GROWTH FACTORS INFLUENCE STROKE RECOVERY

局灶性中风，即由于大脑动脉闭塞而导致某一区域脑组织死亡，在美国和世界各地仍然是一个主要的公共卫生问题。中风可能导致运动、认知、语言或视觉功能障碍。虽然常常是不完整的，但在一定程度上对剩余完整的大脑进行了功能和结构的重组。在以前的研究中，我们已经研究了多肽生长因子作为分子信号启动卒中后康复潜在的分子和细胞事件级联反应的作用。特别是，我们发现，外源性给予重组碱性成纤维细胞生长因子(BFGF)或成骨蛋白-1(OP-1，BMP-7)可促进局灶性卒中啮齿动物模型的功能恢复，即使在卒中发生很长时间后给予也是如此。这种效果不是由于梗塞体积的减少，而是可能是由于促进了未受损伤的完好大脑中新神经元的萌发和突触的形成。在拟议的研究中，我们将：(1)研究外源性bFGF和OP-1治疗促进功能恢复的剂量和时间窗特征；(2)检测阻断内源性bFGF和OP-1对功能恢复的抑制作用；(3)探讨bFGF和OP-1促进功能恢复的分子和细胞机制，包括新的轴突和树突萌发和突触形成的分子标志物的表达研究和形态学研究。这些研究有望对卒中后恢复的分子机制有新的认识，并可能导致多肽生长因子作为一种新的分子治疗手段来促进卒中恢复。

Focal stroke, i.e., the death of a region of brain tissue due to occlusion of a cerebral artery, remains a major public health problem in the U.S. and around the world. Stroke may cause deficits of motor, cognitive, language, or visual function. Although often incomplete, some degree of functional and structural reorganization of the remaining intact brain. In previous studies, we have investigate the role of polypeptide growth factors as molecular signals initiating the cascade of molecular and cellular events underlying recovery after stroke. In particular, we found that the exogenous administration of recombinant basic fibroblast growth factor (bFGF) or osteogenic protein-1 (OP-1, BMP-7) enhanced functional recovery in rodent models of focal stroke, even when given long after stroke had occurred. This effect was not due to reduction in infract volume, but presumably to enhancement of new neuronal sprouting and synapse formation in the intact uninjured brain. In the proposed studies, we will: (1) investigate the dose and time window characteristics of exogenous bFGF and OP-1 treatment in enhancing functional recovery, (2) examine the effects of the blockade of endogenous bFGF and OP-1 in inhibiting recovery, and (3) explore the molecular and cellular mechanisms of enhancement of functional recovery by bFGF and OP-1, including studies of the expression of molecular markers of new axonal and dendritic sprouting and synapse formation, and morphological studies. These studies are expected to lead to new understanding of the molecular mechanisms of recovery after stroke, and may lead to the development of polypeptide growth factors as a new molecular treatment to enhance stroke recovery.