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。     

Neuronal plasticity after ischemic preconditioning and TIA-like preconditioning ischemic periods

Transient ischemic attacks (TIAs) have recently become the center of attention since they are thought to share some characteristics with experimental ischemic preconditioning (IPC). This phenomenon describes the situation that a brief, per se harmless, cerebral ischemic period renders the brain resistant to a subsequent severe and normally damaging ischemia. Preconditioning (PC) is not restricted to the brain but also occurs in other organs. Furthermore, apart from a short ischemia, the PC event may comprise nearly any noxious stimulus which, however, must not exceed the threshold to tissue damage. In the last two decades, our knowledge concerning the underlying molecular basis of PC has substantially grown and there is hope to potentially imitate the induction of an endogenous neuroprotective state in patients with a high risk of cerebral ischemia. While, at present, there is virtually no neuropathological data on changes after TIAs or TIA-like PC ischemic periods in human brains, the following review will briefly summarize the current knowledge of plastic neuronal changes after PC in animal models, still awaiting their detection in the human brain.     

Remote ischemic conditioning approach for the treatment of ischemic stroke

Stroke is the leading cause of disability and death in North America.There has been growing interest in identifying neuroprotective strategies to reduce ischemic burden in patients with acute ischemic stroke.However,despite extensive clinical trials,no neuroprotective agent has been found for prevention of ischemic damage.Remote ischemic preconditioning(RIC)is a promising non-invasive strategy that has been proven to provide renal and cardioprotection and has recently found to have a potential broad application in the treatment of neurovascular disease,which has bee linked to its possible effects on the release and activation of endogenous neuroprotective substances against the ischemia/reperfusion injuries in experimental studies.This endogenous neuroprotection might vaccinate neural tissues against effects of acute IR following primary infarction insult.Regardless of the method of RIC administration,through manual or automated blood pressure cuff,RIC procedure is inexpensive and easy to use.Based on the experimental and clinical data,application of RIC avoids possible adverse effects and interactions associated with chemical pharmacological agents.In previous clinical studies RIC was safe and associated with only minor transient adverse effects in few cases,including petechia and minor limb pain,which were mostly resolved shortly after completing the treatment.     

Pediatric ischemic stroke

Journal of Neurology -     

皮质下缺血性抑郁

自1997年Krishnann和Alexopoulos分别提出了"血管性抑郁"的假说后,血管性抑郁受到了广泛的关注.此后,在对其中的MRI定义的血管性抑郁的研究发现,皮质下缺血性血管病变(subcortical ischemic vascular disease, SIVD)不仅与认知损害及死亡高风险有关,其在血管性抑郁的发展过程中也起着重要作用.     

Pontine ischemic rarefaction

To investigate apparently asymptomatic, bilateral symmetrical predominantly pontine hyperintensities (PHI) on magnetic resonance imaging (MRI) scans in elderly patients, we examined the pons histopathologically in two brains of elderly hypertensives with PHI, and in three without PHI, on postmortem MRI scans. We also reviewed 85 serial in vivo MRI scans of patients over 60 and compared scan findings, vascular risk factors, and clinical symptoms between patients with PHI and a control group. A subcortical arteriosclerotic encephalopathy (SAE)-like pathology was present in the pons in only the two autopsy brains with PHI and corresponded with the location of PHI on the postmortem MRI scans and with the most frequent sites of PHI on in vivo scans. SAE also involved the hemispheric white matter in one of the autopsy brains. Five of 16 (31%) patients with, and 4 of 69 (6%) without, PHI on in vivo MRI scans had marked periventricular hyperintensity (PVHI) compatible with SAE (p = 0.01). We conclude that an SAE-like pathology may be seen in the pons in elderly hypertensives and this pathology is probably the cause of PHI seen on MRI scans of patients over 60 years of age.     

Experimental ischemic myopathy

The acute and chronic morphological changes in ischemic rat solei and gastrocnemii produced by abdominal aortic ligation were studied with histochemical and electron microscopic techniques. By light microscopy, the fully developed lesions 4 days after aortic ligation consisted of grouped or scattered necrotic fibers undergoing phagocytosis as well as regenerating fibers. By electron microscopy, the earliest lesions seen 2 hr after aortic ligation, consisted of trilaminar plates in the intracristal space of mitochondria and muscle cell necrosis as evidenced by interruption of the plasma membrane and dissolution of the Z-discs. From 18 hr onward post ligation, prominent Z-disc streaming was also present. Regenerating fibers were numerous by 4 days post-ligation. Six and 12 weeks after aortic ligation prominent “type grouping” was the only significant alteration by histochemistry. An increase of the endomysial connective tissue was conspicuously absent.The ischemic lesions were much more severe in amount and degree in the solei than in the gastrocnemii. Sciatic nerve section, Achilles tenotomy and skeletal fixation of the ankles and knees prevented ischemic lesions as viewed with light microscope. A comparison of the experimental ischemic lesions to the lesions of early or late Duchenne dystrophy revealed significant dissimilarities, while muscle biopsies in childhood dermatomyositis share many ultrastructural features of experimental ischemic myopathy.     

