Davis Melissa F, Lay Christopher, Frostig Ron D
Department of Neurobiology & Behavior, University of California, Irvine, Irvine, CA, USA.
J Vis Exp. 2013 Jul 21(77):50418. doi: 10.3791/50418.
Stroke is a leading cause of death, disability, and socioeconomic loss worldwide. The majority of all strokes result from an interruption in blood flow (ischemia). Middle cerebral artery (MCA) delivers a great majority of blood to the lateral surface of the cortex, is the most common site of human stroke, and ischemia within its territory can result in extensive dysfunction or death. Survivors of ischemic stroke often suffer loss or disruption of motor capabilities, sensory deficits, and infarct. In an effort to capture these key characteristics of stroke, and thereby develop effective treatment, a great deal of emphasis is placed upon animal models of ischemia in MCA. Here we present a method of permanently occluding a cortical surface blood vessel. We will present this method using an example of a relevant vessel occlusion that models the most common type, location, and outcome of human stroke, permanent middle cerebral artery occlusion (pMCAO). In this model, we surgically expose MCA in the adult rat and subsequently occlude via double ligature and transection of the vessel. This pMCAO blocks the proximal cortical branch of MCA, causing ischemia in all of MCA cortical territory, a large portion of the cortex. This method of occlusion can also be used to occlude more distal portions of cortical vessels in order to achieve more focal ischemia targeting a smaller region of cortex. The primary disadvantages of pMCAO are that the surgical procedure is somewhat invasive as a small craniotomy is required to access MCA, though this results in minimal tissue damage. The primary advantages of this model, however, are: the site of occlusion is well defined, the degree of blood flow reduction is consistent, functional and neurological impairment occurs rapidly, infarct size is consistent, and the high rate of survival allows for long-term chronic assessment.
中风是全球范围内导致死亡、残疾和社会经济损失的主要原因。所有中风中的大多数是由血流中断（缺血）引起的。大脑中动脉（MCA）将大部分血液输送到皮质的外侧表面，是人类中风最常见的部位，其供血区域内的缺血可导致广泛的功能障碍或死亡。缺血性中风的幸存者常常遭受运动能力丧失或受损、感觉缺陷和梗死。为了捕捉中风的这些关键特征，从而开发有效的治疗方法，人们非常重视大脑中动脉缺血的动物模型。在此，我们介绍一种永久性阻塞皮质表面血管的方法。我们将以一种相关血管阻塞的示例来介绍这种方法，该示例模拟了人类中风最常见的类型、位置和结果，即永久性大脑中动脉阻塞（pMCAO）。在这个模型中，我们通过手术暴露成年大鼠的大脑中动脉，随后通过双重结扎和切断血管来进行阻塞。这种pMCAO阻断了大脑中动脉的近端皮质分支，导致大脑中动脉所有皮质供血区域（大部分皮质）缺血。这种阻塞方法也可用于阻塞皮质血管的更远端部分，以实现针对更小皮质区域的更局灶性缺血。pMCAO的主要缺点是手术操作具有一定的侵入性，因为需要进行小开颅手术来暴露大脑中动脉，不过这只会造成最小程度的组织损伤。然而，这个模型的主要优点是：阻塞部位明确，血流减少程度一致，功能和神经损伤迅速出现，梗死大小一致，并且高存活率允许进行长期慢性评估。
