缺血预处理诱导脑缺血耐受时间依赖性的实验研究

目的探讨缺血预处理诱导缺血耐受的时间依赖性及可能的机制。方法健康SD大鼠110只,采用随机数字表法分为假手术(SS)+大脑中动脉阻塞(MCAO)组(简称SS组)和缺血预处理(IP)+MCAO组(简称IP组),每组50只,另10只备用。将两组大鼠再随机分为5个亚组(n=10),IP组给予预缺血10 min后分别于6 h、24 h、3 d、7d、14 d后给予大脑中动脉完全阻塞22 h,再灌注2 h;SS组未进行缺血预处理,而单纯暴露颈总动脉处的解剖结构10 min,余步骤同IP组。采用Swanson间接法和Nick&Spot图像采集分析系统计算各组大鼠梗死体积,光镜下观察各组脑组织病理变化,采用免疫组化方法检测大鼠脑组织胶质纤维酸性蛋白(GFAP)、脑源性神经营养因子(BDNF)表达。结果给予10 min的大脑中动脉短暂的缺血预处理能够明显减少24 h、3 d、7 d1、4 d后再次缺血后的梗死体积(P<0.05),而6 h时间点脑梗死体积与SS组比较无统计学差异(P>0.05)。与SS组比较,IP组各时间点GFAP和BNDF阳性表达增多(P<0.05),且间隔3 d、7 d组增多明显(P<0.05),14 d后开始逐渐降低。结论 IP不但能引起神经系统损害,而且能够诱导缺血耐受的产生;IP诱导的缺血耐受对IP后3~7 d发生的再缺血损害保护作用最强。BDNF表达基本与缺血耐受的保护作用时间规律一致,提示BDNF可能是脑缺血耐受的重要机制之一。     

磁共振血管成像-弥散成像不匹配对预测急性缺血性脑卒中缺血半暗带的价值

目的研究急性缺血性脑卒中（AIS）超早期磁共振血管成像（MRA）一弥散成像（DWI）不匹配对预测缺血半暗带的价值。方法选择在发病6h内完成MRA、DWI及灌注成像（PWI）检查的大脑中动脉供血区脑梗死患者，MRA—DWI桓Ⅱ体女不匹配定义为MRA示大脑中动脉M1段闭塞，DWI的梗死体积〈25ml；MRA—DWI梗Ⅱ部＆不匹配定义为M1段闭塞，DWI的梗死部位评分（以Alberta梗死早期CT评分评价）≥7。结果共入选78例患者，MRA—DWI梗死体积不匹配预测：PWI—DWI不匹配的特异度为100％，灵敏度仅为46％。MRA—DWI梗Ⅱ部＆不匹配预测：PWI—DWI不匹配的特异度为100％，灵敏度为42．9％。结论AIS超早期MRA．DWI不匹配预测缺血半暗带有很高的特异度，可作为筛选进行溶栓治疗患者的手段。     

Neurobrucellosis as an exceptional cause of transient ischemic attacks

We report a series of four cases presented with transient ischemic attacks (TIA) or ischemic stroke as the predominant manifestation of neurobrucellosis (NB). Three of the patients were 20-28 years of age, and one patient was 53 years old. They all used to consume unpasteurized milk or its products. Two patients had systemic brucellosis in the past and received antibiotic treatment. Other causes of TIA including cardiac embolism, hypercoagulability, vascular malformations, systemic vasculitis, and infective endocarditis were excluded. NB was diagnosed with serological tests or cultures for Brucella in the cerebrospinal fluid. None of the patients had any further TIA after the initiation of specific treatment. NB should always be sought in young patients with TIA or ischemic stroke, especially if they have no risk factors for stroke and live in an endemic area for brucellosis, even if they do not have other systemic signs of brucellosis.     

Induction of ischemic tolerance as a promising treatment against diabetic retinopathy

Diabetic retinopathy is a leading cause of acquired blindness, and it is the most common ischemic disorder of the retina. Available treatments are not very effective. Efforts to inhibit diabetic reti- nopathy have focused either on highly specific therapeutic approaches for pharmacologic targets or using genetic approaches to change expression of certain enzymes. However, it might be wise to choose innovative treatment modalities that act by multiple potential mechanisms. The resis- tance to ischemic injury, or ischemic tolerance, can be transiently induced by prior exposure to a non-injurious preconditioning stimulus. A complete functional and histologic protection against retinal ischemic damage can be achieved by previous preconditioning with non-damaging isch- emia. In this review, we will discuss evidence that supports that ischemic conditioning could help avert the dreaded consequences that results from retinal diabetic damage.     

