Objective:To understand the clinical characteristics of patients with embryonic posterior cerebral artery and its correlation with abnormal vascular development.Methods:The clinical data of 396 patients with embryonic...Objective:To understand the clinical characteristics of patients with embryonic posterior cerebral artery and its correlation with abnormal vascular development.Methods:The clinical data of 396 patients with embryonic posterior cerebral artery confirmed by magnetic resonance angiography(MRA)and computed tomography angiography(CTA)were analyzed.Results:Two-hundred patients had clinical manifestations of posterior circulation ischemia,including recurrent dizziness,vertigo,and tinnitus;45 had headaches,97 had limb weakness,and 16 patients had syncope or impaired consciousness.Seventy-six patients with circulatory infarction were admitted to the hospital.There were 251 patients with history of hypertension,74 with diabetes,113 with hyperlipidemia,13 with dominant vertebral artery,10 with intracranial aneurysm,and 19 with absence of A1 segment of the anterior cerebral artery(considering developmental variation).Conclusion:Embryonic posterior cerebral artery develops abnormally during the embryonic period,often accompanied by abnormal vascular access.Due to abnormal hemodynamics,the incidence of posterior circulation ischemia,aneurysm,and infarction increases in such patients.展开更多
Fluid-attenuated inversion recovery(FLAIR) vascular hyperintensity(FVH) is used to assess leptomeningeal collateral circulation, but clinical outcomes of patients with FVH can be very different. The aim of the present...Fluid-attenuated inversion recovery(FLAIR) vascular hyperintensity(FVH) is used to assess leptomeningeal collateral circulation, but clinical outcomes of patients with FVH can be very different. The aim of the present study was to assess a FVH score and explore its relationship with clinical outcomes. Patients with acute ischemic stroke due to middle cerebral artery M1 occlusion underwent magnetic resonance imaging and were followed up at 10 days(National Institutes of Health Stroke Scale) and 90 days(modified Rankin Scale) to determine short-term clinical outcomes. Effective collateral circulation indirectly improved recovery of neurological function and short-term clinical outcome by extending the size of the pial penumbra and reducing infarct lesions. FVH score showed no correlation with 90-day functional clinical outcome and was not sufficient as an independent predictor of short-term clinical outcome.展开更多
Objective:Longshengzhi capsule(LSZC)is an optimized preparation based on the traditional Chinese Medicine formula Buyanghuanwu Decoction(BYHWD),and is approved by the China Food and Drug Administration for treating st...Objective:Longshengzhi capsule(LSZC)is an optimized preparation based on the traditional Chinese Medicine formula Buyanghuanwu Decoction(BYHWD),and is approved by the China Food and Drug Administration for treating stroke-induced disability and vascular diseases.Herein,we examined the pharmacodynamics,anti-apoptotic and anti-oxidant actions,and potential mechanisms of action of LSZC following stroke in rats.Methods:Permanent middle cerebral artery occlusion(MCAO)was used as an ischemic stroke model.LSZC was administered intragastrically.We examined the survival rate,bodyweight,and neurological deficits in stroke rats.Brain infarct size was determined by 2,3,5-triphenyltetrazolium chloride staining.Brain pathology was examined using hematoxylin and eosin staining,Nissl staining,and TdT-mediated dUTP Nick-End Labeling staining.Malondialdehyde,catalase,superoxide dismutase,and glutathione levels were examined by commercial kits.Expression of Nrf2,heme oxygenase-1,Bax,Bcl-2,cleaved caspase-3,and caspase-3 proteins in brain tissue was measured by Western blot.Results:LSZC markedly improved the survival rate and bodyweight,and reduced infarct volume and neurological deficit scores,in MCAO stroke rats.LSZC also significantly attenuated oxidative stress,as indicated by decreased expression of malondialdehyde,and upregulation of Nrf2,heme oxygenase-1,catalase,superoxide dismutase,and glutathione.Moreover,LSZC significantly decreased apoptosis,including a decrease in Bax and cleaved caspase-3 expression,and an increase in Bcl-2,as well as a reduction in numbers of apoptotic neurons.Conclusion:LSZC treatment is neuroprotective against ischemic stroke,potentially via reducing oxidative stress and apoptosis.The Nrf2 and apoptotic signaling pathways may play important roles in the antioxidant and anti-apoptotic actions of LSZC.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
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
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
The histopathological features of the middle cerebral artery(MCA) and superficial temporal artery(STA) from moyamoya disease(MMD) and their relationships with gender,age,angiography stage were explored.The causes and ...The histopathological features of the middle cerebral artery(MCA) and superficial temporal artery(STA) from moyamoya disease(MMD) and their relationships with gender,age,angiography stage were explored.The causes and the clinical significance of vasculopathy of STA were also discussed.The clinical data and specimens of MCA and STA from 30 MMD patients were collected.Twelve samples of MCA and STA from non-MMD patients served as control group.Histopathological examination was then performed by measuring the thickness of intima and media,and statistical analysis was conducted.The MCA and STA specimens from MMD group had apparently thicker intima and thinner media than those from the control group.There was no significant pathological difference between the hemorrhage group and non-hemorrhage group,and between the males and females in MMD patients.Neither the age nor the digital subtraction angiography(DSA) stage was correlated with the thickness of intima in MCA and STA.MMD is a systemic vascular disease involving both intracranial and extracranial vessels.Preoperative external carotid arteriography,especially super-selective arteriography of the STA,benefits the selection of donor vessel.展开更多
BACKGROUND Aneurysm compression,diabetes,and traumatic brain injury are well-known causative factors of oculomotor nerve palsy(ONP),while cases of ONP induced by neurovascular conflicts have rarely been reported in th...BACKGROUND Aneurysm compression,diabetes,and traumatic brain injury are well-known causative factors of oculomotor nerve palsy(ONP),while cases of ONP induced by neurovascular conflicts have rarely been reported in the medical community.Here,we report a typical case of ONP caused by right posterior cerebral artery(PCA)compression to increase neurosurgeons’awareness of the disease and reduce misdiagnosis and recurrence.CASE SUMMARY A 54-year-old man without a known medical history presented with right ONP for the past 5 years.The patient presented to the hospital with right ptosis,diplopia,anisocoria(rt 5 mm,lt 2.5 mm),loss of duction in all directions,abduction,and light impaired pupillary reflexes.Magnetic resonance angiography and computed tomography venography examinations showed no phlebangioma,aneurysm,or intracranial lesion.After conducting oral glucose tolerance and prostigmin tests,diabetes and myasthenia gravis were excluded.Cranial nerve magnetic resonance imaging showed that the right PCA loop was in direct contact with the cisternal segment of the right oculomotor nerve(ON).Microvascular decompression(MVD)of the culprit vessel from the ON through a right subtemporal craniotomy was carried out,and the ONP symptoms were significantly relieved after 3 mo.CONCLUSION Vascular compression of the ON is a rare pathogeny of ONP that may be refractory to drug therapy and ophthalmic strabismus surgery.MVD is an effective treatment for ONP induced by neurovascular compression.展开更多
