Experimental stroke research commonly employs focal cerebral ischemic rat models （Bederson et al., 1986a; Longa et al., 1989）. In human patients, ischemic stroke typically results from thrombotic or embolic occlusio...Experimental stroke research commonly employs focal cerebral ischemic rat models （Bederson et al., 1986a; Longa et al., 1989）. In human patients, ischemic stroke typically results from thrombotic or embolic occlusion of a major cerebral artery, usually the mid- dle cerebral artery （MCA）. Experimental focal cerebral ischemia models have been employed to mimic human stroke （Durukan and Tatlisumak, 2007）. Rodent models of focal cerebral ischemia that do not require craniotomy have been developed using intraluminal suture occlusion of the MCA （MCA occlusion, MCAO） （Rosamond et al., 2008）. Furthermore, mouse MCAO models have been wide- ly used and extended to genetic studies of cell death or recovery mechanisms （Liu and McCullough, 2011）. Genetically engineered mouse stroke models are particularly useful for evaluation of isch- emic pathophysiology and the design of new prophylactic, neuro- protective, and therapeutic agents and interventions （Armstead et al., 2010）. During the past two decades, MCAO surgical techniques have been developed that do not reveal surgical techniques for mouse MCAO model engineering. Therefore, we compared MCAO surgical methods in rats and mice.展开更多
BACKGROUND The 2018 American Heart Association/American Stroke Association guidelines for early management of acute ischemic stroke recommend the use of retrievable stents for mechanical thrombectomy in patients with ...BACKGROUND The 2018 American Heart Association/American Stroke Association guidelines for early management of acute ischemic stroke recommend the use of retrievable stents for mechanical thrombectomy in patients with acute internal carotid artery or middle cerebral artery M1 occlusion that can be treated within 6 h from onset.For cases of carotid artery with ipsilateral middle cerebral artery tandem embolization, the operation is more complicated and challenging. We here report a case of a tandem embolism, and the anatomy of the aortic arch was complex.Direct carotid artery incision and thrombectomy can not only prevent the escape of the carotid embolus but also save time during establishment of the thrombectomy access.CASE SUMMARY The patient was a 70-year-old man. He was admitted to hospital due to sudden inability to speak and inability to move his right limb for 3 h. Imaging confirmed a diagnosis of a tandem embolism in the left carotid artery with left M1 occlusion.Carotid artery incision thrombectomy combined with stent thrombectomy was performed. The operation was successful, and 24 h later the patient was conscious and mentally competent but had motor aphasia. His bilateral limb muscle strength level was 5, and his neurologic severity scores score was 2.CONCLUSION Carotid artery incision thrombectomy combined with stenting for carotid artery plus cerebral artery tandem embolization is clinically feasible. For patients with a complicated aortic arch and an extremely tortuous carotid artery, carotid artery incision can be chosen to establish the interventional path.展开更多
The purpose of this work was to demonstrate the feasibility of neurite orientation dispersion and density imaging(NODDI)in characterizing the brain tissue microstructural changes of middle cerebral artery occlusion(MC...The purpose of this work was to demonstrate the feasibility of neurite orientation dispersion and density imaging(NODDI)in characterizing the brain tissue microstructural changes of middle cerebral artery occlusion(MCAO)in rats at 3T MRI,and to validate NODDI metrics with histology.A multi-shell diffusion MRI protocol was performed on 11 MCAO rats and 10 control rats at different post-operation time points of 0.5,2,6,12,24 and 72 h.NODDI orientation dispersion index(ODI)and intracellular volume fraction(V_(ic))metrics were compared between MCAO group and control group.The evolution of NODDI metrics was characterized and validated by histology.Infarction was consistent with significantly increased ODI and V_(ic)in comparison to control tissues at all time points(P<0.001).Lesion ODI increased gradually from 0.5 to 72 h,while its V_(ic)showed a more complicated and fluctuated evolution.ODI and V_(ic)were significantly different between hyperacute and acute stroke periods(P<0.001).The NODDI metrics were found to be consistent with the histological findings.In conclusion,NODDI can reflect microstructural changes of brain tissues in MCAO rats at 3T MRI and the metrics are consistent with histology.This study helps to prepare NODDI for the diagnosis and management of ischemic stroke in translational research and clinical practice.展开更多