短暂性脑缺血发作与脑缺血耐受研究进展

脑缺血耐受是近年来的研究热点。短暂性脑缺血发作虽然使缺血性卒中危险增加,但同时可诱导神经细胞对再次缺血产生耐受。耐受的机制涉及血管因素、腺苷、兴奋性氨基酸、热休克蛋白、低氧诱导因子-1、促红细胞生成素、KATP通道等。临床观察显示,TIA的持续时间、发作频度、脑梗死间隔时间以及脑梗死体积等均与耐受的发生有关。     

缺血性脑卒中/短暂性脑缺血发作患者脑动脉病变分布相关危险因素分析

目的 探讨缺血性脑卒中(ischemic stroke,IS)/短暂性脑缺血发作(transient ischemic attack,TIA)脑动脉病变分布的相关危险因素.方法 对169例IS/TIA患者行颈部及颅内脑血管检查,记录血管病变危险因素如年龄、性别、高血压、糖尿病、长期吸烟、长期饮酒等病史,同时记录实验室、心电图、超声心动图、腹部B超、胸X片等检查结果.确定单变量与不同狭窄模式的相关性采用单变量Logistic回归分析,确定不同颅内外大动脉狭窄模式的独立危险因素采用多元逐步和多变量多项分类Logistic回归分析.结果 高龄、长期吸烟及高低密度脂蛋白(LDL-C)是颅内外大动脉狭窄的独立危险因素,发生颅内外大动脉狭窄的风险分别增加了1.83、6.918、1.656倍;脑卒中史(OR=4.816)、长期吸烟(OR=121.608)、高LDL-C(OR=3.067)是单纯颅内大动脉狭窄的独立危险因素;高龄(OR =2.486)、长期吸烟(OR=25.072)、高LDL-C(OR=5.160)是颅内外大动脉狭窄并存的独立危险因素;而高纤维蛋白原(OR =4.790)是单纯颅外大动脉狭窄的独立危险因素.结论 不同类型颅内外大动脉狭窄病变的独立危险因素不同.     

无创伤双后肢缺血后处理对移植胰腺缺血再灌注损伤的远隔保护

背景：缺血预处理及缺血后处理是近年来提出减轻缺血再灌注损伤有效方法。 目的：探讨无创伤双后肢缺血后处理对移植胰腺缺血再灌注损伤的影响及机制。 方法：18只糖尿病SD大鼠数字表法随机分为3组,对照组仅行开腹术;缺血再灌注组仅行胰腺移植;缺血后处理组,移植前行非创伤性双后肢缺血后处理。 结果与结论：缺血再灌注组血糖和胰腺组织中丙二醛水平均高于缺血后处理组(P < 0.01)、而超氧化物歧化酶活性低于缺血后处理组(P < 0.01);与缺血后处理组比较,缺血再灌注组胰腺组织凋亡指数明显增高(P < 0.01)。结果提示,无创伤双后肢缺血后处理对大鼠移植胰的缺血再灌注损伤具有保护作用,机制可能与可通过减少超氧化物歧化酶失活,从而清除氧自由基以及减少胰腺细胞凋亡等有关。     

神经保护药物干预短暂性脑缺血的临床分析

Transient ischemic attack(TIA) is an acute cerebrovascular incident,and is generally considered the best opportunity for early neuroprotective treatment against cerebral ischemia.This study retrospectively analyzed 80 patients with TIA(38 males and 42 females).Among 61 patients who received neuroprotective cerebrolysin treatment within 24 hours after TIA onset,13(21.31%) patients suffered subsequent strokes.Among 19 patients who received neuroprotective cerebrolysin treatment within 24-72 hours after TIA onset,seven(36.84%) developed cerebral infarction.There was a significant difference in the proportion of subsequent strokes between patients receiving cerebrolysin treatment within 24 hours and 24-72 hours after TIA onset(P = 0.438).These findings suggest that neuroprotective drugs administrated within 24 hours after TIA onset help reduce the incidence of subsequent strokes.The results demonstrate usefulness of the ABCD2 score at TIA patients in the determination of short-term and long-term cerebrovascular risk,including the frequency of subsequent ischemic cerebral infarctions up to 12 months.     