BACKGROUND: Insulin-like growth factor-I(IGF-1), as one of the important members of growth factor family, participants in the regulation of many physiological functions and behaviors, having very strong neuroprotectiv...BACKGROUND: Insulin-like growth factor-I(IGF-1), as one of the important members of growth factor family, participants in the regulation of many physiological functions and behaviors, having very strong neuroprotective effect. However, the expression of IGF-1 following cerebral ischemia/reperfusion is still disputed. OBJECTIVE: To observe the expression of IGF-1 and protein of corpora striata in ischemic side at the early stage of middle cerebral artery ischemia/reperfusion in rhesus monkey. DESIGN: A completely randomized grouping design, controlled animal experiment. SETTING: Institute of Cerebrovascular Disease, Affiliated Hospital of Medical College of Qingdao University. MATERIALS: ① Totally 17 rhesus monkeys , of either gender, aged 4 to 5 years, were enrolled . Seven rhesus monkeys observed with gene chip were randomly divided into 2 groups: sham operation group (n=3) and ischemia/reperfusion group (n=4). Ten rhesus monkeys observed with in situ hybridization and immunohistochemistry method were randomly divided into 2 groups: sham operation group (n=3)and ischemia/reperfusion group (n=7). Rhesus monkeys observed under microscope were divided into 2 groups: sham operation group (n=6) and ischamia/reperfusion group (n=11). ② Materials used in the experiment: cresyl violet (Sigma Company, America); immunohistochemical reagent kit ( Huamei Bio-engineering Company); In situ hybridization reagent kit (Boshide Bio-engineering Co.Ltd, Wuhan); 12 800 dots chip (Boxing Company, Shanghai). METHODS: This experiment was carried out at the Institute of Cerebrovascular Disease, Affiliated Hospital of Medical College of Qingdao University from January 2001 to December 2003. ① The onset area of middle cerebral artery was blocked for 2 hours, middle cerebral artery ischemia/reperfusion models were created. ② After ischemia/reperfusion for 24 hours, cerebral tissue sections of rhesus monkeys were prepared and stained with cresyl violet. Image analysis was performed with 500IW image analysis software. Morphological change of corpora striata of operative side was observed in the rhesus monkeys between two groups. Total RNA was extracted from cerebral tissue. ③ Detection of gene chip: Cy3-duTP and Cy5-duTP were used to respectively perform reverse transcription labeling. The sample was reversely transcribed into cDNA, then hybridized with cDNA of cerebral tissue. Genes with the separate absolute value of cy3 and cy5>800, cy3/cy5 > 2(high expression) or < 0.5 (low expression) were found out. Those were genes with differential expression. ④ The expressions of IGF-1 mRNA and protein level of corpora striata in ischemic side of rhesus monkeys were detected between sham operation group and ischemia/reperfusion group at 9 and 24 hours after ischemia/reperfusion with in situ hybridization method and immunohistochemical method. Brown granules were IGF-1 protein positive cells. ⑤ Analysis of variance was used in the difference comparison of measurement data among groups. MAIN OUTCOME MEASURES: ① Change of morphological structure of corpora striata at ischemic side in rhesus monkeys. ② Change of cerebral gene expression profiles at ischemia/reperfusion in rhesus monkeys between two groups. ③ Expression of IGF-1 mRNA and protein level of corpora striata at ischemia/reperfusion in rhesus monkeys between two groups. RESULTS: ① Pathological change : Obvious pathological change of cerebral infarction appeared in the ischemia and reperfusion group, while there was no such pathological change in the sham operation group. ② Change of gene expression profile : There were 4480 genes with difference expression in the ischemia/reperfusion group and sham-operation group, in which, 260 genes had high expression and their absolute value was over 800, and 63 genes had low expression. cy3/cy5 of IGF-1 was 0.379, being relative low expression. ③ IGF-1 mRNA and protein positive cell counts in corpora striata at cerebral ischemic side[IGF-1 mRNA:(9.72±1.18),(9.11±0.76),(14.77±0.60) counts/field;IGF-1 protein:(15.11±1.83),(15.39±0.78),(34.62±0.97)counts/field,P < 0.05-0.01]. CONCLUSION: IGF-1 mRNA and protein are lowly expressed in middle cerebral artery of rhesus monkeys at ischemia/reperfusion.展开更多
OBJECTIVE To study the role of Ginkgo biloba extract-761(EGb-761)in the recovery of gait abnormality and its neuroprotective effect against the brain injury induced by permanent middle cerebral artery occlu-sion in ra...OBJECTIVE To study the role of Ginkgo biloba extract-761(EGb-761)in the recovery of gait abnormality and its neuroprotective effect against the brain injury induced by permanent middle cerebral artery occlu-sion in rats.METHODS Male Sprague Dawley rats(n=200,240-305 g)were anesthetized with 0.2%pentobarbital sodium diluted in physiological saline(2.0 m L·kg-1,ip).Then a monofilament coated with poly-L-lysine,was used to occlude the origin of the middle cerebral artery.It was inserted into the internal carotid artery lumen until it met mild resistance,approximately 20mm beyond the common carotid artery bifurcation.The suture was secured with a ligature and maintained in place until sacrifice.The same surgical procedure was conducted in sham-operated rats in which the middle cerebral artery was not occluded.Motor and behavioral changes were assessed after surgery using a five point scale.The rats securing the point scale above 2 were included in the study.The rats were randomly divided into control,and treated groups:EGb-761(20,50,and 100 mg·kg-1).The treated groups were oral y administered(10 mL·kg-1)for 28 d.On 7th,14th,21st,and 28th day the neurological scores,rotar rod test and gait assessment(the automated computer-assisted method)were performed.The brains were collected for TTC staining and histopathological analysis.RESULTS 1)Weight:On 28th day,EGb-761(20 mg·kg-1,)significantly increased the weight of the rat by^8%as compared to control(~300 g).However,at 50 mg·kg-1,and 100 mg·kg-1,a significant increase of^7-7.6%(control:~232 g),and^7.3-7%,respectively from 14 to 28 days was noted.2)Neurological scores:On 28thday,EGb-761(20,50,and 100 mg·kg-1)significantly decreased the neurological scores by^18%,~22%,~21%,respectively as compared to control(~2.07).3)Rotar rod test:On 28thday,EGb-761(50,and100 mg·kg-1)significantly increased by^69.1%,~74.1%,respectively as compared to control(~28.2).4)Gait assessment:On 7th,14th,21st,and 28thday,EGb-761(20,50,and 100 m·kg-1)significantly reduced the average body angle,on 7th,14th,21st,and 28thday,EGb-761(100 mg·kg-1)significantly increased the walk speed and reduced the average walking cycle,EGb-761(50,and 100 mg·kg-1)significantly the area of the left brain/right brain area percentage and reduced tissue pathologic neuron injury.CONCLUSION Ginkgo biloba extract EGb-761 has obvious improve behavior disorders,and has a protective neuroprotective effect against the brain injury induced by permanent middle cerebral artery occlusion.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
Cerebral ischemia/reperfusion injury impairs learning and memory in patients.Studies have shown that synaptic function is involved in the formation and development of memory,and that DNA methylation plays a key role i...Cerebral ischemia/reperfusion injury impairs learning and memory in patients.Studies have shown that synaptic function is involved in the formation and development of memory,and that DNA methylation plays a key role in the regulation of learning and memory.To investigate the role of DNA hypomethylation in cerebral ischemia/reperfusion injury,in this study,we established a rat model of cerebral ischemia/reperfusion injury by occlusion of the middle cerebral artery and then treated the rats with intraperitoneal 5-aza-2′-deoxycytidine,an inhibitor of DNA methylation.Our results showed that 5-aza-2′-deoxycytidine markedly improved the neurological function,and cognitive,social and spatial memory abilities,and dose-dependently increased the synaptic density and the expression of SYP and SHANK2 proteins in the hippocampus in a dose-dependent manner in rats with cerebral ischemia/reperfusion injury.The effects of 5-aza-2′-deoxycytidine were closely related to its reduction of genomic DNA methylation and DNA methylation at specific sites of the Syp and Shank2 genes in rats with cerebral ischemia/reperfusion injury.These findings suggest that inhibition of DNA methylation by 5-aza-2′-deoxycytidine promotes the recovery of learning and memory impairment in a rat model of cerebral ischemia/reperfusion injury.These results provide theoretical evidence for stroke treatment using epigenetic methods.展开更多