Rodents have been widely used in the production of cerebral ischemia models. However, successful therapies have been proven on experimental rodent stroke model, and they have often failed to be effective when tested c...Rodents have been widely used in the production of cerebral ischemia models. However, successful therapies have been proven on experimental rodent stroke model, and they have often failed to be effective when tested clinically. Therefore, nonhuman primates were recommended as the ideal alternatives, owing to their similarities with the human cerebrovascular system, brain metabolism, grey to white matter ratio and even their rich behavioral repertoire. The present review is a thorough summary of ten methods that establish nonhuman primate models of focal cerebral ischemia; electrocoagulation, endothelin-1-induced occlusion, microvascular clip occlusion, autologous blood clot embolization, balloon inflation, microcatheter embolization, coil embolization, surgical suture embolization, suture, and photochemical induction methods. This review addresses the advantages and disadvantages of each method, as well as precautions for each model, compared nonhuman primates with rodents, different species of nonhuman primates and different modeling methods. Finally it discusses various factors that need to be considered when modelling and the method of evaluation after modelling. These are critical for understanding their respective strengths and weaknesses and underlie the selection of the optimum model.展开更多
Angiopoietin-1/tyrosine kinase with immunoglobulin and epidermal growth factor homology domains 2 （Tie-2） is a newly discovered signaling pathway of angiogenesis. Angiogenesis benefits recovery of neurological funct...Angiopoietin-1/tyrosine kinase with immunoglobulin and epidermal growth factor homology domains 2 （Tie-2） is a newly discovered signaling pathway of angiogenesis. Angiogenesis benefits recovery of neurological functions such as swallowing. In the present study, a rat model of dysphagia following stroke was induced by middle cerebral artery occlusion to investigate the influence of low frequency electrical stimulus with bidirectional square waves and triangular waves on angiopoietin-1/-13e-2 mRNA expression. Reverse transcription-polymerase chain reaction results showed that low frequency electrical stimulus significantly improved the neurological scores of the model rats, and increased angiopoietin-1/＇13e-2 mRNA expression. This demonstrates that low frequency electrical stimulation can ameliorate neurological function in rats with focal brain ischemia, potentially through regulation of angiopoietin-1/-13e-2 expression in the angiogenesis pathway.展开更多
Baicalin, a flavonoid compound from the root of the herb Scutellaria baicalensis Georgi, has been widely used to treat patients with inflammatory disease. The aim of this study was to assess the efficacy of baicalin i...Baicalin, a flavonoid compound from the root of the herb Scutellaria baicalensis Georgi, has been widely used to treat patients with inflammatory disease. The aim of this study was to assess the efficacy of baicalin in a rat model of focal cerebral ischemia. Adult male Sprague-Dawley rat models of cerebral artery occlusion were established and then randomly and equally divided into three groups： ischemia（cerebral ischemia and reperfusion）, valproic acid（cerebral ischemia and reperfusion ＋ three intraperitoneal injections of valproic acid; positive control）, and baicalin（cerebral ischemia and reperfusion ＋ intraperitoneal injection of baicalin for 21 days）. Neurological deficits were assessed using the postural reflex test and forelimb placing test at 3, 7, 14, and 21 days after ischemia. Rat cerebral infarct volume was measured using 2,3,5-triphenyltetrazolium chloride（TTC） staining method. Pathological change of ischemic brain tissue was assessed using hematoxylin-eosin staining. In the baicalin group, rat neurological function was obviously improved, cerebral infarct volume was obviously reduced, and the pathological impairment of ischemic brain tissue was obviously alleviated compared to the ischemia group. Cerebral infarct volume was similar in the valproic acid and baicalin groups. These findings suggest that baicalin has a neuroprotective effect on cerebral ischemia.展开更多
Endovascular surgery is advantageous in experimentally induced ischemic stroke because it causes fewer cranial traumatic lesions than invasive surgery and can closely mimic the pathophysiology in stroke patients. Howe...Endovascular surgery is advantageous in experimentally induced ischemic stroke because it causes fewer cranial traumatic lesions than invasive surgery and can closely mimic the pathophysiology in stroke patients. However, the outcomes are highly variable, which limits the accuracy of evaluations of ischemic stroke studies. In this study, eight healthy adult rhesus monkeys were randomized into two groups with four monkeys in each group： middle cerebral artery occlusion at origin segment （M1） and middle cerebral artery occlusion at M2 segment. The blood flow in the middle cerebral