Mechanisms of Axonal Sprouting and Recovery in Intracerebral Hemorrhage

描述（由申请人提供）：中风是导致成人残疾的主要原因。中风是由直接阻断血液流动和出血引起的。脑出血是中风的第二大原因。脑出血（ICH）比非出血性中风有更少的比例恢复。然而，在脑出血中，有一个有限的初始恢复和恢复失去的脑功能的过程。脑出血功能恢复的机制尚未得到研究。该应用将确定脑出血后大脑中新连接的形成和恢复的机制。在非出血性中风中，新的连接在中风后的第一个月形成，这一过程被称为中风后轴突发芽。该应用方案的PI和其他实验室已经确定了中风后轴突发芽的分子机制，以及轴突发芽与功能恢复的关联。拟开展的研究将使用新开发的技术来确定脑出血后运动系统中形成的新连接模式，介导这种轴突发芽的基因系统，以及轴突发芽与通过这些基因系统介导的功能恢复之间的因果关系，从而确定可能作为神经修复治疗靶点的分子。

DESCRIPTION (provided by applicant): Stroke is the leading cause of adult disability. Stroke is produced both by direct blockade of blood flow and by hemorrhage. Intracerebral hemorrhage is the second leading cause of stroke. Intracerebral hemorrhage (ICH) has even less proportionate recovery than non-hemorrhagic stroke. However, in ICH there is a limited process of initial recovery and regaining of lost brain function. The mechanisms of functional recovery in ICH have not been studied. This application will determine the mechanisms for the formation of new connections and recovery in the brain after ICH. In non-hemorrhagic stroke, new connections are formed in the first month after the stroke, a process termed post-stroke axonal sprouting. The PI on this application proposal and other labs have identified the molecular mechanisms for axonal sprouting after stroke, and the association of axonal sprouting with functional recovery. The proposed studies will use newly developed techniques to identify the new patterns of connections that form in the motor system after ICH, the gene systems that mediate this axonal sprouting, and the causal link between axonal sprouting and functional recovery mediated through these gene systems, so as to determine molecules that may serve as therapeutic targets for neural repair in this disease. PUBLIC HEALTH RELEVANCE: Intracerebral hemorrhage is the second leading cause of stroke in the United States, and the most severe cause of stroke-related disability. There have been no studies on the mechanisms of re-connection and repair in the brain after intracerebral hemorrhage. The studies in this application will determine how the brain reconnects after stroke, the molecules that mediate this reconnection, and begin to identify potential new repair therapies for this disease.