Objectives:We investigated whether the selective cerebral perfusion(SCP)technique causes differences in changes in cerebral perfusion between both hemispheres in young infants,using cerebral oxygen saturation(ScO2)as ...Objectives:We investigated whether the selective cerebral perfusion(SCP)technique causes differences in changes in cerebral perfusion between both hemispheres in young infants,using cerebral oxygen saturation(ScO2)as an index.Further,we determined the association between the discrepancy in ScO2 and cerebral perfu-sion pressure during SCP.Methods:The difference in ScO2 between the left and right cerebral hemispheres(ΔScO2 Rt-Lt)was calculated during clamping of the innominate artery(IA)and during SCP.Results:In 25 infants(aged 2 to 78 days),the left and right ScO2 were well maintained(median 63.2%and 60.9%during IA clamping,respectively;64.0%and 65.6%during SCP,respectively).During IA clamping,right and left ScO2 decreased(med-ian-1.4%and-1.0%,respectively).During SCP,rightΔScO2 was higher compared to leftΔScO2(median 1.5%vs.0.6%;p<0.001).Eight patients had a higher rightΔScO2 than leftΔScO2 throughout SCP.They had lowerΔScO2 Rt-Lt during IA clamping(median-3.2%vs.0.0%;p<0.001)and higherΔScO2 Rt-Lt during SCP than others(median 5.0%vs.-0.8%;p<0.001).During and after SCP,the correlation coefficient between rightΔScO2 and change in the mean arterial pressure was higher in patients with a discrepancy than in others(r=0.731 vs.r=0.519;p<0.001).Conclusions:This study suggests that SCP permits adequate bilateral cerebral perfusion.However,the unilateral cerebral perfusion technique may cause a difference in cerebral perfusion between both hemispheres in young infants;this may depend on the perfusion pressure.展开更多
BACKGROUND: Due to collateral circulation and cerebrovascular reserve, arterial stenosis and reduced cerebral blood flow may not necessarily indicate impaired cerebral perfusion. Therefore, according to degree of sten...BACKGROUND: Due to collateral circulation and cerebrovascular reserve, arterial stenosis and reduced cerebral blood flow may not necessarily indicate impaired cerebral perfusion. Therefore, according to degree of stenosis and clinical symptoms, interventional surgery to relieve arterial stenosis in transient ischemic attack (TIA) patients with major intracranial stenosis is imprudent. Rather, cerebral perfusion and reserve capacity are direct indicators for the assessment of degree and presence of cerebral ischemia. OBJECTIVE: To evaluate cerebral perfusion and reserve in TIA patients with major intracranial stenosis or occlusion using magnetic resonance-perfusion-weighted imaging (MR-PWI) data prior to and following diamox administration. DESIGN, TIME AND SETTING: A self-comparative, neuroimaging observation was performed at the Neurological Department and Radiological Center of the First Affiliated Hospital of Jinan University between December 2007 and April 2009. PARTICIPANTS: Seven acute TIA patients, who were admitted to the Neurological Department of the First Affiliated Hospital of Jinan University between December 2007 and April 2009, were enrolled in the present study. Magnetic resonance imaging confirmed that no acute cerebral infarction happened, nor did bleeding exist. Magnetic resonance angiography, transcranial Doppler ultrasound, and/or digital subtraction angiography confirmed the presence of major intracranial arterial stenosis. Clinical symptoms corresponded to blood supplying regions of the arterial stenosis. METHODS: Baseline MR-PWI was performed on seven patients with intracranial stenosis or occlusion. Two grams of acetazolamide (diamox) were orally administered after 2 days. A second PWI was performed after 2 hours to compare cerebral perfusion parameters prior to and following diamox administration. MAIN OUTCOME MEASURES: PWI results of cerebral perfusion prior to and following diamox administration. RESULTS: The baseline PWI from five patients indicated decreased cerebral perfusion areas. Following oral administration of diamox, cerebral perfusion significantly decreased in those areas. Moreover, new areas of decreased cerebral perfusion were observed in two out of the five patients. In one patient, no significant decrease in cerebral perfusion was found. In another patient, baseline PWI indicated decreased cerebral perfusion in the left hemisphere. However, normal perfusion was observed in both cerebral lobes following diamox administration. CONCLUSION: TIA patients with intracranial stenosis, who are diagnosed by PWI and exhibited decreased cerebral perfusion and reserve, might require further treatment such as intervention by angioplasty.展开更多
Cerebral perfusion computed tomography(PCT)is an important imaging modality for evaluating cerebrovascular diseases and stroke symptoms.With widespread public concern about the potential cancer risks and health hazard...Cerebral perfusion computed tomography(PCT)is an important imaging modality for evaluating cerebrovascular diseases and stroke symptoms.With widespread public concern about the potential cancer risks and health hazards associated with cumulative radiation exposure in PCT imaging,considerable research has been conducted to reduce the radiation dose in X-ray-based brain perfusion imaging.Reducing the dose of X-rays causes severe noise and artifacts in PCT images.To solve this problem,we propose a deep learning method called NCS-Unet.The exceptional characteristics of non-subsampled contourlet transform(NSCT)and the Sobel filter are introduced into NCS-Unet.NSCT decomposes the convolved features into high-and low-frequency components.The decomposed high-frequency component retains image edges,contrast imaging traces,and noise,whereas the low-frequency component retains the main image information.The Sobel filter extracts the contours of the original image and the imaging traces caused by the contrast agent decay.The extracted information is added to NCS-Unet to improve its performance in noise reduction and artifact removal.Qualitative and quantitative analyses demonstrated that the proposed NCS-Unet can improve the quality of low-dose cone-beam CT perfusion reconstruction images and the accuracy of perfusion parameter calculations.展开更多