artery was blocked completely for 2 hours using the endovascular microcoil placement technique （1 mm × 10 cm） （undetachable）, to establish a model of cerebral ischemia. The microcoil was withdrawn and the middle cerebral artery blood flow was restored. A reversible middle cerebral artery occlusion model was identified by hematoxylin-eosin staining, digital subtraction angiography, magnetic resonance angiography, magnetic resonance imaging, and neurological evaluation. The results showed that the middle cerebral artery occlusion model was successfully established in eight adult healthy rhesus monkeys, and ischemic lesions were apparent in the brain tissue of rhesus monkeys at 24 hours after occlusion. The rhesus monkeys had symptoms of neurological deficits. Compared with the M1 occlusion group, the M2 occlusion group had lower infarction volume and higher neurological scores. These experimental findings indicate that reversible middle cerebral artery occlusion can be produced with the endovascular microcoil technique in rhesus monkeys. The M2 occluded model had less infarction and less neurological impairment, which offers the potential for application in the field of brain injury research.展开更多
Background A new lacunar infarction model was recently established in beagle dogs through proximal middle cerebral artery （MCA） occlusion by thrombus. This study aimed to characterize the model by multimodal magneti...Background A new lacunar infarction model was recently established in beagle dogs through proximal middle cerebral artery （MCA） occlusion by thrombus. This study aimed to characterize the model by multimodal magnetic resonance imaging （MRI） and to investigate its potential role for the future stroke research. Methods The left proximal MCA was embolized with an autologous thrombus in six beagles. Diffusion-weighted imaging （DWI） and T2-weighted imaging （T2Wl） were performed every half hour during the first six hours after occlusion, followed by three time points at 12 hours, 24 hours, and one week. Perfusion-weighted imaging （PWI） and magnetic resonance angiography （MRA） were carried out at six hours, 24 hours and one week. The PWI-DWI mismatch ratio was defined as （PWI-DWl）/DWl ischemic volume. Results Lacunar infarcts induced by MCA occlusion were located in the left caudate nucleus and internal capsule. All the lesions could be detected within two hours by DWI. Lesion volume on DWl increased in a time dependent manner, from （87.19±67.16） mm3 at one hour up to （368.98±217.05） mm3 at 24 hours （P=0.009）, while that on PWl gradually decreased from （7315.00±2054.38） mm3at six hours to （4900.33±1319.71） mm3 at 24 hours and （3334.33±1195.11） mm3 at one week （P=0.002）. The mismatch ratio was 41.93±22.75 at six hours after ischemia, showing ＂extensive mismatch＂, and decreased to 18.10±13.74 at 24 hours （P=0.002）. No MCA recanalization was observed within 24 hours after MCA occlusion. Conclusions Lacunar infarction induced by proximal MCA occlusion could be detected early by DWl and was characterized by extensive PWI-DWl mismatch. Multimodal MRI is useful to demonstrate the natural evolution of PWI-DWl mismatch. This ischemic model could be further used for investigating early thrombolysis in lacunar stroke showing extensive mismatch.展开更多
The present study aimed to explore the mechanism underlying the protective effects of hydrogen sulfide against neuronal damage caused by cerebral ischemia/reperfusion. We established the middle cerebral artery occlusi...The present study aimed to explore the mechanism underlying the protective effects of hydrogen sulfide against neuronal damage caused by cerebral ischemia/reperfusion. We established the middle cerebral artery occlusion model in rats via the suture method. Ten minutes after middle cerebral artery occlusion, the animals were intraperitoneally injected with hydrogen sulfide donor compound sodium hydrosulfide. Immunofluorescence revealed that the immunoreactivity of P2X7 in the cerebral cortex and hippocampal CA1 region in rats with cerebral ischemia/reperfusion injury decreased with hydrogen sulfide treatment. Furthermore, treatment of these rats with hydrogen sulfide significantly lowered mortality, the Longa neurological deficit scores, and infarct volume. These results indicate that hydrogen sulfide may be protective in rats with local cerebral ischemia/reperfusion injury by down-regulating the expression of P2X7 receptors.展开更多
