have been scarcely documented after stro ke,but its ability to inhibit both cyclooxygenase isoforms(1 and 2) could be a promising strategy to modulate postischemic inflammation.This study analyzed the effect of meloxicam in a transient focal cerebral ischemia model in rats,measuring its neuroprotective effect after 48 hours and 7 days of reperfusion and the effects of the treatment on the glial scar and regenerative events such as the generation of new progenitors in the subventricular zone and axonal sprouting at the edge of the damaged area.We show that meloxicam’s neuroprotective effects remained after 7 days of reperfusion even if its administration was restricted to the two first days after ischemia.Moreover,meloxicam treatment modulated glial scar reactivity,which matched with an increase in axonal sprouting.However,this treatment decreased the formation of neuronal progenitor cells.This study discusses the dual role of anti-inflammatory treatments after stro ke and encourages the careful analysis of both the neuroprotective and the regenerative effects in preclinical studies.
文摘X-box-binding protein-1 (XBP-1) is an essential transcription factor in endoplasmic reticulum stress. In this study, XBP-1 gene-transfected neural stem cells (NSCs) were transplanted into lesion sites to ensure stability and persistent expression of XBP-1, resulting in the exertion of anti-apoptotic effects. Simultaneously, XBP-1 gene transfection promotes the survival and differentiation of transplanted NSCs. Results from this study demonstrated that survival, proliferation and differentiation of XBP-1 gene-modified NSCs were enhanced when compared to unmodified NSCs at 28 days post-transplantation (P < 0.05). A diminished number of apoptotic neural cells increased Bcl-2 expression and reduced Bax expression, and were observed in the ischemic region of the XBP-1-NSCs group (P < 0.05). These results indicated that modification of the XBP-1 gene enhances the survival and migration of NSCs in vivo and decreases the occurrence of apoptosis.
文摘Although neuroimaging is commonly utilized to study Wallerian degeneration,it cannot display Wallerian degeneration early after brain injury.In the present study,we attempted to examine pathologically the process of Wallerian degeneration early after brain injury.Cerebral peduncle demyelination was observed at 3 weeks post brain ischemia,followed by demyelination in the cervical enlargement at 6 weeks.Anterograde tracing of the corticospinal tract with biotinylated dextran amine showed that following serious neurologic deficit,the tracing of the corticospinal tract of the internal capsule,cerebral peduncle,and cervical enlargement indicated serious Wallerian degeneration.
文摘BACKGROUND: Phycocyanin can anti-oxidize and clear free radial. Whether its protective effect on brain is related to Caspase-3, the promoter and operator of apoptosis, is highly concerned. OBJECTIVE: To observe phycocyanin for protecting nerve function and reducing the size of cerebral infarction of rats with brain ischemia-reperfusion and its effect on the expression of Caspase-3 mRNA. DESIGN: A randomized controlled experiment. SETTING: Institute of Cerebrovascular Disease, Affiliated Hospital of Medical College of Qingdao University. MATERIALS: Totally 84 adult healthy female Wistar rats, weighing 210 to 250 g, of clean grade, were provided by the Animal Experimental Center of Shandong University. Phycocyanin (Institute of Oceanography of Chinese Academy of Sciences) was used. METHODS: This experiment was carried out in the Key Laboratory for Prevention and Treatment of Brain Diseases during May to December 2005.① The rats were randomized into sham-operation group (n=4), control group (n=40) and phycocyanin-treated group (n=40). Middle cerebral artery occlusion/reperfusion (MACO/R) models were created on the rats of control and phycocyanin-treated groups with suture-occluded method by inserting a thread into left side external-internal carotid artery. In the sham-operation group, inserting suture was omitted. After ischemia for 1 hour and reperfusion for 2 hours, suspension of phycocyanin was intragastrically administrated into the rats of the phycocyanin-treated group at 100 mg/kg , and the same volume of normal saline was isochronously administrated into the rats of control group as the same. ② Six rats were chosen respectively from the control group and phycocyanin-treated group, then neurologic impairment degrees of rats were evaluated according to Bederson’s grading. ③ Six rats were chosen respectively from the