A 51-year-old man presented with subarachnoid haemorrhage with mild hydrocephaly. Digital substraction angiography and 3-D Computerised Angiogram (CT) revealed a saccular aneurysm at bifurcation of azygos anterior cer...A 51-year-old man presented with subarachnoid haemorrhage with mild hydrocephaly. Digital substraction angiography and 3-D Computerised Angiogram (CT) revealed a saccular aneurysm at bifurcation of azygos anterior cerebral artery (ACA) and other vascular variations such as vertebral artery fenestration and hypoplasia in one anterior cerebral artery. We performed aneurysmal neck clipping with good outcome and postoperative 3-D CT angiogram showed complet obliteration of aneurysm. Although azygos arteries are rare in healthy population, aneurysms of azygos ASA are not rare due to increased haemodynamic stress. We wanted to point out to better visualisation of anatomical variations at 3-D CT angiogram comparing DSA in patients with intracranial aneurysm.展开更多
It is very important to study the factors affecting the incidence,progress and prognosis of patients with vascular dementia.50 cases of severe middle cerebral artery stenosis or occlusion underwent endovascular treatm...It is very important to study the factors affecting the incidence,progress and prognosis of patients with vascular dementia.50 cases of severe middle cerebral artery stenosis or occlusion underwent endovascular treatment(25 cases of mild cognitive dysfunction,25 cases of moderate cognitive dysfunction)were divided into two groups,where a medical drug treatment group and a control group established with 25 cases in each group.The cognitive function of each group of patients was evaluated before operation,7 days after operation,30 days after operation,and 180 days after operation.CTP was used to compare the hemodynamic changes in patients before and after operation.The severe stenosis or occlusion of the middle cerebral artery in patients can be improved,and the intracranial blood supply of patients with poorly compensated medial cranial circulation and hypoperfusion can be restored to a certain extent.Meanwhile,improvement of cognitive function was definitive in some patients with cognitive dysfunction.To guide the formulation of treatment plans for patients with severe middle cerebral artery stenosis or occlusion.展开更多
Objective To report the clinical diagnosis and microsurgical treatment of ruptured distal anterior cerebral artery aneurysm (DACAA) patients treated over the last 3 years. Methods 9 consecutive cases of ruptured DACAA...Objective To report the clinical diagnosis and microsurgical treatment of ruptured distal anterior cerebral artery aneurysm (DACAA) patients treated over the last 3 years. Methods 9 consecutive cases of ruptured DACAA operated from October 2007 to March 2010 were reviewed and followed up. Results 11 aneurysms were clipped展开更多
Prolife ration of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage.Transcranial magnetic stimulation(TMS)has recently emerged as a tool for inducing endogenous ...Prolife ration of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage.Transcranial magnetic stimulation(TMS)has recently emerged as a tool for inducing endogenous neural stem cell regeneration,but its underlying mechanisms remain unclea r In this study,we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem cells.Additionally,repetitive TMS reduced the volume of cerebral infa rction in a rat model of ischemic stro ke caused by middle cerebral artery occlusion,im p roved rat cognitive function,and promoted the proliferation of neural stem cells in the ischemic penumbra.RNA-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ischemia.Furthermore,PCR analysis revealed that repetitive TMS promoted AKT phosphorylation,leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and Cdk4.This effect was also associated with activation of the glycogen synthase kinase 3β/β-catenin signaling pathway,which ultimately promotes the prolife ration of neural stem cells.Subsequently,we validated the effect of repetitive TMS on AKT phosphorylation.We found that repetitive TMS promoted Ca2+influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway,thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3β/β-catenin pathway.These findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+influx-dependent phosphorylated AKT/glycogen synthase kinase 3β/β-catenin signaling pathway.This study has produced pioneering res ults on the intrinsic mechanism of repetitive TMS to promote neural function recove ry after ischemic stro ke.These results provide a stro ng scientific foundation for the clinical application of repetitive TMS.Moreover,repetitive TMS treatment may not only be an efficient and potential approach to support neurogenesis for further therapeutic applications,but also provide an effective platform for the expansion of neural stem cells.展开更多
Some scholars have recently developed the concept of PANoptosis in the study of infectious diseases where pyroptosis,apoptosis and necroptosis act in consort in a multimeric protein complex,PANoptosome.This allows all...Some scholars have recently developed the concept of PANoptosis in the study of infectious diseases where pyroptosis,apoptosis and necroptosis act in consort in a multimeric protein complex,PANoptosome.This allows all the components of PANoptosis to be regulated simultaneously.PANoptosis provides a new way to study the regulation of cell death,in that different types of cell death may be regulated at the same time.To test whether PANoptosis exists in diseases other than infectious diseases,we chose cerebral ischemia/reperfusion injury as the research model,collected articles researching cerebral ischemia/reperfusion from three major databases,obtained the original research data from these articles by bibliometrics,data mining and other methods,then integrated and analyzed these data.We selected papers that investigated at least two of the components of PANoptosis to check its occurrence in ischemia/reperfusion.In the cell model simulating ischemic brain injury,pyroptosis,apoptosis and necroptosis occur together and this phenomenon exists widely in different passage cell lines or primary neurons.Pyroptosis,apoptosis and necroptosis also occurred in rat and mouse models of ischemia/reperfusion injury.This confirms that PANoptosis is observed in ischemic brain injury and indicates that PANoptosis can be a target in the regulation of various central nervous system diseases.展开更多
BACKGROUND:Studies have shown that electro-acupuncture at the Ren meridian could improve proliferation of subventricular zone neural stem cells in cerebral-ischemic rats. However,there are few reports on the influence...BACKGROUND:Studies have shown that electro-acupuncture at the Ren meridian could improve proliferation of subventricular zone neural stem cells in cerebral-ischemic rats. However,there are few reports on the influence of electro-acupuncture at the Du meridian on neural stem cell proliferation. OBJECTIVE:To observe the influence of electro-acupuncture at Ren and Du meridians on neural stem cell proliferation in the subventricular zone and altered signal transduction in cerebral ischemia rats. DESIGN,TIME AND SETTING:A randomized,controlled,animal experiment was performed at the Laboratory of Human Anatomy,Medical College of Sun Yat-sen University from May 2006 to February 2008. MATERIALS:Mouse anti-rat bromodeoxyuridine (BrdU) monoclonal antibody was provided by Sigma,USA; mouse anti-rat nestin monoclonal antibody and extracellular signal-regulated protein kinase (ERK) specific inhibitor PD98059 were provided by Calbiochem,Germany; acupuncture needle was provided by Suzhou Acupuncture Supplies,China. METHODS:A total of 126 rats were randomly assigned to four groups:model (n = 36),Du meridian (n = 36),Ren/Du meridian (n = 36),and Ren/Du meridian + PD98059 (n = 18). Rats in the Ren /Du meridian + PD98059 group were observed on days 7 (n = 6) and 14 (n = 12) after cerebral ischemia injury. Rats in the model,Du meridian,and Ren/Du meridian groups were observed on days 7,14,and 28 after cerebral ischemia injury,with 12 rats per group at each time point. Thread occlusion was used to establish middle cerebral artery occlusion models. Electro-acupuncture was performed at Renzhong (DU 26) and Baihui (DU 20) acupoints in the Du meridian group,as well as Chengjiang (RN 24),Guanyuan (RN 4),Renzhong,and Baihui acupoints in the Ren/Du meridian and Ren/Du meridian + PD98059 groups 2 days after model establishment. In addition,electro-acupuncture stimulation with disperse-dense waves was performed,with 30 Hz disperse wave,100 Hz dense wave,and 5 V intensity for 20 minutes. Rats in the Ren/Du meridian + PD98059 group were treated with 0.2 