Cerebrovascular disease is a disease with high morbidity,disability and mortality rates,which seri-ously affects the daily life of patients and is a heavy burden on families and society.Arterial spin labeling(ASL)is a...Cerebrovascular disease is a disease with high morbidity,disability and mortality rates,which seri-ously affects the daily life of patients and is a heavy burden on families and society.Arterial spin labeling(ASL)is a magnetic resonance imaging(MRI)technology that uses the magnetic labeling of hydrogen atoms in arterial blood as tracers to noninvasively evaluate brain blood flow.ASL does not require injection of an exogenous contrast agent,and has the advantages of no radiation,simplicity and low cost.In cerebrovascular diseases,ASL can evaluate the collateral cerebrovascular circulation and abnormal perfusion of brain tissue,which can provide a reliable basis for early diagnosis and clinical decision-making.This study reviewed ASL and its application in the diagnosis,treatment and prognosis of cerebrovascular diseases.展开更多
Objective To assess retrospectively the effects of different protective methods on brain in ascending aortic aneurysm surgery. Methods In 65 patients, aneurysm was dissected to the aortic arch or right arch. To protec...Objective To assess retrospectively the effects of different protective methods on brain in ascending aortic aneurysm surgery. Methods In 65 patients, aneurysm was dissected to the aortic arch or right arch. To protect brain, deep hypotermic circulatory arrest ( DHCA.) combined with retrograde cerebral perfusion ( RCP) June 2003 Vol11 No2 through the superior vena cava ( n = 50) and simple DHCA ( n = 15) were used during the procedure. Blood samples for lactic acid level from the jugular vein were compared in both groups at different plase, and perfusion blood distribution and oxygen content difference between the perfused and returned blood were measured in some RCP patients. Results The DHCA time was 35.9 ± 8 min (10. 0 - 63. 0 min) and DHCA+ RCP time was 45.5 ± 17. 2 min (16. 0 - 81. 0 min)The resuscitationtime was 7.1 ± 1.6 h (4.4 - 9.4H)in DHCA patients and 5.4±2.2h(2.0-9.0 h)in RCP patients. Operation death was 3/15 in the DHCA group and 1/50 in the RCP patients. Central nervous complication展开更多
BACKGROUND: It is crucial to understand cerebral perfusion and vascular reserve in stegnotic arterial blood-supply regions to treat ischemic cerebrovascular diseases. However, effects on symptomatic intracra- nial art...BACKGROUND: It is crucial to understand cerebral perfusion and vascular reserve in stegnotic arterial blood-supply regions to treat ischemic cerebrovascular diseases. However, effects on symptomatic intracra- nial arterial stenosis (SICAS) need to be further studied in additional applications. OBJECTIVE: To evaluate and summarize the effects of cerebral perfusion and vascular reserve on the treatment of SICAS. RETRIEVAL STRATEGY: A computer-based online search of English language publications from January 2000 to July 2007 was conducted in PubMed to identify publications that addressed cerebral perfusion and vascular reserve of SICAS.展开更多
Global cerebral perfusion parameters were measured using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) in eight healthy volunteers examined during normal breathing and spontaneous hyperventilati...Global cerebral perfusion parameters were measured using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) in eight healthy volunteers examined during normal breathing and spontaneous hyperventilation. DSC-MRI-based cerebral blood flow (CBF) de-creased during hyperventilation in all volun-teers (average decrease 29%), and the corre-sponding global CBF estimates were 73±19ml/ (min100g) during normal breathing and 52± 7.9ml/(min100g) during hyperventilation (mean ±SD, n=8). Furthermore, the hypocapnic condi-tions induced by hyperventilation resulted in a prolongation of the global mean transit time (MTT) by on average 14%. The observed CBF estimates appeared to be systematically over-estimated, in accordance with previously pub-lished DSC-MRI results, but reduced to more reasonable levels when a previously retrieved calibration factor was applied.展开更多
To compare the protective effects to brain between continuous selective cerebral perfusion via right subclavian artery (RSA) and retrograde cerebral perfusion via superior vena cava (SVC) during deep hypothermic circu...To compare the protective effects to brain between continuous selective cerebral perfusion via right subclavian artery (RSA) and retrograde cerebral perfusion via superior vena cava (SVC) during deep hypothermic circulatory arrest (DHCA).Methods Thirty-six hybrid cats with both sexes were randomly divided into 6 groups (n=6 in each).Group 1:DHCA for 45 min with no cerebral perfusion; Group 2:DHCA for 45 min with retrograde perfusion via SVC;Group 3:DHCA for 45 min with perfusion via RSA;Group 4:DHCA for 90 min with no cerebral perfusion; Group 5:DHCA for 90 minwith retrograde perfusion via SVC;Group 6:DHCA for 90 min with perfusion via RSA.Ultrastructure of cerebral tissue,lactate content in venous return blood,ATP content in cerebral tissue and activity of nitric oxide synthetase (NOS) in cerebral cells were measured.Results At the same DHCA time,groups with RSA and SVC had milder hypoxia changes of brain ultrastructure than that of groups with no cerebral perfusion.The lactate content and activity of cerebral NOS in groups with RSA and SVC were significantly lower than those in the groups with no cerebral perfusion (P<0.05), and ATP content in cerebral tissue were significantly higher (P<0.05).There were no significant differences between SVC group and RSA group in all of the indexes after DHCA for 45 min.After DHCA for 90 min,the ATP content in cerebral tissue in RSA group (2.02±0.19) μmol/g was significantly higher than that in SVC group [(1.72±0.21) μmol/g,P<0.05].Conclusion For the profit of brain protection,perfusion via RSA is a better way than retrograde perfusion via SVC during long period of DHCA.2 refs,3 tabs.展开更多