control and phycocyanin-treated groups. The isolated brain tissue was stained with triphenyltetrazolium chloride, and then the size of cerebral infarction was calculated with HPIAS-1000 image analytical system by calculating the ratio of cerebral infarction size at each layer and contralateral hemisphere size of the same layer. ④ Twenty-eight rats were chosen respectively from the control and phycocyanin-treated groups. Brain tissue was harvested at reperfusion for 6,12,24 hours and for 2,3,7 and 14 days after ischemia for 1 hour, respectively, 4 rats at each time point. Brain tissue of 4 rats of sham-operation group was harvested at the 24th hour after operation. Brain tissue sections were performed in situ hybridization detection of Caspase-3 mRNA. MAIN OUTCOME MEASURES: Comparison of neurologic impairment degree, cerebral infarction size and the expression of brain tissue Caspase-3 mRNA of rats between two groups. RESULTS: Totally 84 rats entered the stage of result analysis. ① Bederson’s scores at ischemia and reperfusion for 24 and 48 hours were significantly lower in the phycocyanin-treated group than in the control group(P < 0.05). ② After brain ischemia and reperfusion, the infarction area was the largest in the 3rd layer in both control and phycocyanin-treated group, which was(25.23±0.47)% and(23.09±1.20) %, respectively, and the size of infarction area in the 2nd layer to the 5th layer was significantly smaller in the phycocyanin-treated group than in the control group (P < 0.05). ③ Positive cell counts of brain tissue Caspase-3 mRNA: The number of positive cells of Caspase-3 mRNA of control group was increased from cerebral ischemia and reperfusion 6 hours, reached the peak at ischemia and reperfusion 24 hours, began to decrease 2 days later and positive cells of Caspase-3 mRNA were still expressed on the 14th day after reperfusion. At ischemia and reperfusion 6,12 and 24 hours as well as 2,3,7 and 14 days, positive cell counts of Caspase-3 at peripheral ischemic area were significantly lower in the phycocyanin-treated group[(70.67 ±3.65), (85.06±4.79), (119.54±5.37) ,(74.26±2.19), (62.08±3.34), (23.11±1.89), (10.75±2.63) /visual field] than in the control group[(94.38±8.28),(108.81±16.11),(140.88±14.47),(98.13±11.31),(81.03±9.31),(31.22±8.86), (16.06±5.96)/visual field] ( P < 0.05); and those at central ischemic area were also significantly lower in the phycocyanin-treated group [(33.86±4.01),(39.51±3.46),(50.96±2.53),(43.07±4.09),(36.25±3.72),(9.03±3.87),(4.91±5.59)/visual field ]than in the control group[(51.35±2.13),(54.87±3.42),(61.77±4.94),(55.69±6.06),(49.01±5.73),(12.84±3.37),(7.32±2.39)/visual field](P < 0.05). CONCLUSION: Phycocyanin can obviously improve the neurologic function, reduce the size of brain infarction and down-regulate the expression of Caspase-3 mRNA of rats with ischemia and reperfusion injury, thus protect brain.
基金the National Natural Science Foundation of China,No.30801081, 30870691,30700303the New Teacher Foundation of Doctor Center of Ministry of Education of China,No. 200805581179
文摘<正>BACKGROUND:Numerous studies have shown that magnetic resonance imaging(MRI) can detect survival and migration of super paramagnetic iron oxide-labeled stem cells in models of focal cerebral infarction. OBJECTIVE:To observe distribution of bone marrow mesenchymal stem cells(BMSCs) in a rat model of global brain ischemia following cardiac arrest and resuscitation,and to investigate the feasibility of tracing iron oxide-labeled BMSCs using non-invasive MRI. DESIGN,TIME AND SETTING:The randomized,controlled,molecular imaging study was performed at the Linbaixin Medical Research Center,Second Affiliated Hospital,Sun Yat-sen University,and the Institute of Cardiopulmonary Cerebral Resuscitation,Sun Yat-sen University, China from October 2006 to February 2009. MATERIALS:A total of 40 clean,Sprague Dawley rats,aged 6 weeks and of either gender,were supplied by the Experimental Animal Center,Sun Yat-sen University,China,for isolation of BMSCs. Feridex(iron oxide),Gyroscan Inetra 1.5T MRI system,and cardiopulmonary resuscitation device were used in this study. METHODS:A total of 30 healthy,male Sprague Dawley rats,aged 6 months,were used to induce ventricular fibrillation using alternating current.After 8 minutes,the rats underwent 6-minute chest compression and mechanical ventilation,followed by electric defibrillation,to establish rat models of global brain ischemia due to cardiac arrest and resuscitation.A total of 24 successful models were randomly assigned to Feridex-labeled and non-labeled