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Post-Acute ischemic stroke hyperglycemia aggravates destruction of the blood-brain barrier

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Neural Regeneration Research 2024年第6期19卷 1344-1350页

作者： Tianqi Xu Jianhong Yang Yao Xu Xiaofeng Wang Xiang Gao Jie Sun Chenhui Zhou Yi Huang Department of Neurology The First Affiliated Hospital of Ningbo University Department of General Surgery The First Affiliated Hospital of Ningbo University Department of Neurosurgery The First Affiliated Hospital of Ningbo University Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province

Post-Acute ischemic stroke hyperglycemia increases the risk of hemorrhagic transformation, which is associated with blood-brain barrier disruption. Brain microvascular endothelial cells are a major component of the blood-brain barrier. Intercellular mitochondrial transfer has emerged as a novel paradigm for repairing cells with mitochondrial dysfunction. In this study, we first investigated whether mitochondrial transfer exists between brain microvascular endothelial cells, and then investigated the effects of post-Acute ischemic stroke hyperglycemia on mitochondrial transfer between brain microvascular endothelial cells. We found that healthy brain microvascular endothelial cells can transfer intact mitochondria to oxygen glucose deprivation-injured brain microvascular endothelial cells. However, post-oxygen glucose deprivation hyperglycemia hindered mitochondrial transfer and exacerbated mitochondrial dysfunction. We established an in vitro brain microvascular endothelial cell model of the blood-brain barrier. We found that post-Acute ischemic stroke hyperglycemia reduced the overall energy metabolism levels of brain microvascular endothelial cells and increased permeability of the blood-brain barrier. In a clinical study, we retrospectively analyzed the relationship between post-Acute ischemic stroke hyperglycemia and the severity of hemorrhagic transformation. We found that post-Acute ischemic stroke hyperglycemia serves as an independent predictor of severe hemorrhagic transformation. These findings suggest that post-Acute ischemic stroke hyperglycemia can aggravate disruption of the blood-brain barrier by inhibiting mitochondrial transfer.

关键词： Acute ischemic stroke blood-brain barrier brain microvascular endothelial cells mitochondrial transfer stress hyperglycemia

Non-coding RNAs in Acute ischemic stroke:from brain to periphery

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Neural Regeneration Research 2025年第1期20卷 116-129页

作者： Shuo Li Zhaohan Xu Shiyao Zhang Huiling Sun Xiaodan Qin Lin Zhu Teng Jiang Junshan Zhou Fuling Yan Qiwen Deng Department of Neurology Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu ProvinceChina Department of Neurology Zhongda HospitalSchool of MedicineSoutheast UniversityNanjingJiangsu ProvinceChina General Clinical Research Center Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu ProvinceChina

Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and disability.Accurate predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for Acute ischemic stroke remain undetermined.With innovations in high-throughput gene sequencing analysis,many aberrantly expressed non-coding RNAs(ncRNAs)in the brain and peripheral blood after Acute ischemic stroke have been found in clinical samples and experimental models.Differentially expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes,leading to neuroprotection or deterioration,thus ncRNAs can serve as therapeutic targets in Acute ischemic stroke.Moreover,distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for Acute ischemic stroke prediction,diagnosis,and prognosis.In particular,ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after Acute ischemic stroke.In this review,we consolidate the latest progress of research into the roles of ncRNAs(microRNAs,long ncRNAs,and circular RNAs)in the pathological processes of Acute ischemic stroke–induced brain damage,as well as the potential of these ncRNAs to act as biomarkers for Acute ischemic stroke prediction,diagnosis,and prognosis.Findings from this review will provide novel ideas for the clinical application of ncRNAs in Acute ischemic stroke.

关键词： Acute ischemic stroke apoptosis blood–brain barrier damage circular RNAs excitatory toxicity long non-coding RNAs microRNAs neuroinflammation non-coding RNAs oxidative stress

Intravenous thrombolysis for Acute ischemic stroke with extended time window

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Chinese Medical Journal 2021年第22期134卷 2666-2674页

作者： Xue Jia Wen Wang Bo Wu Xin Sun Chinese Evidence-based Medicine Center West China School of MedicineWest China HospitalSichuan UniversityChengduSichuan 610041China Department of Postgraduate West China School of MedicineWest China HospitalSichuan UniversityChengduSichuan 610041China Department of Neurology West China School of MedicineWest China HospitalSichuan UniversityChengduSichuan 610041China.