Reperfusion therapy is the preferred treatment for ischemic stroke,but is hindered by its short treatment window,especially in patients with diabetes whose reperfusion after prolonged ischemia is often accompanied by ...Reperfusion therapy is the preferred treatment for ischemic stroke,but is hindered by its short treatment window,especially in patients with diabetes whose reperfusion after prolonged ischemia is often accompanied by exacerbated hemorrhage.The mechanisms underlying exacerbated hemorrhage are not fully understood.This study aimed to identify this mechanism by inducing prolonged 2-hour transient intraluminal middle cerebral artery occlusion in diabetic Ins2Akita/+mice to mimic patients with diabetes undergoing delayed mechanical thrombectomy.The results showed that at as early as 2 hours after reperfusion,Ins2Akita/+mice exhibited rapid development of neurological deficits,increased infarct and hemorrhagic transformation,together with exacerbated down-regulation of tight-junction protein ZO-1 and upregulation of blood-brain barrier-disrupting matrix metallopeptidase 2 and matrix metallopeptidase 9 when compared with normoglycemic Ins2+/+mice.This indicated that diabetes led to the rapid compromise of vessel integrity immediately after reperfusion,and consequently earlier death and further aggravation of hemorrhagic transformation 22 hours after reperfusion.This observation was associated with earlier and stronger up-regulation of pro-angiogenic vascular endothelial growth factor(VEGF)and its downstream phospho-Erk1/2 at 2 hours after reperfusion,which was suggestive of premature angiogenesis induced by early VEGF up-regulation,resulting in rapid vessel disintegration in diabetic stroke.Endoplasmic reticulum stress-related pro-apoptotic C/EBP homologous protein was overexpressed in challenged Ins2Akita/+mice,which suggests that the exacerbated VEGF up-regulation may be caused by overwhelming endoplasmic reticulum stress under diabetic conditions.In conclusion,the results mimicked complications in patients with diabetes undergoing delayed mechanical thrombectomy,and diabetes-induced accelerated VEGF up-regulation is likely to underlie exacerbated hemorrhagic transformation.Thus,suppression of the VEGF pathway could be a potential approach to allow reperfusion therapy in patients with diabetic stroke beyond the current treatment window.Experiments were approved by the Committee on the Use of Live Animals in Teaching and Research of the University of Hong Kong[CULATR 3834-15(approval date January 5,2016);3977-16(approval date April 13,2016);and 4666-18(approval date March 29,2018)].展开更多
基金supported by the 2013 Inje University Research Grant
文摘Experimental stroke research commonly employs focal cerebral ischemic rat models （Bederson et al., 1986a; Longa et al., 1989）. In human patients, ischemic stroke typically results from thrombotic or embolic occlusion of a major cerebral artery, usually the mid- dle cerebral artery （MCA）. Experimental focal cerebral ischemia models have been employed to mimic human stroke （Durukan and Tatlisumak, 2007）. Rodent models of focal cerebral ischemia that do not require craniotomy have been developed using intraluminal suture occlusion of the MCA （MCA occlusion, MCAO） （Rosamond et al., 2008）. Furthermore, mouse MCAO models have been wide- ly used and extended to genetic studies of cell death or recovery mechanisms （Liu and McCullough, 2011）. Genetically engineered mouse stroke models are particularly useful for evaluation of isch- emic pathophysiology and the design of new prophylactic, neuro- protective, and therapeutic agents and interventions （Armstead et al., 2010）. During the past two decades, MCAO surgical techniques have been developed that do not reveal surgical techniques for mouse MCAO model engineering. Therefore, we compared MCAO surgical methods in rats and mice.
文摘BACKGROUND The 2018 American Heart Association/American Stroke Association guidelines for early management of acute ischemic stroke recommend the use of retrievable stents for mechanical thrombectomy in patients with acute internal carotid artery or middle cerebral artery M1 occlusion that can be treated within 6 h from onset.For cases of carotid artery with ipsilateral middle cerebral artery tandem embolization, the operation is more complicated and challenging. We here report a case of a tandem embolism, and the anatomy of the aortic arch was complex.Direct carotid artery incision and thrombectomy can not only prevent the escape of the carotid embolus but also save time during establishment of the thrombectomy access.CASE SUMMARY The patient was a 70-year-old man. He was admitted to hospital due to sudden inability to speak and inability to move his right limb for 3 h. Imaging confirmed a diagnosis of a tandem embolism in the left carotid artery with left M1 occlusion.Carotid artery incision thrombectomy combined with stent thrombectomy was performed. The operation was successful, and 24 h later the patient was conscious and mentally competent but had motor aphasia. His bilateral limb muscle strength level was 5, and his neurologic severity scores score was 2.CONCLUSION Carotid artery incision thrombectomy combined with stenting for carotid artery plus cerebral artery tandem embolization is clinically feasible. For patients with a complicated aortic arch and an extremely tortuous carotid artery, carotid artery incision can be chosen to establish the interventional path.