μg PD98059 injection into the subventricular zone,2 μL per rat. Rats in the model group were not treated with electro-acupuncture. MAIN OUTCOME MEASURES:BrdU/nestin immunofluorescent staining was used to detect proliferating neural stem cells in the subventricular zone of cerebral ischemia rats; Western blot was used to determine phosphorylated ERK1 and 2 (pERK1/2) expression in the subventricular zone. RESULTS:On days 14 and 28 after cerebral ischemia,there were significantly more BrdU-positive and BrdU/nestin-positive cells in the Ren /Du meridian group compared with the Du meridian group (P < 0.05). PD98059 decreased the number of BrdU-positive and BrdU/nestin-positive cells induced by electro-acupuncture at the Ren and Du meridians (P < 0.05). On days 7,14,and 28 after treatment,pERK1/2 expression was significantly greater in the Du meridian and Ren/Du meridian groups compared with the model group (P < 0.05). The promoting effect of electro-acupuncture at Ren and Du meridians on ERK1/2 phosphorylation was superior to electro-acupuncture at the Du meridian alone on day 14 after model induction (P < 0.05). However,PD98059 completely abolished the promoting effect of electro-acupuncture at Ren/Du meridians on pERK1/2 expression (P < 0.05). CONCLUSION:Electro-acupuncture at Ren and Du meridians increased proliferation of subventricular zone neural stem cells,which was related to activation of the ERK pathway in a rat model of cerebral ischemia injury.展开更多
Many studies have shown that fibronectin type III domain-containing protein 5(FDNC5) and brain-derived neurotrophic factor(BDNF) play vital roles in plasticity after brain injury. An enriched environment refers to an ...Many studies have shown that fibronectin type III domain-containing protein 5(FDNC5) and brain-derived neurotrophic factor(BDNF) play vital roles in plasticity after brain injury. An enriched environment refers to an environment that provides animals with multi-sensory stimulation and movement opportunities. An enriched environment has been shown to promote the regeneration of nerve cells, synapses, and blood vessels in the animal brain after cerebral ischemia;however, the exact mechanisms have not been clarified. This study aimed to determine whether an enriched environment could improve neurobehavioral functions after the experimental inducement of cerebral ischemia and whether neurobehavioral outcomes were associated with the expression of FDNC5 and BDNF. This study established ischemic mouse models using permanent middle cerebral artery occlusion(pMCAO) on the left side. On postoperative day 1, the mice were randomly assigned to either enriched environment or standard housing condition groups. Mice in the standard housing condition group were housed and fed under standard conditions. Mice in the enriched environment group were housed in a large cage, containing various toys, and fed with a standard diet. Sham-operated mice received the same procedure, but without artery occlusion, and were housed and fed under standard conditions. On postoperative days 7 and 14, a beam-walking test was used to assess coordination, balance, and spatial learning. On postoperative days 16–20, a Morris water maze test was used to assess spatial learning and memory. On postoperative day 15, the expression levels of FDNC5 and BDNF proteins in the ipsilateral cerebral cortex were analyzed by western blot assay. The results showed that compared with the standard housing condition group, the motor balance and coordination functions(based on beam-walking test scores 7 and 14 days after operation), spatial learning abilities(based on the spatial learning scores from the Morris water maze test 16–19 days after operation), and memory abilities(based on the memory scores of the Morris water maze test 20 days after operation) of the enriched environment group improved significantly. In addition, the expression levels of FDNC5 and BDNF proteins in the ipsilateral cerebral cortex increased in the enriched environment group compared with those in the standard housing condition group. Furthermore, the Pearson correlation coefficient showed that neurobehavioral functions were positively associated with the expression levels of FDNC5 and BDNF(r = 0.587 and r = 0.840, respectively). These findings suggest that an enriched environment upregulates FDNC5 protein expression in the ipsilateral cerebral cortex after cerebral ischemia, which then activates BDNF protein expression, improving neurological function. BDNF protein expression was positively correlated with improved neurological function. The experimental protocols were approved by the Institutional Animal Care and Use Committee of Fudan University, China(approval Nos. 20160858 A232, 20160860 A234) on February 24, 2016.展开更多
Acute focal cerebral ischemic stroke(IS)is a leading cause of morbidity and mortality worldwide.Acupuncture is an emerging alternative therapy that has been beneficial to acute brain ischemia.However,the underlying pr...Acute focal cerebral ischemic stroke(IS)is a leading cause of morbidity and mortality worldwide.Acupuncture is an emerging alternative therapy that has been beneficial to acute brain ischemia.However,the underlying protective mechanism of its neuroprotective effect remains unclear.Human original circadian rhythm will be lost after IS,which seriously affects the quality of life and functional recovery of stroke patients.We hypothesize that acupuncture treats IS by regulating the balance of Clock and Bmal1.This study aims to explore the effect of acupuncture at acupoints GV20 and BL23 on neuroprotection and anti-apoptosis in middle cerebral artery occlusion(MCAO)rats and expression of apoptosis and circadian rhythm related proteins.Male Sprague-Dawley(SD)rats were randomly divided into five groups:normal group(Normal),sham model group(Sham MCAO),MCAO model group(MCAO),sham electroacupuncture group(Sham EA)and electroacupuncture group(EA).The MCAO model was prepared by electrocoagulation.The first acupuncture treatment was performed within 2 h after surgery,and then acupuncture therapy was performed on 1st day,2nd day and 3rd day respectively.After their neurological examination at 72 h of ischemia,the rats from each group were sacrificed.Triphenyltetrazolium chloride(TTC)staining was used to evaluate the brain infarct size.Ultrastructural observation on cerebral ischemic cortex and serum inflammatory cytokines were evaluated.TUNEL staining was used to detect cell apoptosis of brain tissue.The expression levels of proteins Bax,bcl-2,caspase-3,Clock and Bmal1 in the cerebral ischemic region were detected by immunofluorescence staining.Here,we presented evidence that EA at GV20 and BL23 could significantly improve the neurological deficit score and infarct size,and alleviate the cell apoptosis of brain tissue.Moreover,acupuncture treatment upregulated the anti-apoptotic Bcl-2/Bax ratio and reversed the upregulation of caspase-3 following 72-h cerebral ischemia.In addition,the expression levels of circadian proteins Clock and Bmal1 were upregulated in EA group while compared with MCAO group.Our study demonstrated that acupuncture exerted neuroprotective effect against neuronal apoptosis after stroke and the mechanism might be related with regulation of circadian rhythm proteins Clock and Bmal1.展开更多
文摘Objective:To understand the clinical characteristics of patients with embryonic posterior cerebral artery and its correlation with abnormal vascular development.Methods:The clinical data of 396 patients with embryonic posterior cerebral artery confirmed by magnetic resonance angiography(MRA)and computed tomography angiography(CTA)were analyzed.Results:Two-hundred patients had clinical manifestations of posterior circulation ischemia,including recurrent dizziness,vertigo,and tinnitus;45 had headaches,97 had limb weakness,and 16 patients had syncope or impaired consciousness.Seventy-six patients with circulatory infarction were admitted to the hospital.There were 251 patients with history of hypertension,74 with diabetes,113 with hyperlipidemia,13 with dominant vertebral artery,10 with intracranial aneurysm,and 19 with absence of A1 segment of the anterior cerebral artery(considering developmental variation).Conclusion:Embryonic posterior cerebral artery develops abnormally during the embryonic period,often accompanied by abnormal vascular access.Due to abnormal hemodynamics,the incidence of posterior circulation ischemia,aneurysm,and infarction increases in such patients.
