Ischemic stroke: experimental models and reality.
Ischemic stroke: experimental models and reality.
复制标题
缺血性中风：实验模型和现实。
DOI：
10.1007/s00401-017-1667-0
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发表时间：
2017-02
影响因子：
12.7
通讯作者：
Sommer CJ
中科院分区：
文献类型：
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作者：
Sommer CJ
绝大多数脑卒中病例是由脑血管的暂时或永久性闭塞（“缺血性卒中”）引起的，最终导致脑梗死。最终的梗死面积和神经学结果取决于多种因素，如缺血的持续时间和严重程度、侧支系统的存在和足够的全身血压、梗死的病因和定位，但也取决于年龄、性别、与各自的多种药物治疗的合并症和遗传背景。因此，缺血性卒中是一种高度复杂和异质性的疾病。很明显，中风的实验模型只能涵盖这种多方面疾病的个别特定方面。对缺血样条件诱导的主要分子途径的基本理解已经来自体外研究。中风研究中最常用的体内模型之一是啮齿动物大脑中动脉（MCA）闭塞的血管内缝合或细丝模型，这会导致MCA区域的可重现性梗死。它不需要颅骨切除术，并允许通过撤回闭塞细丝进行再灌注。尽管迅速恢复血流与自发性人类卒中的病理生理学相去甚远，但它更接近于机械血栓切除术的治疗情况，预计机械血栓切除术将越来越多地应用于卒中患者。直接短暂或永久性脑动脉闭塞是一种替代方法，但需要颅骨切除术。内皮素-1是一种有效的血管收缩剂，应用内皮素-1可以在几乎任何脑区诱导短暂的局灶性缺血，并经常用于腔隙性卒中模型。局限性和高度可重复的皮质病变是光血栓性卒中的特征，其中梗死是通过完整颅骨全身给予染料的光活化诱导的。这个模型的主要缺点是几乎完全没有半影。最接近模拟人类中风的两种模型是各种栓塞性中风模型和自发性中风模型。接近现实是有代价的，而且沿着的是梗死面积和位置的更高变异性，以及自发模型中不可预测的卒中发作，而栓塞凝块模型中不可预测的再灌注。
The vast majority of cerebral stroke cases are caused by transient or permanent occlusion of a cerebral blood vessel (“ischemic stroke”) eventually leading to brain infarction. The final infarct size and the neurological outcome depend on a multitude of factors such as the duration and severity of ischemia, the existence of collateral systems and an adequate systemic blood pressure, etiology and localization of the infarct, but also on age, sex, comorbidities with the respective multimedication and genetic background. Thus, ischemic stroke is a highly complex and heterogeneous disorder. It is immediately obvious that experimental models of stroke can cover only individual specific aspects of this multifaceted disease. A basic understanding of the principal molecular pathways induced by ischemia-like conditions comes already from in vitro studies. One of the most frequently used in vivo models in stroke research is the endovascular suture or filament model in rodents with occlusion of the middle cerebral artery (MCA), which causes reproducible infarcts in the MCA territory. It does not require craniectomy and allows reperfusion by withdrawal of the occluding filament. Although promptly restored blood flow is far from the pathophysiology of spontaneous human stroke, it more closely mimics the therapeutic situation of mechanical thrombectomy which is expected to be increasingly applied to stroke patients. Direct transient or permanent occlusion of cerebral arteries represents an alternative approach but requires craniectomy. Application of endothelin-1, a potent vasoconstrictor, allows induction of transient focal ischemia in nearly any brain region and is frequently used to model lacunar stroke. Circumscribed and highly reproducible cortical lesions are characteristic of photothrombotic stroke where infarcts are induced by photoactivation of a systemically given dye through the intact skull. The major shortcoming of this model is near complete lack of a penumbra. The two models mimicking human stroke most closely are various embolic stroke models and spontaneous stroke models. Closeness to reality has its price and goes along with higher variability of infarct size and location as well as unpredictable stroke onset in spontaneous models versus unpredictable reperfusion in embolic clot models.