Stroke is one of the leading causes of death and disability worldwide.However,information on stroke-related tongue coating microbiome(TCM)is limited,and whether TCM modulation could benefit for stroke prevention and r...Stroke is one of the leading causes of death and disability worldwide.However,information on stroke-related tongue coating microbiome(TCM)is limited,and whether TCM modulation could benefit for stroke prevention and rehabilitation is unknown.Here,TCM from stroke patients(SP)was characterized using molecular techniques.The occurrence of stroke resulted in TCM dysbiosis with significantly reduced species richness and diversity.The abundance of Prevotella,Leptotrichia,Actinomyces,Alloprevotella,Haemophilus,and TM7_[G-1]were greatly reduced,but common infection Streptococcus and Pseudomonas were remarkably increased.Furthermore,an antioxidative probiotic Lactiplantibacillus plantarum AR113 was used for TCM intervention in stroke rats with cerebral ischemia/reperfusion(I/R).AR113 partly restored I/R induced change of TCM and gut microbiota with significantly improved neurological deficit,relieved histopathologic change,increased activities of antioxidant enzymes,and decreased contents of oxidative stress biomarkers.Moreover,the gene expression of antioxidant-related proteins and apoptosis-related factors heme oxygenase-1(HO-1),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),nuclear factor erythroid 2-related factor 2(Nrf2),NAD(P)H:quinone oxidoreductase-1(NQO-1),and Bcl-2 was significantly increased,but cytochrome C,cleaved caspase-3,and Bax were markedly decreased in the brain by AR113 treatment.The results suggested that AR113 could ameliorate cerebral I/R injury through antioxidation and anti-apoptosis pathways,and AR113 intervention of TCM may have the application potential for stroke prevention and control.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
Studies have shown that C1q/tumor necrosis factor-related protein-6 (CTRP6) can alleviate renal ischemia/reperfusion injury in mice. However, its role in the brain remains poorly understood. To investigate the role of...Studies have shown that C1q/tumor necrosis factor-related protein-6 (CTRP6) can alleviate renal ischemia/reperfusion injury in mice. However, its role in the brain remains poorly understood. To investigate the role of CTRP6 in cerebral ischemia/reperfusion injury associated with diabetes mellitus, a diabetes mellitus mouse model of cerebral ischemia/reperfusion injury was established by occlusion of the middle cerebral artery. To overexpress CTRP6 in the brain, an adeno-associated virus carrying CTRP6 was injected into the lateral ventricle. The result was that oxygen injury and inflammation in brain tissue were clearly attenuated, and the number of neurons was greatly reduced. In vitro experiments showed that CTRP6 knockout exacerbated oxidative damage, inflammatory reaction, and apoptosis in cerebral cortical neurons in high glucose hypoxia-simulated diabetic cerebral ischemia/reperfusion injury. CTRP6 overexpression enhanced the sirtuin-1 signaling pathway in diabetic brains after ischemia/reperfusion injury. To investigate the mechanism underlying these effects, we examined mice with depletion of brain tissue-specific sirtuin-1. CTRP6-like protection was achieved by activating the sirtuin-1 signaling pathway. Taken together, these results indicate that CTRP6 likely attenuates cerebral ischemia/reperfusion injury through activation of the sirtuin-1 signaling pathway.展开更多
β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unkno...β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic stroke.Here we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced apoptosis.Further investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke.In addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its activity.In conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.展开更多
Calcium influx into neurons triggers neuronal death during cerebral ischemia/reperfusion injury.Various calcium channels are involved in cerebral ischemia/reperfusion injury.Cav3.2 channel is a main subtype of T-type ...Calcium influx into neurons triggers neuronal death during cerebral ischemia/reperfusion injury.Various calcium channels are involved in cerebral ischemia/reperfusion injury.Cav3.2 channel is a main subtype of T-type calcium channels.T-type calcium channel blockers,such as pimozide and mibefradil,have been shown to prevent cerebral ischemia/reperfusion injury-induced brain injury.However,the role of Cav3.2 channels in cerebral ischemia/reperfusion injury remains unclear.Here,in vitro and in vivo models of cerebral ischemia/reperfusion injury were established using middle cerebral artery occlusion in mice and high glucose hypoxia/reoxygenation exposure in primary hippocampal neurons.The results showed that Cav3.2 expression was significantly upregulated in injured hippocampal tissue and primary hippocampal neurons.We further established a Cav3.2 gene-knockout mouse model of cerebral ischemia/reperfusion injury.Cav3.2 knockout markedly reduced infarct volume and brain water content,and alleviated neurological dysfunction after cerebral ischemia/reperfusion injury.Additionally,Cav3.2 knockout attenuated cerebral ischemia/reperfusion injury-induced oxidative stress,inflammatory response,and neuronal apoptosis.In the hippocampus of Cav3.2-knockout mice,calcineurin overexpression offset the beneficial effect of Cav3.2 knockout after cerebral ischemia/reperfusion injury.These findings suggest that the neuroprotective function of Cav3.2 knockout is mediated by calcineurin/nuclear factor of activated T cells 3 signaling.Findings from this study suggest that Cav3.2 could be a promising target for treatment of cerebral ischemia/reperfusion injury.展开更多
