Mechanisms and Consequences of Hypertension after Stroke

描述（由申请人提供）： 我们最近的研究结果，强大的神经血管保护与早期血压（BP）降低中风后，促使我们，在这个竞争性的更新，继续阐明的机制，在中风后的几个小时内的BP管理的保护作用。我们的长期目标是了解缺血性卒中期间和之后脑中神经血管损伤的途径，以便为卒中患者设计和实施更好的治疗方法。在第一个资助期，我们确定了再灌注后血压降低具有神经血管保护作用，并且当采用血管紧张素阻滞剂时获得了最佳结果。这项研究的中心假设是，即使没有再灌注，通过早期降低血压实现的血管保护也会激活内源性存活蛋白，包括抗凋亡和血管生成途径的蛋白。我们计划测试我们的中心假设，并通过以下具体目标实现本申请的总体目标：具体目标#1：确定脑缺血后恢复和血压降低的程度取决于再灌注的存在和方法。我们的工作假设是，无论是否通过机械或溶栓实现再灌注，早期血压降低的神经血管保护作用持续存在。具体目标#2：确定脑缺血后早期血压降低诱导内源性存活途径的程度。我们的工作假设是，早期血压降低诱导一种“后调节”样状态，导致持续的血管保护，导致恢复。这种保护依赖于抗凋亡Akt和促血管生成VEGF活化。

DESCRIPTION (provided by applicant): Our recent findings of robust neurovascular protection with early blood pressure (BP) lowering after stroke has prompted us to, in this competitive renewal, continue to elucidate mechanisms of the protective effects of BP management in the hours after stroke. Our long term goal is to understand the pathways of neurovascular injury in the brain during and after ischemic stroke in order to design and implement better treatments for stroke patients. In the first funding period, we determined that BP lowering after reperfusion is neurovascularprotective, and the best outcomes are achieved when angiotensin blockade is employed. The central hypothesis for the proposed research is that vascular protection, accomplished by early BP lowering, activates endogenous survival proteins, including those of the antiapoptosis and angiogenic pathways, even without reperfusion. We plan to test our central hypotheses and accomplish the overall objectives of this application through the following specific aims: Specific Aim #1: Determine the extent to which recovery after cerebral ischemia and BP lowering is dependent upon the presence and method of reperfusion. Our working hypothesis is that the neurovascular protective effect of early BP lowering persists whether or not reperfusion is achieved, mechanically or by thrombolysis. Specific Aim #2: Determine the extent to which early BP lowering after cerebral ischemia induces endogenous survival pathways. Our working hypothesis is that early BP lowering induces a "post conditioning"- like state that results in persistent vascular protection, leading to recovery. This protection is reliant on antiapoptotic Akt and proangiogenic VEGF activation.