groups(n=12 for each group).At 2 hours after resuscitation,5×10~6 Feridex-labeled BMSCs,with protamine sulfate as a carrier,and 5×10~6 non-labeled BMSCs were respectively transplanted into both groups of rats through the right carotid artery(cells were harvested in 1 mL phosphate buffered saline). MAIN OUTCOME MEASURES:Feridex-labeled BMSCs were observed by Prussian blue staining and electron microscopy.Signal intensity,celluar viability,and proliferative capacity of BMSCs were measured using MRI,Trypan blue test,and MTT assay,respectively.Distribution of transplanted cells was observed in rats utilizing MRI and Prussian blue staining prior to and 1,3,7,and 14 days after transplantation. RESULTS:Prussian blue staining displayed many blue granules in the Feridex-labeled BMSCs. High density of iron granules was observed in the cytoplasm under electron microscopy.According to MRI results,and compared with the non-labeled group,the signal intensity was decreased in the Feridex-labeled group(P<0.05).The decrease was most significant in the 50μg/mL Feridex-labeled group(P<0.01).There were no significant differences in celluar viability and proliferation of BMSCs between the Feridex-labeled and non-labeled groups after 1 week(P>0.05). Low-signal lesions were detected in the rat hippocampus and temporal cortex at 3 days after transplantation.The low-signal lesions were still detectable at 14 days,and positively stained cells were observed in the hippocampus and temporal cortex using Prussian blue staining.There were no significant differences in signal intensity in the non-labeled group. CONCLUSION:BMSC transplantation traversed the blood-brain barrier and distributed into vulnerable zones in a rat model of cardiac arrest-induced global brain ischemia.MRI provided a non-invasive method to in vivo dynamically and spatially trace Feridex-labeled BMSCs after transplantation.
文摘The present study established a rat model of focal brain ischemia by occlusion of the middle cerebral artery covered with FeCl3, and investigated the protective effect of 3'-methoxy-puerarin. Hippocampal and cortical c-fos gene expression was determined using in situ hybridization. Results showed that 3'-methoxy-puerarin reduced neurological deficit scores, cerebral infarcted zone and water content of brain tissues, dramatically increased the activity of catalase and glutathione peroxidase in the ischemia zone of the hippocampus, increased the activity of catalase in the cortex, decreased lipid peroxide and lactic acid contents in the hippocampus and cerebral cortex, and down-regulated c-fos gene expression in brain ischemic rats. Results demonstrated that 3'-methoxy-puerarin exhibited cerebroprotective effects against focal brain ischemia, which involved c-fos gene expression.
基金supported by the National High Technology Research and Development Program of China(863 Program),No.2012AA020905the Biological Industry Development Funds of Shenzhen,No.JC201005260093A+1 种基金the National Natural Science Foundation of China/Research Grants Council Joint Research Scheme,No.81161160570the National Natural Science Foundation of China,No.81171143the Tsinghua-Yue-Yuen Medical Sciences Fund
文摘Transient brain ischemia has been shown to induce hyperphosphorylation of the microtubule-associated protein tau.To further determine the mechanisms underlying these processes,we investigated the interaction between tau,glycogen synthase kinase(GSK)-3βand protein phosphatase 2A.The results confirmed that tau protein was dephosphorylated during brain ischemia;in addition,the activity of GSK-3βwas increased and the activity of protein phosphatase2A was decreased.After reperfusion,tau protein was hyperphosphorylated,the activity of GSK-3βwas decreased and the activity of protein phosphatase 2A remained low.Importantly,the interaction of tau with GSK-3βand protein phosphatase 2A was altered during ischemia and reperfusion Lithium chloride could affect tau phosphorylation by regulating the interaction of tau with GSK-3βand protein phosphatase 2A,and improve learning and memory ability of rats after transient brain ischemia.The present study demonstrated that it was the interaction of tau with GSK-3βand protein phosphatase 2A,rather than their individual activities,that dominates the phosphorylation of tau in transient brain ischemia.Hyperphosphorylated tau protein may play an important role in the evolution of brain injury in ischemic stroke.The neuroprotective effects of lithium chloride partly depend on the inhibition of tau phosphorylation during transient brain ischemia.