Microglia,which are the resident macrophages of the central nervous system,are an important part of the inflammatory response that occurs after cerebral ischemia.Vav guanine nucleotide exchange factor 1(Vav1) is a gua...Microglia,which are the resident macrophages of the central nervous system,are an important part of the inflammatory response that occurs after cerebral ischemia.Vav guanine nucleotide exchange factor 1(Vav1) is a guanine nucleotide exchange factor that is related to microglial activation.However,how Vav1 participates in the inflammato ry response after cerebral ischemia/reperfusion inj ury remains unclea r.In this study,we subjected rats to occlusion and repe rfusion of the middle cerebral artery and subjected the BV-2 mic roglia cell line to oxygen-glucose deprivatio n/reoxygenation to mimic cerebral ischemia/repe rfusion in vivo and in vitro,respectively.We found that Vav1 levels were increased in the brain tissue of rats subjected to occlusion and reperfusion of the middle cerebral arte ry and in BV-2 cells subjected to oxygen-glucose deprivation/reoxygenation.Silencing Vav1 reduced the cerebral infarct volume and brain water content,inhibited neuronal loss and apoptosis in the ischemic penumbra,and im p roved neurological function in rats subjected to occlusion and repe rfusion of the middle cerebral artery.Further analysis showed that Vav1 was almost exclusively localized to microglia and that Vav1 downregulation inhibited microglial activation and the NOD-like receptor pyrin 3(NLRP3) inflammasome in the ischemic penumbra,as well as the expression of inflammato ry facto rs.In addition,Vov1 knoc kdown decreased the inflammatory response exhibited by BV-2 cells after oxygen-glucose deprivation/reoxyge nation.Taken together,these findings show that silencing Vav1 attenuates inflammation and neuronal apoptosis in rats subjected to cerebral ischemia/repe rfusion through inhibiting the activation of mic roglia and NLRP3 inflammasome.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
Objective To evaluate the utility of computed tomography perfusion(CTP)both at admission and during delayed cerebral ischemia time-window(DCITW)in the detection of delayed cerebral ischemia(DCI)and the change in CTP p...Objective To evaluate the utility of computed tomography perfusion(CTP)both at admission and during delayed cerebral ischemia time-window(DCITW)in the detection of delayed cerebral ischemia(DCI)and the change in CTP parameters from admission to DCITW following aneurysmal subarachnoid hemorrhage.Methods Eighty patients underwent CTP at admission and during DCITW.The mean and extreme values of all CTP parameters at admission and during DCITW were compared between the DCI group and non-DCI group,and comparisons were also made between admission and DCITW within each group.The qualitative color-coded perfusion maps were recorded.Finally,the relationship between CTP parameters and DCI was assessed by receiver operating characteristic(ROC)analyses.Results With the exception of cerebral blood volume(P=0.295,admission;P=0.682,DCITW),there were significant differences in the mean quantitative CTP parameters between DCI and non-DCI patients both at admission and during DCITW.In the DCI group,the extreme parameters were significantly different between admission and DCITW.The DCI group also showed a deteriorative trend in the qualitative color-coded perfusion maps.For the detection of DCI,mean transit time to the center of the impulse response function(Tmax)at admission and mean time to start(TTS)during DCITW had the largest area under curve(AUC),0.698 and 0.789,respectively.Conclusion Whole-brain CTP can predict the occurrence of DCI at admission and diagnose DCI during DCITW.The extreme quantitative parameters and qualitative color-coded perfusion maps can better reflect the perfusion changes of patients with DCI from admission to DCITW.展开更多
In vivo imaging of cerebral ischemia/reperfusion injury remains an important challenge.We injected porous Ag/Au@SiO_(2) bimetallic hollow nanoshells carrying anti-tropomyosin 4 as a molecular probe into mice with cere...In vivo imaging of cerebral ischemia/reperfusion injury remains an important challenge.We injected porous Ag/Au@SiO_(2) bimetallic hollow nanoshells carrying anti-tropomyosin 4 as a molecular probe into mice with cerebral ischemia/reperfusion injury and observed microvascular changes in the brain using photoacoustic imaging with ultrasonography.At each measured time point,the total photoacoustic signal was significantly higher on the affected side than on the healthy side.Twelve hours after reperfusion,cerebral perfusion on the affected side increased,cerebrovascular injury worsened,and anti-tropomyosin 4 expression increased.Twenty-four hours after reperfusion and later,perfusion on the affected side declined slowly and stabilized after 1 week;brain injury was also alleviated.Histopathological and immunohistochemical examinations confirmed the brain injury tissue changes.The nanoshell molecular probe carrying anti-tropomyosin 4 has potential for use in early diagnosis of cerebral ischemia/reperfusion injury and evaluating its progression.展开更多
Ischemic cerebrovascular disease is a leading cause of death globally and is often exacerbated by cerebral ischemic/reperfusion injury(CIRI).The exact mechanisms underlying I/R injury are unclear.In this study,we aime...Ischemic cerebrovascular disease is a leading cause of death globally and is often exacerbated by cerebral ischemic/reperfusion injury(CIRI).The exact mechanisms underlying I/R injury are unclear.In this study,we aimed to determine the role of m6A-modified methylase complex methyltransferase-like 3(METTL3)in cerebral ischemiareperfusion(I/R)injury.We found that m6A and METTL3 levels increased in OGD/RX-induced mouse astrocytescerebellar(MA-C)and the brain of middle cerebral artery occlusion(MCAO)model mice.METTL3 siRNA treatment reduced OGD-RX-induced MAC cell viability and proliferation,which increased with METTL3 over-expression.Flow cytometry analysis showed that silencing METTL3 significantly enhanced OGD/RX-induced MAC apoptosis,which was significantly reduced with METTL3 up-regulation.In an MCAO model,METTL3 overexpression significantly reduced cerebral infarction area and decreased brain cell apoptosis,indicating that METTL3 OE treatment could ameliorate brain edema and injury.Thus,METTL3 could be used as a target to treat I/R injury.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
基金supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute,funded by the Ministry of Health&Welfare of the Republic of Korea(HI18C2383).
