Institute of Neuropathology, University Medical Center of the Johannes Gutenberg-University Mainz; Focus Program Translational Neuroscience (FTN) and Rhine Main Neuroscience Network (rmn2), Langenbeckstrasse 1, 55131, Mainz, Germany.
Acta Neuropathol. 2017 Feb;133(2):245-261. doi: 10.1007/s00401-017-1667-0. Epub 2017 Jan 7.
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.
绝大多数脑卒中是由于脑动脉短暂或永久性闭塞（“缺血性脑卒中”），最终导致脑梗死。最终的梗死面积和神经功能结局取决于许多因素，如缺血的持续时间和严重程度、侧支循环的存在和足够的全身血压、梗死的病因和定位，还取决于年龄、性别、合并症及其相应的多药物治疗和遗传背景。因此，缺血性脑卒中是一种高度复杂和异质的疾病。很明显，脑卒中的实验模型只能涵盖这种多方面疾病的个别特定方面。对类似于缺血条件诱导的主要分子途径的基本了解已经来自于体外研究。在脑卒中研究中，最常用的体内模型之一是啮齿动物的血管内缝线或纤维模型，其中大脑中动脉（MCA）的闭塞导致 MCA 区域内可重复的梗死。它不需要开颅手术，并允许通过拔出闭塞的纤维来再灌注。尽管迅速恢复血流与自发性人类脑卒中的病理生理学相去甚远，但它更接近机械血栓切除术的治疗情况，预计这种治疗方法将越来越多地应用于脑卒中患者。直接短暂或永久性闭塞脑动脉是另一种方法，但需要开颅手术。内皮素-1 的应用，一种有效的血管收缩剂，可以在几乎任何脑区诱导短暂的局灶性缺血，常用于腔隙性脑卒中的模型。光血栓性脑卒中的特征是局限且高度可重复的皮质病变，其中梗死是通过系统给予的染料通过完整颅骨的光激活而诱导的。这种模型的主要缺点是几乎完全没有半影区。最接近人类脑卒中的两种模型是各种栓塞性脑卒中模型和自发性脑卒中模型。与现实的接近是有代价的，并且伴随着梗死面积和位置的更大变异性，以及自发性模型中不可预测的中风发作和栓塞性血栓模型中不可预测的再灌注。