基金National Natural Science Foundation of China(No.81570462,No.81730049,and No.81801666).
文摘The purpose of this work was to demonstrate the feasibility of neurite orientation dispersion and density imaging(NODDI)in characterizing the brain tissue microstructural changes of middle cerebral artery occlusion(MCAO)in rats at 3T MRI,and to validate NODDI metrics with histology.A multi-shell diffusion MRI protocol was performed on 11 MCAO rats and 10 control rats at different post-operation time points of 0.5,2,6,12,24 and 72 h.NODDI orientation dispersion index(ODI)and intracellular volume fraction(V_(ic))metrics were compared between MCAO group and control group.The evolution of NODDI metrics was characterized and validated by histology.Infarction was consistent with significantly increased ODI and V_(ic)in comparison to control tissues at all time points(P<0.001).Lesion ODI increased gradually from 0.5 to 72 h,while its V_(ic)showed a more complicated and fluctuated evolution.ODI and V_(ic)were significantly different between hyperacute and acute stroke periods(P<0.001).The NODDI metrics were found to be consistent with the histological findings.In conclusion,NODDI can reflect microstructural changes of brain tissues in MCAO rats at 3T MRI and the metrics are consistent with histology.This study helps to prepare NODDI for the diagnosis and management of ischemic stroke in translational research and clinical practice.
基金supported by the National Natural Science Foundation of China,No.81000852 and 81301677the AHA Award,No.17POST32530004+1 种基金the Supporting Project of Science & Technology of Sichuan Province of China,No.2012SZ0140the Research Foundation of Zhejiang Province of China,No.201022896
文摘Rodents have been widely used in the production of cerebral ischemia models. However, successful therapies have been proven on experimental rodent stroke model, and they have often failed to be effective when tested clinically. Therefore, nonhuman primates were recommended as the ideal alternatives, owing to their similarities with the human cerebrovascular system, brain metabolism, grey to white matter ratio and even their rich behavioral repertoire. The present review is a thorough summary of ten methods that establish nonhuman primate models of focal cerebral ischemia; electrocoagulation, endothelin-1-induced occlusion, microvascular clip occlusion, autologous blood clot embolization, balloon inflation, microcatheter embolization, coil embolization, surgical suture embolization, suture, and photochemical induction methods. This review addresses the advantages and disadvantages of each method, as well as precautions for each model, compared nonhuman primates with rodents, different species of nonhuman primates and different modeling methods. Finally it discusses various factors that need to be considered when modelling and the method of evaluation after modelling. These are critical for understanding their respective strengths and weaknesses and underlie the selection of the optimum model.
基金the National High-Tech R&D Program of China (863 Program), No.2007AA022Z482
文摘Angiopoietin-1/tyrosine kinase with immunoglobulin and epidermal growth factor homology domains 2 （Tie-2） is a newly discovered signaling pathway of angiogenesis. Angiogenesis benefits recovery of neurological functions such as swallowing. In the present study, a rat model of dysphagia following stroke was induced by middle cerebral artery occlusion to investigate the influence of low frequency electrical stimulus with bidirectional square waves and triangular waves on angiopoietin-1/-13e-2 mRNA expression. Reverse transcription-polymerase chain reaction results showed that low frequency electrical stimulus significantly improved the neurological scores of the model rats, and increased angiopoietin-1/＇13e-2 mRNA expression. This demonstrates that low frequency electrical stimulation can ameliorate neurological function in rats with focal brain ischemia, potentially through regulation of angiopoietin-1/-13e-2 expression in the angiogenesis pathway.