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.     

Early ischemic lesion recurrence within a week after acute ischemic stroke

Previous observations suggested that multiple ischemic lesions on diffusion-weighted imaging (DWI) are common in acute stroke patients. We hypothesized that a source of these multiple lesions was the recurrence of ischemic lesions within a week after a clinically symptomatic stroke. We analyzed 99 acute ischemic stroke patients scanned within 6 hours of onset and at subsequent times within the first week. Ischemic lesion recurrence was defined as any new lesion separate from the index lesion. Recurrent lesions occurring outside initial perfusion deficit were termed 'distant lesion recurrence'. We estimated the hazard ratio (HR) of recurrence associated with clinical and imaging characteristics using log-rank test. Any lesion recurrence was found in 34%, with distant lesion recurrence in 15%, while clinical recurrence was evident in 2%. Initial multiple DWI lesions were associated with any lesion recurrence (HR, 2.83; 95% confidence interval [CI], 1.65-10.29; p = 0.002) and with distant lesion recurrence (HR, 5.99; 95% CI, 4.05-64.07; p < 0.0001). Large-artery atherosclerosis was the most frequent stroke subtype associated with any lesion recurrence (p = 0.026). These results may indicate a prolonged state of increased ischemic risk over the first week and suggest DWI as a possible surrogate measure for recurrent stroke.     

Arterial ischemic stroke in an adolescent with presumed perinatal ischemic stroke

The risk of recurrent ischemic stroke after presumed perinatal stroke and the risk factors for such recurrence are rarely reported. Here, we present an adolescent with a history of presumed perinatal stroke who presented with arterial ischemic stroke recurrence at the age of 15 years. Hereditary thrombophilia screening performed at the time of his stroke recurrence demonstrated protein S deficiency. No evidence-based consensus guidelines on thrombophilia screening in children with presumed perinatal stroke exist, nor has the role of secondary prophylaxis been addressed. There is a risk of stroke recurrence after presumed perinatal stroke, and routine thrombophilia screening may identify those children who are at higher risk for recurrence and who might therefore benefit from secondary prophylaxis. Clear guidelines should be developed to standardize investigations and management of children with presumed perinatal ischemic stroke.     

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。     

P-选择素与缺血性脑卒中

血小板活化在缺血性脑卒中的发生、发展过程中起着重要作用,P-选择素（CD62p）的表达是血小板活化的标志。抗CD62p治疗可以减轻缺血性脑损伤症状。因此,研究CD62p在缺血性脑卒中的发生和卒中后再损伤过程中的作用,对缺血性脑卒中的防治具有重要意义。     

缺血性卒中后的神经炎性反应

神经炎性反应在缺血性卒中后的病理损伤中起重要作用。越来越多的证据表明,神经炎性反应是一把"双刃剑",在加重急性期卒中脑损伤的同时,亦可促进卒中后的神经修复。本文阐述了缺血性卒中后神经炎性反应的关键因素,如炎性细胞、炎性介质和黏附分子的变化,探讨了其可能的神经损伤及神经保护作用;同时,对缺血性卒中后神经炎性反应相关研究的进展及前景进行了综述。     

The telodiencephalic ischemic syndrome

Summary A new cerebral syndrome is described which occurs rather frequently with ischemia affecting the common pathway of the internal carotid and middle cerebral arteries. The syndrome consists of contralateral brachiofacial hemiparesis, possibly with hemianopia and/or aphasia, and ipsilateral thermoregulatory hemihypohidrosis with an ipsilateral central Horner syndrome. It is caused by an ischemic lesion of the crossed pathways descending from the cerebrum and the uncrossed hypothalamo-spinal sympathetic pathways descending through the subthalamic region. It is suggested to name the syndrome telodiencephalic ischemic syndrome.

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Zusammenfassung Es wird ein neues zerebrales Syndrom vorgestellt, das bei Ischämien in der Strombahn der Arteria carotis interna-cerebri media relativ häufig vorkommt. Das Syndrom besteht aus der bekannten kontralateralen brachiofacialen Hemiparese, eventuell mit Hemianopsie und/oder Aphasie und einer ipsilateralen thermoregulatorischen Hemihypohidrose mit ipsilateralem zentralen Horner-Syndrom. Es entsteht durch ischämische Schädigung der vom Großhirn absteigenden kreuzenden Bahnen und der durch den subthalamischen Bezirk absteigenden nicht-kreuzenden hypothalamo-spinalen sympathischen Bahn. Es wird vorgeschlagen, das Syndrom telo-diencephales Ischämie-Syndrom zu nennen.