The protective effect of Emmprin inhibition in acute cerebrovascular disease.

描述(申请人提供)：在美国，缺血性中风是导致持续性神经功能障碍的最常见原因。尽管付出了相当大的努力，但还没有一种治疗方法 一旦中风发生，可以减少伤害或恢复功能。在过去的几年里，我们对中风的看法已经转变为中风是一种神经血管疾病的概念，最近又转变为一种新的理论，即中风是一种真正的“全身性”疾病，在这种疾病中，外周炎症过程起着基础性作用。外周免疫细胞的继发性损伤越来越被认为是脑损伤、脑水肿和出血性转化的主要原因。这些细胞需要蛋白水解酶进入大脑，这个过程主要是通过激活基质金属蛋白酶(MMPs)来实现的。细胞外基质金属蛋白酶诱导物(EMMPRIN；CD147)是一种58 kDa的细胞表面糖蛋白，调节白细胞向脑内的转运。这个 拟议的工作将检查中风后CD147的调节，并确定功能阻断抗体是否可以减少损伤或血脑屏障(BBB)的破坏。这些效应将在老年动物(目标1)和慢性功能评估(目标2)中得到证实。这项初步工作将为研究其他基于生物的疗法治疗中风的可能性奠定基础。这些探索性研究有望为中风患者的治疗干预确定新的生物靶点。

DESCRIPTION (provided by applicant): Ischemic stroke is now the most frequent cause of persistent neurologic disability in the US. Despite considerable effort there are no therapies that can reduce injury or restore function once a stroke occurs. Over the past several years, our view of stroke as a "neuronal disease" has been transformed into the concept of stroke as a "neurovascular" disease, and more recently into the novel theory that stroke is truly a "systemic" disease in which peripheral inflammatory processes play a fundamental role. Secondary injury from the infiltration of peripheral immune cells is increasingly recognized as a major contributor to brain injury, edema and hemorrhagic transformation. These cells require proteases to transmigrate into the brain, a process mediated primarily by activation of matrix metalloproteinases (MMPs). Extracellular Matrix Metalloproteinase Inducer (EMMPRIN; CD 147) is a 58-kDa cell surface glycoprotein that regulates leukocyte trafficking into the brain. The proposed work will examine regulation of CD147 after stroke and determine if a function blocking antibody can reduce injury or blood brain barrier (BBB) breakdown. These effects will be confirmed in aged animals (Aim 1) and with chronic functional assessments (Aim 2). This preliminary work will set the stage for an investigation of the potential for other biologically based therapies to treat stroke. These exploratory studies will hopefully identify new biological targets for therapeutic intervention for patients with stroke.