基金supported by the Cross Foundation Major Project of Engineering and Medicine of Shanghai Jiao Tong University,No.YG2016MS50(to JD)Foundation for Fostering Project of Clinical Study on Multi-disciplinary Team of Renji Hospital,No.PYMDT-012(to JD)
文摘Baicalin, a flavonoid compound from the root of the herb Scutellaria baicalensis Georgi, has been widely used to treat patients with inflammatory disease. The aim of this study was to assess the efficacy of baicalin in a rat model of focal cerebral ischemia. Adult male Sprague-Dawley rat models of cerebral artery occlusion were established and then randomly and equally divided into three groups： ischemia（cerebral ischemia and reperfusion）, valproic acid（cerebral ischemia and reperfusion ＋ three intraperitoneal injections of valproic acid; positive control）, and baicalin（cerebral ischemia and reperfusion ＋ intraperitoneal injection of baicalin for 21 days）. Neurological deficits were assessed using the postural reflex test and forelimb placing test at 3, 7, 14, and 21 days after ischemia. Rat cerebral infarct volume was measured using 2,3,5-triphenyltetrazolium chloride（TTC） staining method. Pathological change of ischemic brain tissue was assessed using hematoxylin-eosin staining. In the baicalin group, rat neurological function was obviously improved, cerebral infarct volume was obviously reduced, and the pathological impairment of ischemic brain tissue was obviously alleviated compared to the ischemia group. Cerebral infarct volume was similar in the valproic acid and baicalin groups. These findings suggest that baicalin has a neuroprotective effect on cerebral ischemia.
基金supported by grants from the National Key Basic Research Program(973 Program)of China,No.2011CB707804Beijing Municipal Science and Technology Project,No.2121100005312016
文摘Endovascular surgery is advantageous in experimentally induced ischemic stroke because it causes fewer cranial traumatic lesions than invasive surgery and can closely mimic the pathophysiology in stroke patients. However, the outcomes are highly variable, which limits the accuracy of evaluations of ischemic stroke studies. In this study, eight healthy adult rhesus monkeys were randomized into two groups with four monkeys in each group： middle cerebral artery occlusion at origin segment （M1） and middle cerebral artery occlusion at M2 segment. The blood flow in the middle cerebral artery was blocked completely for 2 hours using the endovascular microcoil placement technique （1 mm × 10 cm） （undetachable）, to establish a model of cerebral ischemia. The microcoil was withdrawn and the middle cerebral artery blood flow was restored. A reversible middle cerebral artery occlusion model was identified by hematoxylin-eosin staining, digital subtraction angiography, magnetic resonance angiography, magnetic resonance imaging, and neurological evaluation. The results showed that the middle cerebral artery occlusion model was successfully established in eight adult healthy rhesus monkeys, and ischemic lesions were apparent in the brain tissue of rhesus monkeys at 24 hours after occlusion. The rhesus monkeys had symptoms of neurological deficits. Compared with the M1 occlusion group, the M2 occlusion group had lower infarction volume and higher neurological scores. These experimental findings indicate that reversible middle cerebral artery occlusion can be produced with the endovascular microcoil technique in rhesus monkeys. The M2 occluded model had less infarction and less neurological impairment, which offers the potential for application in the field of brain injury research.
基金This study was supported by the National Natural Science Foundation of China （No. 30870710, No. 81000653） and the Foundation of Research and Innovation Program for Postgraduates in Jiangsu Province （No. CXZZll.0718）.
文摘Background A new lacunar infarction model was recently established in beagle dogs through proximal middle cerebral artery （MCA） occlusion by thrombus. This study aimed to characterize the model by multimodal magnetic resonance imaging （MRI） and to investigate its potential role for the future stroke research. Methods The left proximal MCA was embolized with an autologous thrombus in six beagles. Diffusion-weighted imaging （DWI） and T2-weighted imaging （T2Wl） were performed every half hour during the first six hours after occlusion, followed by three time points at 12 hours, 24 hours, and one week. Perfusion-weighted imaging （PWI） and magnetic resonance angiography （MRA） were carried out at six hours, 24 hours and one week. The PWI-DWI mismatch ratio was defined as （PWI-DWl）/DWl ischemic volume. Results Lacunar infarcts induced by MCA occlusion were located in the left caudate nucleus and internal capsule. All the lesions could be detected within two hours by DWI. Lesion volume on DWl increased in a time dependent manner, from （87.19±67.16） mm3 at one hour up to （368.98±217.05） mm3 at 24 hours （P=0.009）, while that on PWl gradually decreased from （7315.00±2054.38） mm3at six hours to （4900.33±1319.71） mm3 at 24 hours and （3334.33±1195.11） mm3 at one week （P=0.002）. The mismatch ratio was 41.93±22.75 at six hours after ischemia, showing ＂extensive mismatch＂, and decreased to 18.10±13.74 at 24 hours （P=0.002）. No MCA recanalization was observed within 24 hours after MCA occlusion. Conclusions Lacunar infarction induced by proximal MCA occlusion could be detected early by DWl and was characterized by extensive PWI-DWl mismatch. Multimodal MRI is useful to demonstrate the natural evolution of PWI-DWl mismatch. This ischemic model could be further used for investigating early thrombolysis in lacunar stroke showing extensive mismatch.