基金supported by the National Natural Science Foundation of China,No.81371521
文摘Fluid-attenuated inversion recovery(FLAIR) vascular hyperintensity(FVH) is used to assess leptomeningeal collateral circulation, but clinical outcomes of patients with FVH can be very different. The aim of the present study was to assess a FVH score and explore its relationship with clinical outcomes. Patients with acute ischemic stroke due to middle cerebral artery M1 occlusion underwent magnetic resonance imaging and were followed up at 10 days(National Institutes of Health Stroke Scale) and 90 days(modified Rankin Scale) to determine short-term clinical outcomes. Effective collateral circulation indirectly improved recovery of neurological function and short-term clinical outcome by extending the size of the pial penumbra and reducing infarct lesions. FVH score showed no correlation with 90-day functional clinical outcome and was not sufficient as an independent predictor of short-term clinical outcome.
基金The authors thank Beijing University of Chinese Medicine for providing the necessary facilities and funding this project(No.2180071720034).
文摘Objective:Longshengzhi capsule(LSZC)is an optimized preparation based on the traditional Chinese Medicine formula Buyanghuanwu Decoction(BYHWD),and is approved by the China Food and Drug Administration for treating stroke-induced disability and vascular diseases.Herein,we examined the pharmacodynamics,anti-apoptotic and anti-oxidant actions,and potential mechanisms of action of LSZC following stroke in rats.Methods:Permanent middle cerebral artery occlusion(MCAO)was used as an ischemic stroke model.LSZC was administered intragastrically.We examined the survival rate,bodyweight,and neurological deficits in stroke rats.Brain infarct size was determined by 2,3,5-triphenyltetrazolium chloride staining.Brain pathology was examined using hematoxylin and eosin staining,Nissl staining,and TdT-mediated dUTP Nick-End Labeling staining.Malondialdehyde,catalase,superoxide dismutase,and glutathione levels were examined by commercial kits.Expression of Nrf2,heme oxygenase-1,Bax,Bcl-2,cleaved caspase-3,and caspase-3 proteins in brain tissue was measured by Western blot.Results:LSZC markedly improved the survival rate and bodyweight,and reduced infarct volume and neurological deficit scores,in MCAO stroke rats.LSZC also significantly attenuated oxidative stress,as indicated by decreased expression of malondialdehyde,and upregulation of Nrf2,heme oxygenase-1,catalase,superoxide dismutase,and glutathione.Moreover,LSZC significantly decreased apoptosis,including a decrease in Bax and cleaved caspase-3 expression,and an increase in Bcl-2,as well as a reduction in numbers of apoptotic neurons.Conclusion:LSZC treatment is neuroprotective against ischemic stroke,potentially via reducing oxidative stress and apoptosis.The Nrf2 and apoptotic signaling pathways may play important roles in the antioxidant and anti-apoptotic actions of LSZC.
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 key project of the Natural Science Foundation of Hubei Province of China(No.ZRZ2014000254)the National Natural Science Foundation of China(No.81571146)
文摘The histopathological features of the middle cerebral artery(MCA) and superficial temporal artery(STA) from moyamoya disease(MMD) and their relationships with gender,age,angiography stage were explored.The causes and the clinical significance of vasculopathy of STA were also discussed.The clinical data and specimens of MCA and STA from 30 MMD patients were collected.Twelve samples of MCA and STA from non-MMD patients served as control group.Histopathological examination was then performed by measuring the thickness of intima and media,and statistical analysis was conducted.The MCA and STA specimens from MMD group had apparently thicker intima and thinner media than those from the control group.There was no significant pathological difference between the hemorrhage group and non-hemorrhage group,and between the males and females in MMD patients.Neither the age nor the digital subtraction angiography(DSA) stage was correlated with the thickness of intima in MCA and STA.MMD is a systemic vascular disease involving both intracranial and extracranial vessels.Preoperative external carotid arteriography,especially super-selective arteriography of the STA,benefits the selection of donor vessel.
基金Supported by National Natural Science Foundation of China,No.32070791the Key Scientific Research Projects of Military Logistics,No.BWJ20J002.
文摘BACKGROUND Aneurysm compression,diabetes,and traumatic brain injury are well-known causative factors of oculomotor nerve palsy(ONP),while cases of ONP induced by neurovascular conflicts have rarely been reported in the medical community.Here,we report a typical case of ONP caused by right posterior cerebral artery(PCA)compression to increase neurosurgeons’awareness of the disease and reduce misdiagnosis and recurrence.CASE SUMMARY A 54-year-old man without a known medical history presented with right ONP for the past 5 years.The patient presented to the hospital with right ptosis,diplopia,anisocoria(rt 5 mm,lt 2.5 mm),loss of duction in all directions,abduction,and light impaired pupillary reflexes.Magnetic resonance angiography and computed tomography venography examinations showed no phlebangioma,aneurysm,or intracranial lesion.After conducting oral glucose tolerance and prostigmin tests,diabetes and myasthenia gravis were excluded.Cranial nerve magnetic resonance imaging showed that the right PCA loop was in direct contact with the cisternal segment of the right oculomotor nerve(ON).Microvascular decompression(MVD)of the culprit vessel from the ON through a right subtemporal craniotomy was carried out,and the ONP symptoms were significantly relieved after 3 mo.CONCLUSION Vascular compression of the ON is a rare pathogeny of ONP that may be refractory to drug therapy and ophthalmic strabismus surgery.MVD is an effective treatment for ONP induced by neurovascular compression.
