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.     

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.     

Pediatric ischemic stroke

Journal of Neurology -     

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.     

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.     

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 spin label imaging of acute ischemic stroke and transient ischemic attack

Since acute stroke and transient ischemic attack (TIA) are disruptions of brain hemodynamics, perfusion neuroimaging might be of clinical utility. Recently, arterial spin labeling (ASL), a noncontrast perfusion method, has become clinically feasible. It has advantages compared to contrast bolus perfusion-weighted imaging (PWI) including lack of exposure to gadolinium, improved quantitation, and decreased sensitivity to susceptibility and motion. Drawbacks include reduced signal-to-noise and high sensitivity to arterial transit delays. However, this sensitivity can enable visualization of collateral flow. This article discusses ASL findings in patients with acute stroke and TIA, focusing on typical appearances, common artifacts, and comparisons with PWI.     

Neuroprotection targeting ischemic penumbra and beyond for the treatment of ischemic stroke

Neuroprotection to attenuate or block the ischemic cascade and salvage neuronal damage has been extensively explored for the treatment of ischemic stroke. In the last two decades, neuroprotective strategy has been evolving from targeting a signal pathway in neurons to protecting all neurovascular components and improving cell-cell and cell-extracellular matrix interaction that ultimately benefits the brain recovery after ischemic stroke. The progression from potentially reversible to irreversible injury in the ischemic penumbra has provided the opportunity to develop therapies to attenuate the ischemic stroke damage. Thus, the ischemic penumbra has been the main target for the current neuroprotective intervention. However, despite our increasing knowledge of the physiologic, mechanistic, and imaging characterizations of the ischemic penumbra, no effective neuroprotective therapy has been found so far for the treatment of ischemic stroke. The current acute neuroprotective approach focusing on the damaging mechanisms at the ischemic penumbra is greatly limited by the rapid evolution of the deleterious cascades in the ischemic penumbra. Neuroprotective intervention attempts to promote endogenous repairing in the transition zone of the penumbra for the therapeutic purposes may overcome the unrealistic therapeutic windows under the current neuroprotective strategy. In addition, increasing evidence has indicated ischemic stroke could induce long-lasing cellular and hemodynamic changes beyond the ischemic territory. It is unclear whether and how the global responses induced by the ischemic cascade contribute to the progression of cognitive impairment after ischemic stroke. The prolonged pathophysiological cascades induced by ischemic stroke beyond the ischemic penumbra might provide novel therapeutic opportunities for the neuroprotective intervention, which could prevent or slow down the progression of vascular dementia after ischemic stroke.