文摘Objectives:We investigated whether the selective cerebral perfusion(SCP)technique causes differences in changes in cerebral perfusion between both hemispheres in young infants,using cerebral oxygen saturation(ScO2)as an index.Further,we determined the association between the discrepancy in ScO2 and cerebral perfu-sion pressure during SCP.Methods:The difference in ScO2 between the left and right cerebral hemispheres(ΔScO2 Rt-Lt)was calculated during clamping of the innominate artery(IA)and during SCP.Results:In 25 infants(aged 2 to 78 days),the left and right ScO2 were well maintained(median 63.2%and 60.9%during IA clamping,respectively;64.0%and 65.6%during SCP,respectively).During IA clamping,right and left ScO2 decreased(med-ian-1.4%and-1.0%,respectively).During SCP,rightΔScO2 was higher compared to leftΔScO2(median 1.5%vs.0.6%;p<0.001).Eight patients had a higher rightΔScO2 than leftΔScO2 throughout SCP.They had lowerΔScO2 Rt-Lt during IA clamping(median-3.2%vs.0.0%;p<0.001)and higherΔScO2 Rt-Lt during SCP than others(median 5.0%vs.-0.8%;p<0.001).During and after SCP,the correlation coefficient between rightΔScO2 and change in the mean arterial pressure was higher in patients with a discrepancy than in others(r=0.731 vs.r=0.519;p<0.001).Conclusions:This study suggests that SCP permits adequate bilateral cerebral perfusion.However,the unilateral cerebral perfusion technique may cause a difference in cerebral perfusion between both hemispheres in young infants;this may depend on the perfusion pressure.
基金Medical Scientific and Technological Research Foundation of Guangdong Province, No. 2007332 2009360the Natural Science Foundation of Guangdong Province, No. 9451063201002951
文摘BACKGROUND: Due to collateral circulation and cerebrovascular reserve, arterial stenosis and reduced cerebral blood flow may not necessarily indicate impaired cerebral perfusion. Therefore, according to degree of stenosis and clinical symptoms, interventional surgery to relieve arterial stenosis in transient ischemic attack (TIA) patients with major intracranial stenosis is imprudent. Rather, cerebral perfusion and reserve capacity are direct indicators for the assessment of degree and presence of cerebral ischemia. OBJECTIVE: To evaluate cerebral perfusion and reserve in TIA patients with major intracranial stenosis or occlusion using magnetic resonance-perfusion-weighted imaging (MR-PWI) data prior to and following diamox administration. DESIGN, TIME AND SETTING: A self-comparative, neuroimaging observation was performed at the Neurological Department and Radiological Center of the First Affiliated Hospital of Jinan University between December 2007 and April 2009. PARTICIPANTS: Seven acute TIA patients, who were admitted to the Neurological Department of the First Affiliated Hospital of Jinan University between December 2007 and April 2009, were enrolled in the present study. Magnetic resonance imaging confirmed that no acute cerebral infarction happened, nor did bleeding exist. Magnetic resonance angiography, transcranial Doppler ultrasound, and/or digital subtraction angiography confirmed the presence of major intracranial arterial stenosis. Clinical symptoms corresponded to blood supplying regions of the arterial stenosis. METHODS: Baseline MR-PWI was performed on seven patients with intracranial stenosis or occlusion. Two grams of acetazolamide (diamox) were orally administered after 2 days. A second PWI was performed after 2 hours to compare cerebral perfusion parameters prior to and following diamox administration. MAIN OUTCOME MEASURES: PWI results of cerebral perfusion prior to and following diamox administration. RESULTS: The baseline PWI from five patients indicated decreased cerebral perfusion areas. Following oral administration of diamox, cerebral perfusion significantly decreased in those areas. Moreover, new areas of decreased cerebral perfusion were observed in two out of the five patients. In one patient, no significant decrease in cerebral perfusion was found. In another patient, baseline PWI indicated decreased cerebral perfusion in the left hemisphere. However, normal perfusion was observed in both cerebral lobes following diamox administration. CONCLUSION: TIA patients with intracranial stenosis, who are diagnosed by PWI and exhibited decreased cerebral perfusion and reserve, might require further treatment such as intervention by angioplasty.
基金supported in part by Science and Technology Program of Guangdong (No. 2018B030333001)the State’s Key Project of Research and Development Plan (Nos. 2017YFC0109202,2017YFA0104302 and 2017YFC0107900)the National Natural Science Foundation (Nos. 81530060 and 61871117)
文摘Cerebral perfusion computed tomography(PCT)is an important imaging modality for evaluating cerebrovascular diseases and stroke symptoms.With widespread public concern about the potential cancer risks and health hazards associated with cumulative radiation exposure in PCT imaging,considerable research has been conducted to reduce the radiation dose in X-ray-based brain perfusion imaging.Reducing the dose of X-rays causes severe noise and artifacts in PCT images.To solve this problem,we propose a deep learning method called NCS-Unet.The exceptional characteristics of non-subsampled contourlet transform(NSCT)and the Sobel filter are introduced into NCS-Unet.NSCT decomposes the convolved features into high-and low-frequency components.The decomposed high-frequency component retains image edges,contrast imaging traces,and noise,whereas the low-frequency component retains the main image information.The Sobel filter extracts the contours of the original image and the imaging traces caused by the contrast agent decay.The extracted information is added to NCS-Unet to improve its performance in noise reduction and artifact removal.Qualitative and quantitative analyses demonstrated that the proposed NCS-Unet can improve the quality of low-dose cone-beam CT perfusion reconstruction images and the accuracy of perfusion parameter calculations.