基金the Natural Science Foundation of Shandong Province, No. Y2004C04
文摘BACKGROUND: Insulin-like growth factor-I(IGF-1), as one of the important members of growth factor family, participants in the regulation of many physiological functions and behaviors, having very strong neuroprotective effect. However, the expression of IGF-1 following cerebral ischemia/reperfusion is still disputed. OBJECTIVE: To observe the expression of IGF-1 and protein of corpora striata in ischemic side at the early stage of middle cerebral artery ischemia/reperfusion in rhesus monkey. DESIGN: A completely randomized grouping design, controlled animal experiment. SETTING: Institute of Cerebrovascular Disease, Affiliated Hospital of Medical College of Qingdao University. MATERIALS: ① Totally 17 rhesus monkeys , of either gender, aged 4 to 5 years, were enrolled . Seven rhesus monkeys observed with gene chip were randomly divided into 2 groups: sham operation group (n=3) and ischemia/reperfusion group (n=4). Ten rhesus monkeys observed with in situ hybridization and immunohistochemistry method were randomly divided into 2 groups: sham operation group (n=3)and ischemia/reperfusion group (n=7). Rhesus monkeys observed under microscope were divided into 2 groups: sham operation group (n=6) and ischamia/reperfusion group (n=11). ② Materials used in the experiment: cresyl violet (Sigma Company, America); immunohistochemical reagent kit ( Huamei Bio-engineering Company); In situ hybridization reagent kit (Boshide Bio-engineering Co.Ltd, Wuhan); 12 800 dots chip (Boxing Company, Shanghai). METHODS: This experiment was carried out at the Institute of Cerebrovascular Disease, Affiliated Hospital of Medical College of Qingdao University from January 2001 to December 2003. ① The onset area of middle cerebral artery was blocked for 2 hours, middle cerebral artery ischemia/reperfusion models were created. ② After ischemia/reperfusion for 24 hours, cerebral tissue sections of rhesus monkeys were prepared and stained with cresyl violet. Image analysis was performed with 500IW image analysis software. Morphological change of corpora striata of operative side was observed in the rhesus monkeys between two groups. Total RNA was extracted from cerebral tissue. ③ Detection of gene chip: Cy3-duTP and Cy5-duTP were used to respectively perform reverse transcription labeling. The sample was reversely transcribed into cDNA, then hybridized with cDNA of cerebral tissue. Genes with the separate absolute value of cy3 and cy5>800, cy3/cy5 > 2(high expression) or < 0.5 (low expression) were found out. Those were genes with differential expression. ④ The expressions of IGF-1 mRNA and protein level of corpora striata in ischemic side of rhesus monkeys were detected between sham operation group and ischemia/reperfusion group at 9 and 24 hours after ischemia/reperfusion with in situ hybridization method and immunohistochemical method. Brown granules were IGF-1 protein positive cells. ⑤ Analysis of variance was used in the difference comparison of measurement data among groups. MAIN OUTCOME MEASURES: ① Change of morphological structure of corpora striata at ischemic side in rhesus monkeys. ② Change of cerebral gene expression profiles at ischemia/reperfusion in rhesus monkeys between two groups. ③ Expression of IGF-1 mRNA and protein level of corpora striata at ischemia/reperfusion in rhesus monkeys between two groups. RESULTS: ① Pathological change : Obvious pathological change of cerebral infarction appeared in the ischemia and reperfusion group, while there was no such pathological change in the sham operation group. ② Change of gene expression profile : There were 4480 genes with difference expression in the ischemia/reperfusion group and sham-operation group, in which, 260 genes had high expression and their absolute value was over 800, and 63 genes had low expression. cy3/cy5 of IGF-1 was 0.379, being relative low expression. ③ IGF-1 mRNA and protein positive cell counts in corpora striata at cerebral ischemic side[IGF-1 mRNA:(9.72±1.18),(9.11±0.76),(14.77±0.60) counts/field;IGF-1 protein:(15.11±1.83),(15.39±0.78),(34.62±0.97)counts/field,P < 0.05-0.01]. CONCLUSION: IGF-1 mRNA and protein are lowly expressed in middle cerebral artery of rhesus monkeys at ischemia/reperfusion.
基金The project supported by Hunan province Science and Technology Plan Projects of China(2015DK3010)
文摘OBJECTIVE To study the role of Ginkgo biloba extract-761(EGb-761)in the recovery of gait abnormality and its neuroprotective effect against the brain injury induced by permanent middle cerebral artery occlu-sion in rats.METHODS Male Sprague Dawley rats(n=200,240-305 g)were anesthetized with 0.2%pentobarbital sodium diluted in physiological saline(2.0 m L·kg-1,ip).Then a monofilament coated with poly-L-lysine,was used to occlude the origin of the middle cerebral artery.It was inserted into the internal carotid artery lumen until it met mild resistance,approximately 20mm beyond the common carotid artery bifurcation.The suture was secured with a ligature and maintained in place until sacrifice.The same surgical procedure was conducted in sham-operated rats in which the middle cerebral artery was not occluded.Motor and behavioral changes were assessed after surgery using a five point scale.The rats securing the point scale above 2 were included in the study.The rats were randomly divided into control,and treated groups:EGb-761(20,50,and 100 mg·kg-1).The treated groups were oral y administered(10 mL·kg-1)for 28 d.On 7th,14th,21st,and 28th day the neurological scores,rotar rod test and gait assessment(the automated computer-assisted method)were performed.The brains were collected for TTC staining and histopathological analysis.RESULTS 1)Weight:On 28th day,EGb-761(20 mg·kg-1,)significantly increased the weight of the rat by^8%as compared to control(~300 g).However,at 50 mg·kg-1,and 100 mg·kg-1,a significant increase of^7-7.6%(control:~232 g),and^7.3-7%,respectively from 14 to 28 days was noted.2)Neurological scores:On 28thday,EGb-761(20,50,and 100 mg·kg-1)significantly decreased the neurological scores by^18%,~22%,~21%,respectively as compared to control(~2.07).3)Rotar rod test:On 28thday,EGb-761(50,and100 mg·kg-1)significantly increased by^69.1%,~74.1%,respectively as compared to control(~28.2).4)Gait assessment:On 7th,14th,21st,and 28thday,EGb-761(20,50,and 100 m·kg-1)significantly reduced the average body angle,on 7th,14th,21st,and 28thday,EGb-761(100 mg·kg-1)significantly increased the walk speed and reduced the average walking cycle,EGb-761(50,and 100 mg·kg-1)significantly the area of the left brain/right brain area percentage and reduced tissue pathologic neuron injury.CONCLUSION Ginkgo biloba extract EGb-761 has obvious improve behavior disorders,and has a protective neuroprotective effect against the brain injury induced by permanent middle cerebral artery occlusion.
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 National Natural Science Foundation of China,No.82101567Doctoral Start-up Foundation of Liaoning Province,No.2021-BS-111345 Talent Project of Shengjing Hospital of China Medical University,No.M0673(all to XYF)。
文摘Cerebral ischemia/reperfusion injury impairs learning and memory in patients.Studies have shown that synaptic function is involved in the formation and development of memory,and that DNA methylation plays a key role in the regulation of learning and memory.To investigate the role of DNA hypomethylation in cerebral ischemia/reperfusion injury,in this study,we established a rat model of cerebral ischemia/reperfusion injury by occlusion of the middle cerebral artery and then treated the rats with intraperitoneal 5-aza-2′-deoxycytidine,an inhibitor of DNA methylation.Our results showed that 5-aza-2′-deoxycytidine markedly improved the neurological function,and cognitive,social and spatial memory abilities,and dose-dependently increased the synaptic density and the expression of SYP and SHANK2 proteins in the hippocampus in a dose-dependent manner in rats with cerebral ischemia/reperfusion injury.The effects of 5-aza-2′-deoxycytidine were closely related to its reduction of genomic DNA methylation and DNA methylation at specific sites of the Syp and Shank2 genes in rats with cerebral ischemia/reperfusion injury.These findings suggest that inhibition of DNA methylation by 5-aza-2′-deoxycytidine promotes the recovery of learning and memory impairment in a rat model of cerebral ischemia/reperfusion injury.These results provide theoretical evidence for stroke treatment using epigenetic methods.