动脉内溶栓治疗急性缺血性脑卒中的临床分析

目的:探讨使用动脉内溶栓方法治疗急性缺血性脑卒中的效果。方法:回顾138例急性缺血性脑卒中患者,发病距接受治疗的时间为3～24h,采取超选择性动脉溶栓。结果:颈内动脉闭塞22例,大脑中动脉主干闭塞38例,大脑中动脉分支闭塞33例,大脑前动脉闭塞1例,椎基底动脉系统血管闭塞12支。脑血管造影未见异常32例。闭塞血管再通者,颈内动脉12例;大脑中动脉24例;大脑中动脉分支21例;椎基底动脉8例。8例患者因明显血管狭窄,治疗后予以球囊扩张,支架植入术。临床症状完全恢复或明显好转83例,溶栓后脑出血患者5例。结论:超选择动脉内溶栓是治疗急性缺血性脑卒中的有效方法。     

短暂性脑缺血发作患者的初步智力研究

目的 (1)探讨短暂性脑缺血发作(transient ischemic attacks,TIAs)患者在临床症状消失后是否遗留智力障碍;(2)明确颈内动脉系统TIAs与椎一基底动脉系统TIAs患者智力改变的异同。方法 对34例TIAs患者(其中颈内动脉系统TIAs和椎一基底动脉系统TIAs各17例)和34例对照分别进行修订韦氏成人智力量表检测。结果 (1)TIAs患者的各项量表评分均明显低于对照组(除图形拼凑项的P值小于0.05外,其余各项的P值均小于0.01);(2)除椎-基底动脉系统TIAs患者图片排列项的等值量表分明显低于颈内动脉系统TIAs外(P<0.05),其余各项评分两组无显著性差异(P>0.05)。结论 (1)TIAs患者在症状消失后可能依旧存在不同程度的智力障碍;(2)椎-基底动脉系统TIAs患者的智力(主要是理解能力)损害可能比颈内动脉系统TIAs患者更加严重。     

TIA与TIA形式的脑梗死的相关因素分析

目的分析TIA及TIA形式的脑梗死的临床特点,探索其临床相关因素。方法回顾性分析83例初步诊断为TIA并在症状首发后24 h内行常规MRI及DWI检查的患者,发病1周内行颈部动脉血管彩超、TCD。记录发病后7 d内的临床转归。根据DWI结果分为DWI+组及DWI-组,确定DWI阳性率。比较DWI+组及DWI-组临床特征差别。分析两组患者动脉粥样硬化斑块的部位、性质、数量及颅内外血管狭窄的部位、程度。结果DWI阳性率为36.1%。DWI阳性与动脉粥样硬化相关(P=0.03),与颈部动脉动脉粥样硬化斑块数目相关(P=0.04),TIA症状首发后7 d内,30.0%DWI+组患者TIA症状反复发作或表现为临床症状持续存在,高于DWI-组(22.6%)。结论临床表现为TIA的病例大于1/3急性期已经形成了脑梗死,动脉粥样硬化斑块数量越多,DWI阳性的可能性越大,DWI+的患者7 d内更易进展。     

A review of remote ischemic conditioning as a potential strategy for neural repair poststroke

Ischemic stroke is one of the major disabling health-care problem and multiple different approaches are needed to enhance rehabilitation, in which neural repair is the structural basement. Remote ischemic conditioning (RIC) is a strategy to trigger endogenous protect. RIC has been reported to play neuroprotective role in acute stage of stroke, but the effect of RIC on repair process remaining unclear. Several studies have discovered some overlapped mechanisms RIC and neural repair performs. This review provides a hypothesis that RIC is a potential therapeutic strategy on stroke rehabilitation by evaluating the existing evidence and puts forward some remaining questions to clarify and future researches to be performed in the field.     

Activation of p38 MAPK participates in brain ischemic tolerance induced by limb ischemic preconditioning by up-regulating HSP 70

This study investigates whether activation of p38 MAPK by the up-regulation of HSP 70 participates in the induction of brain ischemic tolerance by limb ischemic preconditioning (LIP). Western blot and immunohistochemical assays indicated that p38 MAPK activation occurred earlier than HSP 70 induction in the CA1 region of the hippocampus after LIP. P-p38 MAPK expression was up-regulated at 6 h and reached its peak 12 h after LIP, while HSP 70 expression was not significantly increased until 1 day and peaked 2 days after LIP. Neuropathological evaluation by thionin staining showed that quercetin (4 ml/kg, 50 mg/kg, intraperitoneal injection), an inhibitor of HSP 70, blocked the protective effect of LIP against delayed neuronal death that is normally induced by lethal brain ischemic insult, indicating that HSP 70 participates in the induction of brain ischemic tolerance by LIP. Furthermore, SB 203580, an inhibitor of HSP 70, inhibited HSP 70 activation in the CA1 region of the hippocampus induced by LIP either with or without the presence of subsequent brain ischemic insult. Based on the above results, it can be concluded that activation of p38 MAPK participates in the brain ischemic tolerance induced by LIP at least partly by the up-regulation of HSP 70 expression.     