Background:Intravenous thrombolysis(IVT)is an effective way for treating Acute ischemic stroke(AIS).However,its effects have not been established among AIS patients with unclear stroke symptoms or with stroke onset for>4.5 h.Methods:We searched PubMed,Embase,Web of Science,Cochrane Central Register of Controlled Trials and Google Scholar databases for randomized controlled trials that compared IVT(IVT group)and placebo or usual care(control group[CG])in AIS patients with disease onset for>4.5 h.The outcomes of interest included the favorable functional outcome(defined as modified Rankin Scale[mRS]scores 0–1)at 90 days,the functional independence(defined as mRS scores 0–2)at 90 days,proportion of patients with symptomatic intracerebral hemorrhage(sICH)and death at 90 days.We assessed the risk of bias using the Cochrane tool.Pre-specified subgroup analyses were performed by age(70 years or>70 years),National Institute of Health stroke Scale(NIHSS,10 or>10)and time window(4.5–9.0 h or>9.0 h).Results:Four trials involving 848 patients were eligible.The risk of bias of included trials was low.Patients in the IVT group were more likely to achieve favorable functional outcomes(45.8%vs.36.7%;OR 1.48,95%CI 1.12–1.96)and functional independence(63.8%vs.55.7%;OR 1.43,95%CI 1.08–1.90)at 90 days,but had higher risk of sICH(3.0%vs.0.5%;OR 5.28,95%CI 1.35–20.68)at 90 days than those in the CG.No significant difference in death at 90 days was found between the two groups(7.0%vs.4.1%;OR 1.80;95%CI 0.97–3.34).Conclusions:Use of IVT in patients with extended time window may improve their functional outcomes at 90 days,although IVT may induce increased risk of sICH.Care of these patients should well balance the potential benefits and harms of IVT.

关键词： Intravenous thrombolysis Acute ischemic stroke Time window Meta-analysis

Proteomic investigations of Acute ischemic stroke in animal models:a narrative review

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Journal of Bio-X Research 2023年第1期6卷 15-22页

作者： Fangxu Sun Rong-Fang Gu Ru Wei Chemical Biology and Proteomics BiogenCambridgeMAUSA

Acute ischemic stroke(AIS),a neurological injury resulting from blood clots,is the second most common cause of death worldwide.Novel therapeutics are urgently needed.Rapid developments in instrumentation and bioinformatics have resulted in increased use of mass spectrometry-based proteomics as an effective tool for the in-depth study of AIS.This review focuses on proteomics investigations of AIS in animal models.We highlight the study findings in system-wide protein abundance changes and molecular mechanisms underlying AIS with or without therapeutic intervention,as well as prestroke prognosis investigations.This review reveals that common molecular pathways related to ischemic injury and spontaneous recovery have been uncovered and part of AIS-changed proteins have been repeatedly identified,indicating the promise of proteomics in generating novel therapeutic targets and biomarker candidates.We also discuss challenges,alleviating strategies,and perspectives of mass spectrometry-based proteomics in AIS research and call for a broad application of systems-level investigations on preclinical AIS molecular mechanism elucidation,target discovery and validation,and therapeutics development.

关键词： Acute ischemic stroke ischemic molecular mechanism MCAO model proteomics stroke biomarker

Effect and Safety of Hydroxysafflor Yellow A for Injection in Patients with Acute ischemic stroke of Blood Stasis Syndrome: A Phase Ⅱ , Multicenter, Randomized, Double-Blind, Multiple-Dose, Active-Controlled Clinical Trial

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Chinese Journal of Integrative Medicine 2020年第6期26卷 420-427页