文摘A 51-year-old man presented with subarachnoid haemorrhage with mild hydrocephaly. Digital substraction angiography and 3-D Computerised Angiogram (CT) revealed a saccular aneurysm at bifurcation of azygos anterior cerebral artery (ACA) and other vascular variations such as vertebral artery fenestration and hypoplasia in one anterior cerebral artery. We performed aneurysmal neck clipping with good outcome and postoperative 3-D CT angiogram showed complet obliteration of aneurysm. Although azygos arteries are rare in healthy population, aneurysms of azygos ASA are not rare due to increased haemodynamic stress. We wanted to point out to better visualisation of anatomical variations at 3-D CT angiogram comparing DSA in patients with intracranial aneurysm.
基金Clinical Study of Endovascular Treatment of Severe Middle Cerebral Artery Stenosis or Occlusion and Vascular Cognitive Impairment.Project No.:2019zc184。
文摘It is very important to study the factors affecting the incidence,progress and prognosis of patients with vascular dementia.50 cases of severe middle cerebral artery stenosis or occlusion underwent endovascular treatment(25 cases of mild cognitive dysfunction,25 cases of moderate cognitive dysfunction)were divided into two groups,where a medical drug treatment group and a control group established with 25 cases in each group.The cognitive function of each group of patients was evaluated before operation,7 days after operation,30 days after operation,and 180 days after operation.CTP was used to compare the hemodynamic changes in patients before and after operation.The severe stenosis or occlusion of the middle cerebral artery in patients can be improved,and the intracranial blood supply of patients with poorly compensated medial cranial circulation and hypoperfusion can be restored to a certain extent.Meanwhile,improvement of cognitive function was definitive in some patients with cognitive dysfunction.To guide the formulation of treatment plans for patients with severe middle cerebral artery stenosis or occlusion.
文摘Objective To report the clinical diagnosis and microsurgical treatment of ruptured distal anterior cerebral artery aneurysm (DACAA) patients treated over the last 3 years. Methods 9 consecutive cases of ruptured DACAA operated from October 2007 to March 2010 were reviewed and followed up. Results 11 aneurysms were clipped
基金supported by the National Natural Science Foundation of China,Nos.81672261(to XH),81972151(to HZ),82372568(to JL)the Natural Science Foundation of Guangdong Province,Nos.2019A1515011106(to HZ),2023A1515030080(to JL)。
文摘Prolife ration of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage.Transcranial magnetic stimulation(TMS)has recently emerged as a tool for inducing endogenous neural stem cell regeneration,but its underlying mechanisms remain unclea r In this study,we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem cells.Additionally,repetitive TMS reduced the volume of cerebral infa rction in a rat model of ischemic stro ke caused by middle cerebral artery occlusion,im p roved rat cognitive function,and promoted the proliferation of neural stem cells in the ischemic penumbra.RNA-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ischemia.Furthermore,PCR analysis revealed that repetitive TMS promoted AKT phosphorylation,leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and Cdk4.This effect was also associated with activation of the glycogen synthase kinase 3β/β-catenin signaling pathway,which ultimately promotes the prolife ration of neural stem cells.Subsequently,we validated the effect of repetitive TMS on AKT phosphorylation.We found that repetitive TMS promoted Ca2+influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway,thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3β/β-catenin pathway.These findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+influx-dependent phosphorylated AKT/glycogen synthase kinase 3β/β-catenin signaling pathway.This study has produced pioneering res ults on the intrinsic mechanism of repetitive TMS to promote neural function recove ry after ischemic stro ke.These results provide a stro ng scientific foundation for the clinical application of repetitive TMS.Moreover,repetitive TMS treatment may not only be an efficient and potential approach to support neurogenesis for further therapeutic applications,but also provide an effective platform for the expansion of neural stem cells.
基金supported by the National Natural Science Foundation of China,Nos.81772134(to KX),81971891(to KX),82172196(to KX),81571939(to KX)the Fundamental Research Funds for the Central Universities of Central South University of China,No.2020zzts218,(to WTY)Hunan Provincial Innovation Foundation For Postgraduate of China,Nos.CX20200116(to WTY),CX20190139(to LSL).
文摘Some scholars have recently developed the concept of PANoptosis in the study of infectious diseases where pyroptosis,apoptosis and necroptosis act in consort in a multimeric protein complex,PANoptosome.This allows all the components of PANoptosis to be regulated simultaneously.PANoptosis provides a new way to study the regulation of cell death,in that different types of cell death may be regulated at the same time.To test whether PANoptosis exists in diseases other than infectious diseases,we chose cerebral ischemia/reperfusion injury as the research model,collected articles researching cerebral ischemia/reperfusion from three major databases,obtained the original research data from these articles by bibliometrics,data mining and other methods,then integrated and analyzed these data.We selected papers that investigated at least two of the components of PANoptosis to check its occurrence in ischemia/reperfusion.In the cell model simulating ischemic brain injury,pyroptosis,apoptosis and necroptosis occur together and this phenomenon exists widely in different passage cell lines or primary neurons.Pyroptosis,apoptosis and necroptosis also occurred in rat and mouse models of ischemia/reperfusion injury.This confirms that PANoptosis is observed in ischemic brain injury and indicates that PANoptosis can be a target in the regulation of various central nervous system diseases.