文摘Cerebrovascular disease is a disease with high morbidity,disability and mortality rates,which seri-ously affects the daily life of patients and is a heavy burden on families and society.Arterial spin labeling(ASL)is a magnetic resonance imaging(MRI)technology that uses the magnetic labeling of hydrogen atoms in arterial blood as tracers to noninvasively evaluate brain blood flow.ASL does not require injection of an exogenous contrast agent,and has the advantages of no radiation,simplicity and low cost.In cerebrovascular diseases,ASL can evaluate the collateral cerebrovascular circulation and abnormal perfusion of brain tissue,which can provide a reliable basis for early diagnosis and clinical decision-making.This study reviewed ASL and its application in the diagnosis,treatment and prognosis of cerebrovascular diseases.
文摘Objective To assess retrospectively the effects of different protective methods on brain in ascending aortic aneurysm surgery. Methods In 65 patients, aneurysm was dissected to the aortic arch or right arch. To protect brain, deep hypotermic circulatory arrest ( DHCA.) combined with retrograde cerebral perfusion ( RCP) June 2003 Vol11 No2 through the superior vena cava ( n = 50) and simple DHCA ( n = 15) were used during the procedure. Blood samples for lactic acid level from the jugular vein were compared in both groups at different plase, and perfusion blood distribution and oxygen content difference between the perfused and returned blood were measured in some RCP patients. Results The DHCA time was 35.9 ± 8 min (10. 0 - 63. 0 min) and DHCA+ RCP time was 45.5 ± 17. 2 min (16. 0 - 81. 0 min)The resuscitationtime was 7.1 ± 1.6 h (4.4 - 9.4H)in DHCA patients and 5.4±2.2h(2.0-9.0 h)in RCP patients. Operation death was 3/15 in the DHCA group and 1/50 in the RCP patients. Central nervous complication
基金the Medical Science and Technique Foundation of Guangdong Province, No. A2007332
文摘BACKGROUND: It is crucial to understand cerebral perfusion and vascular reserve in stegnotic arterial blood-supply regions to treat ischemic cerebrovascular diseases. However, effects on symptomatic intracra- nial arterial stenosis (SICAS) need to be further studied in additional applications. OBJECTIVE: To evaluate and summarize the effects of cerebral perfusion and vascular reserve on the treatment of SICAS. RETRIEVAL STRATEGY: A computer-based online search of English language publications from January 2000 to July 2007 was conducted in PubMed to identify publications that addressed cerebral perfusion and vascular reserve of SICAS.
文摘Global cerebral perfusion parameters were measured using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) in eight healthy volunteers examined during normal breathing and spontaneous hyperventilation. DSC-MRI-based cerebral blood flow (CBF) de-creased during hyperventilation in all volun-teers (average decrease 29%), and the corre-sponding global CBF estimates were 73±19ml/ (min100g) during normal breathing and 52± 7.9ml/(min100g) during hyperventilation (mean ±SD, n=8). Furthermore, the hypocapnic condi-tions induced by hyperventilation resulted in a prolongation of the global mean transit time (MTT) by on average 14%. The observed CBF estimates appeared to be systematically over-estimated, in accordance with previously pub-lished DSC-MRI results, but reduced to more reasonable levels when a previously retrieved calibration factor was applied.
文摘To compare the protective effects to brain between continuous selective cerebral perfusion via right subclavian artery (RSA) and retrograde cerebral perfusion via superior vena cava (SVC) during deep hypothermic circulatory arrest (DHCA).Methods Thirty-six hybrid cats with both sexes were randomly divided into 6 groups (n=6 in each).Group 1:DHCA for 45 min with no cerebral perfusion; Group 2:DHCA for 45 min with retrograde perfusion via SVC;Group 3:DHCA for 45 min with perfusion via RSA;Group 4:DHCA for 90 min with no cerebral perfusion; Group 5:DHCA for 90 minwith retrograde perfusion via SVC;Group 6:DHCA for 90 min with perfusion via RSA.Ultrastructure of cerebral tissue,lactate content in venous return blood,ATP content in cerebral tissue and activity of nitric oxide synthetase (NOS) in cerebral cells were measured.Results At the same DHCA time,groups with RSA and SVC had milder hypoxia changes of brain ultrastructure than that of groups with no cerebral perfusion.The lactate content and activity of cerebral NOS in groups with RSA and SVC were significantly lower than those in the groups with no cerebral perfusion (P<0.05), and ATP content in cerebral tissue were significantly higher (P<0.05).There were no significant differences between SVC group and RSA group in all of the indexes after DHCA for 45 min.After DHCA for 90 min,the ATP content in cerebral tissue in RSA group (2.02±0.19) μmol/g was significantly higher than that in SVC group [(1.72±0.21) μmol/g,P<0.05].Conclusion For the profit of brain protection,perfusion via RSA is a better way than retrograde perfusion via SVC during long period of DHCA.2 refs,3 tabs.
基金supported by National Science Fund for Distinguished Young Scholars(grant No.32025029)Shanghai Education Committee Scientific Research Innovation Project(grant No.2101070007800120)+1 种基金Clinical research project in health industry of Shanghai Municipal Health Commission(202240379)the Development Fund for Shanghai Talents(grant No.2021077).