作者： HU Ming-zhe ZHOU Zi-yi ZHOU Zhong-yu LU Hui GAO Min LIU Long-min SONG Hai-qing LIN An-ji WU Qing-ming ZHOU Hong-fei LI Lei WANG Xia CAI Ye-feng The Second Clinical College of Guangzhou University of Chinese Medicine Guangzhou(510006)China Department of Neurology The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou(510120)China Department of Acupuncture and Moxibustion Hubei Provincial Hospital of Traditional Chinese MedicineWuhan(430061)China Department of Neurology Ruikang Hospital Affiliated to Guangxi University of Chinese MedicineNanning(530011)China Department of Neurology Guangdong Second Traditional Chinese Medicine HospitalGuangzhou(510095)China Department of Traditional Chinese Medicine Putuo HospitalShanghai University of Traditional Chinese MedicineShanghai(200062)China Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijing(100053)China Department of Traditional Chinese Medicine Xiamen Hospital of Traditional Chinese MedicineXiamen(361001)China Departm ent of Acupuncture and Moxibustion The Second Affiliated Hospital of Hunan University of Traditional Chinese MedicineChangsha(410005)China Departm ent of Neurology The Affiliated Hospital of Liaoning University of Traditional Chinese MedicineShenyang(110032)China School of Public Health Tongji Medical CollegeHuazhong University of Science and TechnologyW uhan(430030)China Youcare Pharm aceutical Group Dingcheng Branch Beijing(100176)China

Objective:To assess the effect and safety of Hydroxysafflor Yellow A for Injection(HSYAI)in treating patients with Acute ischemic stroke(AIS)and blood stasis syndrome(BSS).Methods:A multicenter,randomized,double-blind,multiple-dose,active-controlled phaseⅡtrial was conducted at 9 centers in China from July 2013 to September 2015.Patients with moderate or severe AIS and BSS were randomly assigned to low-,medium-,high-dose HSYAI groups(25,50 and 70 mg/d HSYAI by intravenous infusion,respectively),and a control group(Dengzhan Xixin Injection(灯盏细辛注射液,DZXXI)30 mL/d by intravenous infusion),for 14 consecutive days.The primary outcome was the Modified Rankin Scale(mRS)score 1 at days 90 after treatment.The secondary outcomes included the National Institute of Health stroke Scale(NIHSS)score 1,Barthel Index(BI)score 95,and BSS score reduced 30%from baseline at days 14,30,60,and 90 after treatment.The safety outcomes included any adverse events during 90 days after treatment.Results:Of the 266 patients included in the effectiveness analysis,66,67,65 and 68 cases were in the low-,medium-,and high-dose HSYAI and control groups,respectively.The proportions of patients in the medium-and high-dose HSYAI groups with mRS score 1 at days 90 after treatment were significantly larger than the control group(P0.05).Conclusions:HSYAI was safe and well-tolerated at all doses for treating AIS patients with BSS.The medium(50 mg/d)or high dose(75 mg/d)might be the optimal dose for a phaseⅢtrial.

关键词： hydroxysafflor yellow A Acute ischemic stroke randomized controlled trial blood stasis syndrome Chinese medicine

Xingnao Kaiqiao needling method for Acute ischemic stroke： a meta-analysis of safety and efficacy

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Neural Regeneration Research 2017年第8期12卷 1308-1314页

作者： Zhi-xin Yang Jia-hong Xie Ding-ding Liu Department of Traditional Chinese Medicine Chengde Medical University Chengde Hebei Province China Key Laboratory of Traditional Chinese Medicine Research and Development Institute of Traditional Chinese Medicine Chengde Medical University Chengde Hebei Province China School of Traditional Chinese Medicine North China University of Science and Technology Tangshan Hebei Province China