基金the National Natural Science Foundation of China, No. 81000498the Natural Science Foundation of Nanjing Medical University, No. 09MJMUM107
文摘The traditional Chinese herb Astragalus membranaceus is a well-known treatment for neurological diseases and is considered to exhibit anti-dementia properties.This study investigated the synergistic effects of magnesium ions and Astragalus membranaceus on global brain ischemia in rats.4'-6-diamidino-2-phenylindole staining demonstrated that the number of living neurons was significantly greater in the rat hippocampus after administration of a combination of Astragalus membranaceus and magnesium,compared with a vehicle group,an Astragalus membranaceus alone group,and a magnesium alone group.Western blot assay revealed that cleaved Caspase-3 protein expression was significantly reduced in the rat hippocampus in the combined Astragalus membranaceus and magnesium group compared with the Astragalus membranaceus alone group and the magnesium alone group.The results suggested that the combination of Astragalus membranaceus and magnesium exhibits a stronger neuroprotective effect on global brain ischemia in rats compared with Astragalus membranaceus or magnesium alone.This effect was associated with decreased Caspase-3 expression.
文摘Ischemic stroke and irreversible consequences:Ischemic stroke in humans is the second most common cause of death in the world(Mozaffarian et al.,2016).The outcomes after a stroke are often dependent on complications,including motor disorders,depression and dementia(Pluta et al.,2018a),which causes a high risk of re-hospitalization and/or palliative care.This is also the main reason for long-term disability in people after stroke,with up to half of those who survived the stroke will not regain their independence until the end of their lives(Mozaffarian et al.,2016).According to epidemiological forecasts,human ischemic stroke will soon become the dominant cause of death worldwide(Bejot et al.,2016)as well as dementia with the phenotype of Alzheimer’s disease(AD;Kim and Lee 2018).It is suggested that human ischemic stroke and experimental brain ischemia in animals are associated with the possible development of AD neuropathology(Pluta et al.,2018a).
基金supported by the Science and Technology Development Foundation of Jilin Province,No.200905172
文摘A rat model of diabetes mellitus was induced by a high fat diet,followed by focal brain ischemia induced using the thread method after 0.5 month.Immunohistochemistry showed that expression of receptor for advanced glycation end-products was higher in the ischemic cortex of diabetic rats compared with non-diabetic rats with brain ischemia.Western blot assay revealed increased phosphorylated c-Jun N-terminal kinase expression,and unchanged phosphorylated extracellular signal-regulated protein kinase protein expression in the ischemic cortex of diabetic rats compared with non-diabetic rats with brain ischemia.Additionally,phosphorylated p38 mitogen-activated protein kinase protein was not detected in any rats in the two groups.Severity of limb hemiplegia was worse in diabetic rats with brain ischemia compared with ischemia alone rats.The results suggest that increased expression of receptor for advanced glycation end-products can further activate the c-Jun N-terminal kinase pathway in mitogen-activated protein kinase,thereby worsening brain injury associated with focal brain ischemia in diabetic rats.
文摘An update of the etiology of Alzheimer's disease(AD):The current theory of the etiology of AD and the guidelines for most of the wide-ranging treatments activities are built around amyloid and tau protein as causative agents of the disease(Atlante et al.,2020).At present,based on a comprehensive evaluation of existing and contemporary studies,important questions arise regarding the causal role of amyloid and tau protein in the pathogenesis of AD(Morris et al.,2018).Analyzes of the available evidence does not allow obvious conclusion that amyloid,and especially tau protein,plays a key role in the etiology of AD(Morris et al.,2018).
文摘We have previously reported that sequential common artery sectioning (SCAS) in mice produces a reproducible pattern of mortality, extensive brain damage and a wide range of measurable neurobehavioral alterations that include motor incoordination and forelimb flexion. The present study describes a comprehensive method to assess motor functional outcome after brain ischemia produced by SCAS using swimming behavior. We found that after the second artery occlusion the time for completion of the swimming task significantly increased and the swimming pattern alterations observed in the ischemic mice showed no evidence of recovery (up to 96 h). We view the swimming performance strategy described here as a sensitive, simple and economic procedure to assess motor performance after brain ischemia.