文摘Stroke is one of the leading causes of death and disability worldwide.However,information on stroke-related tongue coating microbiome(TCM)is limited,and whether TCM modulation could benefit for stroke prevention and rehabilitation is unknown.Here,TCM from stroke patients(SP)was characterized using molecular techniques.The occurrence of stroke resulted in TCM dysbiosis with significantly reduced species richness and diversity.The abundance of Prevotella,Leptotrichia,Actinomyces,Alloprevotella,Haemophilus,and TM7_[G-1]were greatly reduced,but common infection Streptococcus and Pseudomonas were remarkably increased.Furthermore,an antioxidative probiotic Lactiplantibacillus plantarum AR113 was used for TCM intervention in stroke rats with cerebral ischemia/reperfusion(I/R).AR113 partly restored I/R induced change of TCM and gut microbiota with significantly improved neurological deficit,relieved histopathologic change,increased activities of antioxidant enzymes,and decreased contents of oxidative stress biomarkers.Moreover,the gene expression of antioxidant-related proteins and apoptosis-related factors heme oxygenase-1(HO-1),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),nuclear factor erythroid 2-related factor 2(Nrf2),NAD(P)H:quinone oxidoreductase-1(NQO-1),and Bcl-2 was significantly increased,but cytochrome C,cleaved caspase-3,and Bax were markedly decreased in the brain by AR113 treatment.The results suggested that AR113 could ameliorate cerebral I/R injury through antioxidation and anti-apoptosis pathways,and AR113 intervention of TCM may have the application potential for stroke prevention and control.
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.
基金supported by the National Natural Science Foundation of China,Nos.82102295(to WG),82071339(to LG),82001119(to JH),and 81901994(to BZ).
文摘Studies have shown that C1q/tumor necrosis factor-related protein-6 (CTRP6) can alleviate renal ischemia/reperfusion injury in mice. However, its role in the brain remains poorly understood. To investigate the role of CTRP6 in cerebral ischemia/reperfusion injury associated with diabetes mellitus, a diabetes mellitus mouse model of cerebral ischemia/reperfusion injury was established by occlusion of the middle cerebral artery. To overexpress CTRP6 in the brain, an adeno-associated virus carrying CTRP6 was injected into the lateral ventricle. The result was that oxygen injury and inflammation in brain tissue were clearly attenuated, and the number of neurons was greatly reduced. In vitro experiments showed that CTRP6 knockout exacerbated oxidative damage, inflammatory reaction, and apoptosis in cerebral cortical neurons in high glucose hypoxia-simulated diabetic cerebral ischemia/reperfusion injury. CTRP6 overexpression enhanced the sirtuin-1 signaling pathway in diabetic brains after ischemia/reperfusion injury. To investigate the mechanism underlying these effects, we examined mice with depletion of brain tissue-specific sirtuin-1. CTRP6-like protection was achieved by activating the sirtuin-1 signaling pathway. Taken together, these results indicate that CTRP6 likely attenuates cerebral ischemia/reperfusion injury through activation of the sirtuin-1 signaling pathway.
基金supported by the National Natural Science Foundation of China,Nos.82104158(to XT),31800887(to LY),31972902(to LY),82001422(to YL)China Postdoctoral Science Foundation,No.2020M683750(to LY)partially by Young Talent Fund of University Association for Science and Technology in Shaanxi Province of China,No.20200307(to LY).
文摘β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic stroke.Here we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced apoptosis.Further investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke.In addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its activity.In conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.
基金supported by the Natural Science Foundation of Anhui Province of China,No.2208085Y32Scientific Research Plan Project of Anhui Province of China,No.2022AH020076the Chen Xiao-Ping Foundation for the Development of Science and Technology of Hubei Province,No.CXPJJH12000005-07-115(all to CT).
文摘Calcium influx into neurons triggers neuronal death during cerebral ischemia/reperfusion injury.Various calcium channels are involved in cerebral ischemia/reperfusion injury.Cav3.2 channel is a main subtype of T-type calcium channels.T-type calcium channel blockers,such as pimozide and mibefradil,have been shown to prevent cerebral ischemia/reperfusion injury-induced brain injury.However,the role of Cav3.2 channels in cerebral ischemia/reperfusion injury remains unclear.Here,in vitro and in vivo models of cerebral ischemia/reperfusion injury were established using middle cerebral artery occlusion in mice and high glucose hypoxia/reoxygenation exposure in primary hippocampal neurons.The results showed that Cav3.2 expression was significantly upregulated in injured hippocampal tissue and primary hippocampal neurons.We further established a Cav3.2 gene-knockout mouse model of cerebral ischemia/reperfusion injury.Cav3.2 knockout markedly reduced infarct volume and brain water content,and alleviated neurological dysfunction after cerebral ischemia/reperfusion injury.Additionally,Cav3.2 knockout attenuated cerebral ischemia/reperfusion injury-induced oxidative stress,inflammatory response,and neuronal apoptosis.In the hippocampus of Cav3.2-knockout mice,calcineurin overexpression offset the beneficial effect of Cav3.2 knockout after cerebral ischemia/reperfusion injury.These findings suggest that the neuroprotective function of Cav3.2 knockout is mediated by calcineurin/nuclear factor of activated T cells 3 signaling.Findings from this study suggest that Cav3.2 could be a promising target for treatment of cerebral ischemia/reperfusion injury.