OBJECTIVE： To evaluate the effectiveness and safety of the Xingnao Kaiqiao needling method for treating Acute ischemic stroke.DATA SOURCES： We retrieved relevant randomized controlled trials involving Xingnao Kaiqiao acupuncture for treatment of Acute ischemic stroke. The China National Knowledge Infrastructure, Weipu Information Resources System, Wanfang Medical Data System, Chinese Biomedical Literature Database, Cochrane Library, and Pub Med were searched from June 2006 to March 2016.DATA SELECTION： We analyzed randomized and semi-randomized clinical controlled trials that compared Xingnao Kaiqiao acupuncture with various control treatments, such as conventional drugs or other acupuncture therapies, for treatment of Acute ischemic stroke. The quality of articles was evaluated according to the Cochrane Handbook for Systematic Reviews of Interventions（Version 5.1）, and the study was carried out using Cochrane system assessment methods. Rev Man 5.2 was used for the meta-analysis of the included studies.OUTCOME MEASURES： The mortality rate, disability rate, activities of daily living（Barthel Index）, and clinical efficacy were observed.RESULTS： Twelve studies met the inclusion criteria for this review. The meta-analysis showed that between Xingnao Kaiqiao acupuncture and the control treatment, Xingnao Kaiqiao acupuncture reduced the disability rate [risk ratio（RR） = 0.51, 95% confidence interval（CI） = 0.27-0.98, z = 2.03, P 〈 0.05], elevated the activities of daily living（weighted mean difference = 12.23, 95% CI： 3.66-20.08, z = 2.80, P 〈 0.005）, and had greater clinical efficacy（RR = 1.61, 95% CI： 1.23-2.09, z = 3.53, P 〈 0.0004）. However, there was no significant difference in mortality rate（RR = 0.61, 95% CI： 0.15-2.45, z = 0.70, P 〉 0.05）. CONCLUSION： The Xingnao Kaiqiao needling method is effective and safe for Acute ischemic stroke. However, there was selective bias in this study, and the likelihood of measurement bias is high. Thus, more high-quality randomized controlled trials are needed to provide reliabl

关键词： nerve regeneration Xingnao Kaiqiao needling method Acute ischemic stroke meta-analysis systematic review activities of daily living Barthel index mortality disability rate clinical e^cacy neuralregeneration

Dyslipidemia and Outcome in Patients with Acute ischemic stroke

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Biomedical and Environmental Sciences 2014年第2期27卷 106-110页

作者： XU Tian ZHANG Jin Tao YANG Mei ZHANG Huan LIU Wen Qing KONG Yan XU Tan ZHANG Yong Hong Department of Epidemiology School of Public Health Medical College of Soochow University Department of Neurology Chinese PLA 88 Hospital Department of Ophthalmology Affiliated Hospital of Nantong University

Objective To study the relationship between dyslipidemia and outcome in patients with Acute ischemic stroke. Methods Data about 2 568 patients with Acute ischemic stroke were collected from 4 hospitals in Shandong Province from January 2006 to December 2008. National Institute of Health stroke Scale （NIHSS）〉10 at discharge or death was defined as the outcome. Effect of dyslipidemia on outcome in patients with Acute ischemic stroke was analyzed by multivariate logistic regression analysis and propensity score-adjusted analysis, respectively. Results The serum levels of TC, LDL-C, and HDL-C were significantly associated with the outcome in patients with Acute ischemic stroke. Multivariate logistic regression analysis and propensity score-adjusted analysis showed that the ORs and 95% CIs were 3.013 （1.259, 7.214）/2.655 （1.298, 5.43）, 3.157 （1.306, 7.631）/3.405 （1.621, 7.154）, and 0.482 （0.245, 0.946）/0.51 （0.282, O.921）, respectively, for patients with Acute ischemic stroke. Hosmer-Lemeshow goodness-of-fit test showed no significant difference in observed and predicted risk in patients with Acute ischemic stroke （chi-square=8.235, P=0.411）. Conclusion Serum levels of TC, LDL-C, and HDL-C are positively related with the outcome in patients with Acute ischemic stroke.

关键词： Dyslipidemia Acute ischemic stroke Outcome Multivariate logistic regression analysis Propensity score-adjusted analysis

Acute ischemic stroke combined with Stanford type A aortic dissection:A case report and literature review

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World Journal of Clinical Cases 2022年第22期10卷 8009-8017页

作者： Zhi-Yang He Lin-Peng Yao Xiao-Ke Wang Nai-Yun Chen Jun-Jie Zhao Qian Zhou Xiao-Feng Yang Department of Emergency and Trauma Center The International Medical CenterThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina Department of Radiology The First Affiliated HospitalZhejiang University school of MedicineHangzhou 310003Zhejiang ProvinceChina