基金financially supported by grants from the National Natural Science Foundation of China,No.81371346,81271376Outstanding Postgraduate Fund of Xinxiang Medical UniversityScience and Technology Key Research Project of Henan Provincial Education Department of China,No.14A310019
文摘The present study aimed to explore the mechanism underlying the protective effects of hydrogen sulfide against neuronal damage caused by cerebral ischemia/reperfusion. We established the middle cerebral artery occlusion model in rats via the suture method. Ten minutes after middle cerebral artery occlusion, the animals were intraperitoneally injected with hydrogen sulfide donor compound sodium hydrosulfide. Immunofluorescence revealed that the immunoreactivity of P2X7 in the cerebral cortex and hippocampal CA1 region in rats with cerebral ischemia/reperfusion injury decreased with hydrogen sulfide treatment. Furthermore, treatment of these rats with hydrogen sulfide significantly lowered mortality, the Longa neurological deficit scores, and infarct volume. These results indicate that hydrogen sulfide may be protective in rats with local cerebral ischemia/reperfusion injury by down-regulating the expression of P2X7 receptors.
基金supported by Health and Medical Research Fund,the Food and Health Bureau,The Government of the Hong Kong Special Administrative Region(03142256)General Research Fund,Hong Kong Research Grants Council(GRF#HKU773613M)+1 种基金Seed Funding Programme for Basic Research(201811159123,201910159191)The University of Hong Kong(all to ACYL)。
文摘Reperfusion therapy is the preferred treatment for ischemic stroke,but is hindered by its short treatment window,especially in patients with diabetes whose reperfusion after prolonged ischemia is often accompanied by exacerbated hemorrhage.The mechanisms underlying exacerbated hemorrhage are not fully understood.This study aimed to identify this mechanism by inducing prolonged 2-hour transient intraluminal middle cerebral artery occlusion in diabetic Ins2Akita/+mice to mimic patients with diabetes undergoing delayed mechanical thrombectomy.The results showed that at as early as 2 hours after reperfusion,Ins2Akita/+mice exhibited rapid development of neurological deficits,increased infarct and hemorrhagic transformation,together with exacerbated down-regulation of tight-junction protein ZO-1 and upregulation of blood-brain barrier-disrupting matrix metallopeptidase 2 and matrix metallopeptidase 9 when compared with normoglycemic Ins2+/+mice.This indicated that diabetes led to the rapid compromise of vessel integrity immediately after reperfusion,and consequently earlier death and further aggravation of hemorrhagic transformation 22 hours after reperfusion.This observation was associated with earlier and stronger up-regulation of pro-angiogenic vascular endothelial growth factor(VEGF)and its downstream phospho-Erk1/2 at 2 hours after reperfusion,which was suggestive of premature angiogenesis induced by early VEGF up-regulation,resulting in rapid vessel disintegration in diabetic stroke.Endoplasmic reticulum stress-related pro-apoptotic C/EBP homologous protein was overexpressed in challenged Ins2Akita/+mice,which suggests that the exacerbated VEGF up-regulation may be caused by overwhelming endoplasmic reticulum stress under diabetic conditions.In conclusion,the results mimicked complications in patients with diabetes undergoing delayed mechanical thrombectomy,and diabetes-induced accelerated VEGF up-regulation is likely to underlie exacerbated hemorrhagic transformation.Thus,suppression of the VEGF pathway could be a potential approach to allow reperfusion therapy in patients with diabetic stroke beyond the current treatment window.Experiments were approved by the Committee on the Use of Live Animals in Teaching and Research of the University of Hong Kong[CULATR 3834-15(approval date January 5,2016);3977-16(approval date April 13,2016);and 4666-18(approval date March 29,2018)].