文摘Despite obvious progress in the treatment of acute forms of ischemic stroke, the risk of this condition remains unacceptably high. Brain infarction in the middle cerebral artery basin occurs in patients with atherosclerosis. The onset of the brain infarction is facilitated by the cessation of circulation (embolism) in conditions of insufficient collateral circulation. The extent of the infarct zone is determined by neuronal death and impaired microcirculation. The development of new methods for effective targeted restorative stroke therapy is crucial for restorative treatment and reducing the risk of mortality after stroke. Remote ischemic conditioning (RIC) is an approach to limiting reperfusion injury in the ischemic region of the brain after focal ischemia. One of the most commonly used <i>in vivo</i> models in stroke studies is the filament model of Middle Cerebral Artery Occlusion (MCAO) in rats. In our experiment, it was performed for 30 min (J. Koizumi) with subsequent 48-hour reperfusion. Within the first 24 hours after the start of reperfusion several short episodes of ischemia in low limbs were induced. After 48 hours of reperfusion the brains were harvested and stained with TTC. Then we evaluated the effect of RIC within 24 hours <i>ex vivo</i> in rats’ brains, as well as syndecan-1 plasma concentration. Infarct area was assessed by means of Image-Pro program with statistical analysis. Infarct volumes in the model group (31.97% ± 2.5%) were significantly higher compared to the values in the RIC group 48 hours after ischemia-reperfusion (13.6% ± 1.3%) (*P < 0.05). A significant reduction in the area of infarction after RIC is likely due to the effect on the regulation of collateral blood flow in the ischemia area. On the second day after ischemia-reperfusion, tissue swelling was reduced in the RIC group compared to the model group. Analysis of the average concentration of Syndecan-1 revealed the difference between model and RIC groups. Syndecan-1, endothelial glycocalyx protein, might be the regulator which performs vascular control of the interaction with inflammatory cell and is responsible for mediate effect of remote ischemic conditioning on the restriction of ischemic-reperfusion injury.
文摘Objective： To observe effects of Panax Notoginseng Saponin （PSN） on the expression of Vascular Endothelial Growth Factor （VEGF） after the brain ischemia-reperfusion injury in rats. Methods： 48 SD rats had been randomly divided into 4 groups： the sham operation group, the model group, Panax Notoginseng Saponin （PNS） group and Nimodipine group （n=12） . The rats had been treated with PNS, and 7 days later the rat focal cerebral ischemia-reperfusion models had been pre- pared. Neurobehavioral scores （NBS） had been evaluated in each group, TTC staining observed; the immunohistochemistry was used to observe VEGF and mRNA expressions. Results： PNS could not only improve significantly neurobehavioral scores and decrease dramatically cerebral infarct volume, but also increase remarkably VEGF and mRNA expression levels. Conclusion： The PNS is beneficial for rehabilitation after cerebral ischemia reperfusion injury via effectively up-regulating the injured cor- tical VEGF mRNA expression concentrations, which promotes vascular reborn in the ischemic region.
基金Supported by National Natural Science Foundation of China, No.3957263 and Natural Science Foundation of Guangdong province,No.
文摘Objective: To investigate the relationship between p53, p21 proteins and delayed neuronal death (DND) after reperfusion following forebrain ischemia in rats. Methods With four-vessel occlusion model of rats, the expression of p53, p21 proteins in brain tissue using labeled streptavindin-biotin immunohistochemical (LAAB) suming were observed. Re sults: The expression of p53, p21 proteins in brain was upregulated after reperfusion following 15 min forebrain ischemia and their distribution was similar. p53 and p21 proteins in brian sections was detected earlier in the white matter of hippocampal formation, thalamus, hypothalamus (6 h following reperfusion) than in the neuronal nuclei in cerebral cortex and CA1 region (24h), and the maximal induction was observed at 72 h following reperfusion. CA1 region suffered the most serious injury, where the positive expression of p53 and off proteins was most. Conclusion: Reperfusion following forebrain ischemia could upregulate the expression of p53 and p21 proteins in the brain region, suggesting that p53 and p21 proteins participate in and possibly promote the apoptosis of ’DND.