C-reactive protein predicts further ischemic events in transient ischemic attack patients

BACKGROUND AND PURPOSE: Although patients with transient ischemic attack (TIA) experience cardiovascular events frequently, strong clinical predictors of recurrence are lacking. High-sensitivity C-reactive protein (hs-CRP) has been shown to be a powerful predictor of future first-ever and recurrent coronary and cerebral ischemic events. We aimed to investigate the relationship between hs-CRP and the risk of further ischemic events in TIA patients. METHODS: High-sensitivity C-reactive protein level was determined <24 h after symptom onset among 135 consecutive TIA patients and stroke recurrence or any new vascular event was recorded during 1 year follow-up period. RESULTS: A total of 38 (28.1%) patients experienced an end point event: 28 (20.7%) cerebral ischemic events, six (4.4%) heart ischemic events, four (3%) peripheral arterial disease, and nine (6.7%) vascular deaths. Cox proportional hazards multivariate analyses identified age [hazard ratio (HR) 1.07, 95% confidence interval (CI) 1.01-1.12, P = 0.01], large-artery occlusive disease (HR 2.73, 95% CI 1.16 to 6.41, P = 0.02) and hs-CRP> 4.1 mg/l (HR 2.81, 95% CI 1.12-7.10, P = 0.03) as independent predictors of stroke. Moreover, age (HR 1.05, 95% CI 1.01-1.10, P = 0.02), large-artery occlusive disease (HR 3.12, 95% CI 1.48-6.58, P < 0.01), coronary disease (HR 2.39, 95% CI 1.11-5.16, P = 0.03), and hs-CRP> 4.1 mg/l (HR 2.71, 95% CI 1.16-6.30, P = 0.02) were also independent predictors of any vascular event. CONCLUSIONS: High-sensitivity C-reactive protein serum level predicts further ischemic events following TIA. Routine CRP measurement might be a useful tool for identifying high-risk TIA patients in order to plan aggressive diagnostic protocols and prevention therapies.     

15-脂氧化酶及其mRNA在局灶性脑缺血预处理大鼠中作用机制的探讨

目的　观察局灶性脑缺血预处理对大鼠脑 15 -脂氧化酶 (15 - L O)表达及其 m RNA(15 - L O m RNA)转录的影响 ,探讨两者在诱导脑缺血耐受中的意义。方法　线栓法制备大鼠局灶性脑预缺血 -缺血再灌注模型 (PC-MCAO)及局灶性单纯脑缺血再灌注模型 (MCAO) ,各组于不同时程用免疫组化法检测 15 - L O的表达、原位杂交法检测 15 - L O m RNA的表达。结果　 PC- MCAO组较对应时程的 MCAO组 15 - L O m RNA及其蛋白 15 - L O的表达强度显著降低 (P<0 .0 5 )。结论　脑预缺血处理可致 15 - L O及其基因表达下调 ,这可能是局灶性脑缺血预处理诱导脑缺血耐受的机制之一。     

不同剂量阿托伐他汀对短暂性脑缺血发作转归的影响

目的：观察阿托伐他汀对短暂性脑缺血发作（T IA ）患者转归的影响。方法130例T IA患者随机分为高剂量（40 mg/d）阿托伐他汀治疗组（H组）和低剂量（10 mg/d）阿托伐他汀治疗组（L组）各65例,2组患者均给予相同的基础治疗。观察2组患者住院及随诊1 a期间T IA复发及形成梗死、新发冠脉事件、脑出血及死亡情况,并比较2组1 a点LDL水平。结果住院期间和随访期间,H组TIA复发率、梗死及新发冠脉事件发生率及LDL水平明显低于L组。结论高剂量（40 mg/d）阿托伐他汀能显著改善短暂性脑缺血患者的发作,值得临床推广。     

Transient ischemic attacks presenting as hemiballism.

Hemiballism is continuous, nonpatterned involuntary movement characterized by irregular, coarse, flinging movement involving the limbs on one side. Hemiballism is most commonly caused by stroke. However, very rarely a transient ischemic attack (TIA) presents as hemiballism. We describe 2 such patients with hemiballism presenting as TIA.