BACKGROUND acute aortic dissection(AAD)is a high mortality disease that can lead to Acute ischemic strokes(AIS).Some of the patients with AAD combined with AIS initially present with neurological symptoms,which can easily lead to missed or delayed AAD diagnosis.This is attributed to the lack of physician awareness or the urgency of patient thrombolysis.Intravenous administration of thrombolytic therapy(IVT)for AAD is associated with poor prognostic outcomes.We report a patient with AIS combined with AAD who developed a massive cerebral infarction after receiving IVT for a missed AAD diagnosis.CASE SUMMARY A 49-year-old man was admitted to a local hospital with an acute onset of leftsided limb weakness accompanied by slurred speech.The patient had a history of hypertension that was not regularly treated with medication.Physical examination revealed incomplete mixed aphasia and left limb hemiparesis.Cranial computed tomography(CT)scan showed bilateral basal ganglia and lateral ventricular paraventricular infarct lesions.The patient was diagnosed with AIS and was administered with IVT.After IVT,patient’s muscle strength and consciousness deteriorated.From the local hospital,he was referred to our hospital for further treatment.Emergency head and neck CT angiography(CTA)scans were performed.Results showed multiple cerebral infarctions,and aortic dissection in the ascending aorta,innominate artery,as well as in the right common carotid artery.Then,the CTA of thoracoabdominal aorta was performed,which revealed a Stanford type A aortic dissection and aortic dissection extending from the aortic root to the left external iliac artery.Laceration was located in the lesser curvature of the aortic arch.AAD complicated with AIS was considered,and the patient was immediately subjected to cardiovascular surgery for treatment.The next day,the patient underwent aortic arch and ascending aortic replacement and aortic valvuloplasty.CONCLUSION Clinical manifestations for AAD combined with AIS are diverse.Some patients may not exhibit

关键词： acute aortic dissection Acute ischemic stroke Intravenous thrombolysis Ultrasound evaluation Case report

Image-based visualization of stents in mechanical thrombectomy for Acute ischemic stroke:Preliminary findings from a series of cases

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World Journal of Clinical Cases 2023年第21期11卷 5047-5055页

作者： Qing-Yang Yao Mao-Lin Fu Qing Zhao Xiao-Ming Zheng Kai Tang Li-Ming Cao Department of Neurology The First Hospital of Quanzhou Affiliated to Fujian Medical UniversityQuanzhou 362000Fujian ProvinceChina Department of Neurology The 910th Hospital of the Joint Logistics Support Force of the Chinese PLAQuanzhou 362000Fujian ProvinceChina Department of Neurology The First Affiliated Hospital of Shenzhen UniversityShenzhen 518000Guangdong ProvinceChina Hunan Provincial Key Laboratory of The Research and Development of Novel Pharmaceutical Preparations Changsha Medical UniversityChangsha 410219Hunan ProvinceChina

BACKGROUND Mechanical thrombectomy is the most effective treatment for great cerebral artery embolization within a set time window.Typically,an arteriogram does not show the localization of the stent after release and whether a thrombus is captured or not.Thus,improving the visualization of a stent in interventional therapy will be helpful for clinicians.AIM To analyze stent imaging findings to enhance clinicians’understanding of a special circumstance,wherein a Solitaire AB retrievable stent was visible during the imaging of a thrombus capture that improved the success rate of stent-based mechanical thrombectomy.METHODS This was a retrospective study with four Acute ischemic stroke(AIS)patients who underwent stent-based mechanical thrombectomy.RESULTS Patient 1 was a 64-year-old man admitted after 5 h of confusion;angiography revealed basilar artery occlusion.We inserted a stent into the left posterior cerebral artery-P2 segment and visualized the expanded stent that successfully captured a thrombus.Patient 2 was a 74-year-old man admitted with confusion,which lasted approximately 3 h.Angiography revealed a left middle cerebral artery(MCA)-M1 segment occlusion.A stent was deployed in the distal M2 segment,and we could visualize the stent by capturing the thrombus.Patient 3 was a 74-year-old woman admitted after experiencing left hemiplegia for 3 h.We deployed a stent at the distal right MCAM2 segment,and the developing stent captured a large thrombus.Patient 4 was an 82-year-old man who presented with confusion for 3 h.A developing stent was placed in the distal left MCA-M1 segment,which captured a large thrombus and several fragmented thrombi.CONCLUSION To the best of our knowledge,this is the first report of stent imaging in patients with AIS.We demonstrated the usefulness and substantial potential of stent imaging in stent-based mechanical thrombectomy for AIS.

关键词： Digital subtraction angiography Solitaire AB stent Acute ischemic stroke Stent-based mechanical thrombectomy Visualization of stents