基金supported by the National Basic Research Program of China (973 Program),No.2003CB517104the National Natural Science Foundation of China,No.30973513+3 种基金Beijing Municipal Science and Technology Program,No.D0206001043191the Natural Science Foundation of Beijing,No.7112061Beijing Key Foundation of Traditional Chinese Medicine,No.KJTS2011-04Beijing Health and Technical Personal of High-Level Plan,No.2009-3-66
文摘In the present study, we hypothesized that 5-hydroxymethyl-2-furfural could attenuate ischemic brain damage by reducing oxidative injury. Thus, mice were subjected to bilateral common carotid artery occlusion to establish a model of permanent forebrain ischemia. The mice were intraperitoneally injected with 5-hydroxymethyl-2-furfural 30 minutes before ischemia or 5 minutes after ischemia. The survival time of mice injected with 5-hydroxymethyl-2-furfural was longer compared with untreated mice. The mice subjected to ischemia for 30 minutes and reperfusion for 5 minutes were intraperitoneally injected with 5-hydroxymethyl-2-furfural 5 minutes prior to reperfusion, which increased superoxide dismutase content and reduced malondialdehyde content, similar to the effects of Edaravone, a hydroxyl radical scavenger used for the treatment of stroke. These findings indicate that intraperitoneal injection of 5-hydroxymethyl-2-furfural can prolong the survival of mice with permanent forebrain ischemia. This outcome may be mediated by its antioxidative effects.
基金supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education,No.NRF-2013R1A1A2059364,NRF-2015R1D1A3A01020635)by 2013 Research Grant from Kangwon National Universitypartially supported by the Research Institute for Veterinary Science,Seoul National University
文摘Recent evidence exists that glucose transporter 3(GLUT3) plays an important role in the energy metabolism in the brain.Most previous studies have been conducted using focal or hypoxic ischemia models and have focused on changes in GLUT3 expression based on protein and m RNA levels rather than tissue levels.In the present study,we observed change in GLUT3 immunoreactivity in the adult gerbil hippocampus at various time points after 5 minutes of transient forebrain ischemia.In the sham-operated group,GLUT3 immunoreactivity in the hippocampal CA1 region was weak,in the pyramidal cells of the CA1 region increased in a time-dependent fashion 24 hours after ischemia,and in the hippocampal CA1 region decreased significantly between 2 and 5 days after ischemia,with high level of GLUT3 immunoreactivity observed in the CA1 region 10 days after ischemia.In a double immunofluorescence study using GLUT3 and glial-fibrillary acidic protein(GFAP),we observed strong GLUT3 immunoreactivity in the astrocytes.GLUT3 immunoreactivity increased after ischemia and peaked 7 days in the dentate gyrus after ischemia/reperfusion.In a double immunofluorescence study using GLUT3 and doublecortin(DCX),we observed low level of GLUT3 immunoreactivity in the differentiated neuroblasts of the subgranular zone of the dentate gyrus after ischemia.GLUT3 immunoreactivity in the sham-operated group was mainly detected in the subgranular zone of the dentate gyrus.These results suggest that the increase in GLUT3 immunoreactivity may be a compensatory mechanism to modulate glucose level in the hippocampal CA1 region and to promote adult neurogenesis in the dentate gyrus.
文摘Objective\ Exploring the alteration of glucocorticoid receptor (GCR) following forebrain ischemia in gerbils. Methods\ Establish a brain ischemia model by occluding bilateral common carotid. The GCR concentrations in forebrain tissue cytosol were detected by radioligand binding assay. The plasma concentrations of cortisol were determined by the method of competitive protein binding analysis. Results\ GCR concentrations had no significant change after 10 min ischemia (P>0 05), while decreased significantly in 1 h ischemia (P<0.01), and reduced more severely in 1 h ischemia followed by 3 h reperfusion (P<0.01). Plasma cortisol increased markedly in 10 min ischemia and 1 h ischemia (P<0.001), while decreased in 1 h ischemia followed by 3 h reperfusion. Conclusion\ GCR concentrations in brain decreased following forebrain ischemia in gerbil.