基金Natural Science Foundation of Liaoning Province (General Program),No.2017010825 (to JQ)。
文摘Microglia,which are the resident macrophages of the central nervous system,are an important part of the inflammatory response that occurs after cerebral ischemia.Vav guanine nucleotide exchange factor 1(Vav1) is a guanine nucleotide exchange factor that is related to microglial activation.However,how Vav1 participates in the inflammato ry response after cerebral ischemia/reperfusion inj ury remains unclea r.In this study,we subjected rats to occlusion and repe rfusion of the middle cerebral artery and subjected the BV-2 mic roglia cell line to oxygen-glucose deprivatio n/reoxygenation to mimic cerebral ischemia/repe rfusion in vivo and in vitro,respectively.We found that Vav1 levels were increased in the brain tissue of rats subjected to occlusion and reperfusion of the middle cerebral arte ry and in BV-2 cells subjected to oxygen-glucose deprivation/reoxygenation.Silencing Vav1 reduced the cerebral infarct volume and brain water content,inhibited neuronal loss and apoptosis in the ischemic penumbra,and im p roved neurological function in rats subjected to occlusion and repe rfusion of the middle cerebral artery.Further analysis showed that Vav1 was almost exclusively localized to microglia and that Vav1 downregulation inhibited microglial activation and the NOD-like receptor pyrin 3(NLRP3) inflammasome in the ischemic penumbra,as well as the expression of inflammato ry facto rs.In addition,Vov1 knoc kdown decreased the inflammatory response exhibited by BV-2 cells after oxygen-glucose deprivation/reoxyge nation.Taken together,these findings show that silencing Vav1 attenuates inflammation and neuronal apoptosis in rats subjected to cerebral ischemia/repe rfusion through inhibiting the activation of mic roglia and NLRP3 inflammasome.
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.
基金supported by the National Natural Science Foundation of China,Research on Brain Magnetic Resonance Image Segmentation Based on Particle Computation(No.61672386).
文摘Objective To evaluate the utility of computed tomography perfusion(CTP)both at admission and during delayed cerebral ischemia time-window(DCITW)in the detection of delayed cerebral ischemia(DCI)and the change in CTP parameters from admission to DCITW following aneurysmal subarachnoid hemorrhage.Methods Eighty patients underwent CTP at admission and during DCITW.The mean and extreme values of all CTP parameters at admission and during DCITW were compared between the DCI group and non-DCI group,and comparisons were also made between admission and DCITW within each group.The qualitative color-coded perfusion maps were recorded.Finally,the relationship between CTP parameters and DCI was assessed by receiver operating characteristic(ROC)analyses.Results With the exception of cerebral blood volume(P=0.295,admission;P=0.682,DCITW),there were significant differences in the mean quantitative CTP parameters between DCI and non-DCI patients both at admission and during DCITW.In the DCI group,the extreme parameters were significantly different between admission and DCITW.The DCI group also showed a deteriorative trend in the qualitative color-coded perfusion maps.For the detection of DCI,mean transit time to the center of the impulse response function(Tmax)at admission and mean time to start(TTS)during DCITW had the largest area under curve(AUC),0.698 and 0.789,respectively.Conclusion Whole-brain CTP can predict the occurrence of DCI at admission and diagnose DCI during DCITW.The extreme quantitative parameters and qualitative color-coded perfusion maps can better reflect the perfusion changes of patients with DCI from admission to DCITW.
基金supported by the National Natural Science Foundation of China,No.81730050(to WH).
文摘In vivo imaging of cerebral ischemia/reperfusion injury remains an important challenge.We injected porous Ag/Au@SiO_(2) bimetallic hollow nanoshells carrying anti-tropomyosin 4 as a molecular probe into mice with cerebral ischemia/reperfusion injury and observed microvascular changes in the brain using photoacoustic imaging with ultrasonography.At each measured time point,the total photoacoustic signal was significantly higher on the affected side than on the healthy side.Twelve hours after reperfusion,cerebral perfusion on the affected side increased,cerebrovascular injury worsened,and anti-tropomyosin 4 expression increased.Twenty-four hours after reperfusion and later,perfusion on the affected side declined slowly and stabilized after 1 week;brain injury was also alleviated.Histopathological and immunohistochemical examinations confirmed the brain injury tissue changes.The nanoshell molecular probe carrying anti-tropomyosin 4 has potential for use in early diagnosis of cerebral ischemia/reperfusion injury and evaluating its progression.
基金supported by the Natural Science Foundation of Guangdong Province(Grant No.2020A151501287)the General Project of Science and Technology Innovation Commission of Shenzhen(Grant Nos.JCYJ20210324134800001,JCYJ20190808103401655)+1 种基金Basic Public Welfare Research Project of Zhejiang Province(Grant No.LGF21H090011)the National Natural Science Foundation of China(Grant No.82174132).
文摘Ischemic cerebrovascular disease is a leading cause of death globally and is often exacerbated by cerebral ischemic/reperfusion injury(CIRI).The exact mechanisms underlying I/R injury are unclear.In this study,we aimed to determine the role of m6A-modified methylase complex methyltransferase-like 3(METTL3)in cerebral ischemiareperfusion(I/R)injury.We found that m6A and METTL3 levels increased in OGD/RX-induced mouse astrocytescerebellar(MA-C)and the brain of middle cerebral artery occlusion(MCAO)model mice.METTL3 siRNA treatment reduced OGD-RX-induced MAC cell viability and proliferation,which increased with METTL3 over-expression.Flow cytometry analysis showed that silencing METTL3 significantly enhanced OGD/RX-induced MAC apoptosis,which was significantly reduced with METTL3 up-regulation.In an MCAO model,METTL3 overexpression significantly reduced cerebral infarction area and decreased brain cell apoptosis,indicating that METTL3 OE treatment could ameliorate brain edema and injury.Thus,METTL3 could be used as a target to treat I/R injury.
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.