基金the National Natural Science Foundation of China,No.30371808the Natural Science Foundation of Guangdong Province,No.5009688
文摘BACKGROUND:Studies have shown that electro-acupuncture at the Ren meridian could improve proliferation of subventricular zone neural stem cells in cerebral-ischemic rats. However,there are few reports on the influence of electro-acupuncture at the Du meridian on neural stem cell proliferation. OBJECTIVE:To observe the influence of electro-acupuncture at Ren and Du meridians on neural stem cell proliferation in the subventricular zone and altered signal transduction in cerebral ischemia rats. DESIGN,TIME AND SETTING:A randomized,controlled,animal experiment was performed at the Laboratory of Human Anatomy,Medical College of Sun Yat-sen University from May 2006 to February 2008. MATERIALS:Mouse anti-rat bromodeoxyuridine (BrdU) monoclonal antibody was provided by Sigma,USA; mouse anti-rat nestin monoclonal antibody and extracellular signal-regulated protein kinase (ERK) specific inhibitor PD98059 were provided by Calbiochem,Germany; acupuncture needle was provided by Suzhou Acupuncture Supplies,China. METHODS:A total of 126 rats were randomly assigned to four groups:model (n = 36),Du meridian (n = 36),Ren/Du meridian (n = 36),and Ren/Du meridian + PD98059 (n = 18). Rats in the Ren /Du meridian + PD98059 group were observed on days 7 (n = 6) and 14 (n = 12) after cerebral ischemia injury. Rats in the model,Du meridian,and Ren/Du meridian groups were observed on days 7,14,and 28 after cerebral ischemia injury,with 12 rats per group at each time point. Thread occlusion was used to establish middle cerebral artery occlusion models. Electro-acupuncture was performed at Renzhong (DU 26) and Baihui (DU 20) acupoints in the Du meridian group,as well as Chengjiang (RN 24),Guanyuan (RN 4),Renzhong,and Baihui acupoints in the Ren/Du meridian and Ren/Du meridian + PD98059 groups 2 days after model establishment. In addition,electro-acupuncture stimulation with disperse-dense waves was performed,with 30 Hz disperse wave,100 Hz dense wave,and 5 V intensity for 20 minutes. Rats in the Ren/Du meridian + PD98059 group were treated with 0.2 μg PD98059 injection into the subventricular zone,2 μL per rat. Rats in the model group were not treated with electro-acupuncture. MAIN OUTCOME MEASURES:BrdU/nestin immunofluorescent staining was used to detect proliferating neural stem cells in the subventricular zone of cerebral ischemia rats; Western blot was used to determine phosphorylated ERK1 and 2 (pERK1/2) expression in the subventricular zone. RESULTS:On days 14 and 28 after cerebral ischemia,there were significantly more BrdU-positive and BrdU/nestin-positive cells in the Ren /Du meridian group compared with the Du meridian group (P < 0.05). PD98059 decreased the number of BrdU-positive and BrdU/nestin-positive cells induced by electro-acupuncture at the Ren and Du meridians (P < 0.05). On days 7,14,and 28 after treatment,pERK1/2 expression was significantly greater in the Du meridian and Ren/Du meridian groups compared with the model group (P < 0.05). The promoting effect of electro-acupuncture at Ren and Du meridians on ERK1/2 phosphorylation was superior to electro-acupuncture at the Du meridian alone on day 14 after model induction (P < 0.05). However,PD98059 completely abolished the promoting effect of electro-acupuncture at Ren/Du meridians on pERK1/2 expression (P < 0.05). CONCLUSION:Electro-acupuncture at Ren and Du meridians increased proliferation of subventricular zone neural stem cells,which was related to activation of the ERK pathway in a rat model of cerebral ischemia injury.
基金supported by the National Natural Science Foundation of China,Nos.81601961(to KWY),81672242(to YW)the Key Construction Projects of Shanghai Health and Family Planning on Weak Discipline,China,No.2015ZB0401(to YW)
文摘Many studies have shown that fibronectin type III domain-containing protein 5(FDNC5) and brain-derived neurotrophic factor(BDNF) play vital roles in plasticity after brain injury. An enriched environment refers to an environment that provides animals with multi-sensory stimulation and movement opportunities. An enriched environment has been shown to promote the regeneration of nerve cells, synapses, and blood vessels in the animal brain after cerebral ischemia;however, the exact mechanisms have not been clarified. This study aimed to determine whether an enriched environment could improve neurobehavioral functions after the experimental inducement of cerebral ischemia and whether neurobehavioral outcomes were associated with the expression of FDNC5 and BDNF. This study established ischemic mouse models using permanent middle cerebral artery occlusion(pMCAO) on the left side. On postoperative day 1, the mice were randomly assigned to either enriched environment or standard housing condition groups. Mice in the standard housing condition group were housed and fed under standard conditions. Mice in the enriched environment group were housed in a large cage, containing various toys, and fed with a standard diet. Sham-operated mice received the same procedure, but without artery occlusion, and were housed and fed under standard conditions. On postoperative days 7 and 14, a beam-walking test was used to assess coordination, balance, and spatial learning. On postoperative days 16–20, a Morris water maze test was used to assess spatial learning and memory. On postoperative day 15, the expression levels of FDNC5 and BDNF proteins in the ipsilateral cerebral cortex were analyzed by western blot assay. The results showed that compared with the standard housing condition group, the motor balance and coordination functions(based on beam-walking test scores 7 and 14 days after operation), spatial learning abilities(based on the spatial learning scores from the Morris water maze test 16–19 days after operation), and memory abilities(based on the memory scores of the Morris water maze test 20 days after operation) of the enriched environment group improved significantly. In addition, the expression levels of FDNC5 and BDNF proteins in the ipsilateral cerebral cortex increased in the enriched environment group compared with those in the standard housing condition group. Furthermore, the Pearson correlation coefficient showed that neurobehavioral functions were positively associated with the expression levels of FDNC5 and BDNF(r = 0.587 and r = 0.840, respectively). These findings suggest that an enriched environment upregulates FDNC5 protein expression in the ipsilateral cerebral cortex after cerebral ischemia, which then activates BDNF protein expression, improving neurological function. BDNF protein expression was positively correlated with improved neurological function. The experimental protocols were approved by the Institutional Animal Care and Use Committee of Fudan University, China(approval Nos. 20160858 A232, 20160860 A234) on February 24, 2016.
基金This study was supported by the Foundation of Hubei Provincal Department of Education of China(No.B2018098).
文摘Acute focal cerebral ischemic stroke(IS)is a leading cause of morbidity and mortality worldwide.Acupuncture is an emerging alternative therapy that has been beneficial to acute brain ischemia.However,the underlying protective mechanism of its neuroprotective effect remains unclear.Human original circadian rhythm will be lost after IS,which seriously affects the quality of life and functional recovery of stroke patients.We hypothesize that acupuncture treats IS by regulating the balance of Clock and Bmal1.This study aims to explore the effect of acupuncture at acupoints GV20 and BL23 on neuroprotection and anti-apoptosis in middle cerebral artery occlusion(MCAO)rats and expression of apoptosis and circadian rhythm related proteins.Male Sprague-Dawley(SD)rats were randomly divided into five groups:normal group(Normal),sham model group(Sham MCAO),MCAO model group(MCAO),sham electroacupuncture group(Sham EA)and electroacupuncture group(EA).The MCAO model was prepared by electrocoagulation.The first acupuncture treatment was performed within 2 h after surgery,and then acupuncture therapy was performed on 1st day,2nd day and 3rd day respectively.After their neurological examination at 72 h of ischemia,the rats from each group were sacrificed.Triphenyltetrazolium chloride(TTC)staining was used to evaluate the brain infarct size.Ultrastructural observation on cerebral ischemic cortex and serum inflammatory cytokines were evaluated.TUNEL staining was used to detect cell apoptosis of brain tissue.The expression levels of proteins Bax,bcl-2,caspase-3,Clock and Bmal1 in the cerebral ischemic region were detected by immunofluorescence staining.Here,we presented evidence that EA at GV20 and BL23 could significantly improve the neurological deficit score and infarct size,and alleviate the cell apoptosis of brain tissue.Moreover,acupuncture treatment upregulated the anti-apoptotic Bcl-2/Bax ratio and reversed the upregulation of caspase-3 following 72-h cerebral ischemia.In addition,the expression levels of circadian proteins Clock and Bmal1 were upregulated in EA group while compared with MCAO group.Our study demonstrated that acupuncture exerted neuroprotective effect against neuronal apoptosis after stroke and the mechanism might be related with regulation of circadian rhythm proteins Clock and Bmal1.