文摘BACKGROUND:Pharmacological studies have demonstrated that compound preparation Tongqiao Jiannao capsules composed of Zexie, Baizhu, Honghua, Danshen, and Shexiang can supplement qi, activate blood circulation, relieve blood stasis, induce resuscitation for alleviating pain, relieve pain, and dilate blood vessels. OBJECTIVE: To observe the effects of Tongqiao Jiannao capsules on the levels of the anti-apoptotic protein Bcl-2 and the proapoptotic protein Bax, and verify the mechanism of action. DESIGN, TIME AND SETTING: Randomized, controlled animal experiment, performed in the Laboratory of Biochemistry and Molecular Biology, Shanxi Medical University between June 2001 and December 2002. MATERIALS: The right middle cerebral arteries of 24 healthy adult Sprague Dawley rats were occluded by the suture method. The primary Chinese herbal medicinal ingredients of Tongqiao Jiannao capsules are Zexie, Baizhu, Honghua, Danshen, and Shexiang, which were purchased from Shanxi Provincial Medicinal Material Company, China, and prepared into condensed granules in the Room for Chinese Herbal Medicine Preparation, Second Hospital, Shanxi Medical University. Bcl-2 and Bax immunohistochemical staining kits, a 3,3-diaminobenzidine(DAB) kit, and an in situ apoptosis detection kit were purchased from Wuhan Boster Bioengineering Co., Ltd., China. METHODS: Twenty-four rats were randomly and evenly divided into three groups: (1) sham-operated rats in which sutures were inserted and immediately pulled out; (2) Tongqiao Jiannao capsule-treated rats that were intragastrically administered 6.5 g/kg/d Tongqiao Jiannao capsule preparation for seven successive days prior to middle cerebral artery occlusion (MCAO); and (3) MCAO rats without any other treatments. MAIN OUTCOME MEASURES: The levels of neural cell apoptosis and Bcl-2 and Bax proteins at 24 hours post-surgery. RESULTS: In the MCAO group, the numbers of apoptotic cells and Bax-positive cells were significantly increased, while the numbers of Bcl-2-positive cells were slightly decreased compared with the sham-operated group. Bcl-2- and Bax-positive cells and apoptotic cells were primarily distributed in the ischemic penumbra. In the Tongqiao Jiannao capsule-treated group, neuronal apoptosis was inhibited, and the number of Bcl-2-positive cells was significantly increased (P < 0.01), while the number of Bax-positive cells was significantly decreased (P < 0.01), compared with the MCAO group. CONCLUSION: Tongqiao Jiannao capsules elevated Bcl-2 expression, lowered Bax expression, and inhibited cellular apoptosis during the process of cerebral ischemia/reperfusion injury.
基金supported by the Scientific Research Fund of the National Natural Science Foundation of China ( 81201668 )Chengdu Science and Technology Bureau ( 2015HM01-00506-SF , 2018-YF05-00454-SN )+1 种基金Scientific Research Fund of the Sichuan Provincial Education Department (17CZ0011, 17ZA0109)the Scientific Research Fund of Chengdu Medical College (CYCG15-01)
文摘Honokiol(HK)usage is greatly restricted by its poor aqueous solubility and limited oral bioavailability.We synthesized and characterized a novel phosphate prodrug of honokiol(HKP)for in vitro and in vivo use.HKP greatly enhanced the aqueous solubility of HK(127.54±15.53 mg/ml)and the stability in buffer solution was sufficient for intravenous administration.The enzymatic hydrolysis of HKP to HK was extremely rapid in vitro(T 1/2=8.9±2.11 s).Pharmacokinetics studies demonstrated that after intravenous administration of HKP(32 mg/kg),HKP was converted rapidly to HK with a time to reach the maximum plasma concentration of^5 min.The prodrug HKP achieved an improved T 1/2(7.97±1.30 h)and terminal volume of distribution(26.02±6.04 ml/kg)compared with direct injection of the equimolar parent drug(0.66±0.01 h)and(2.90±0.342 ml/kg),respectively.Furthermore,oral administration of HKP showed rapid and improved absorption compared with the parent drug.HKP was confirmed to maintain the bioactivity of the parent drug for ameliorating ischemia-reperfusion injury by decreasing brain infarction and improving neurologic function.Taken together,HKP is a potentially useful aqueous-soluble prodrug with improved pharmacokinetic properties which may merit further development as a potential drug candidate.
