GROWTH FACTORS INFLUENCE STROKE RECOVERY

局灶性中风，即由于脑动脉闭塞导致的脑组织区域死亡，仍然是美国和世界各地的一个主要公共卫生问题。中风可能导致运动、认知、语言或视觉功能的缺陷。虽然经常不完整，但仍有一定程度的功能和结构重组。在之前的研究中，我们已经研究了多肽生长因子作为分子信号的作用，它启动了脑卒中后恢复的一系列分子和细胞事件。特别是，我们发现外源性给药重组碱性成纤维细胞生长因子（bFGF）或成骨蛋白-1 （p -1, BMP-7）可以增强局灶性中风啮齿动物模型的功能恢复，即使是在中风发生很久之后。这种影响不是由于脑梗死体积的减少，而可能是由于在完整的未受伤的大脑中，新神经元发芽和突触形成的增强。在建议的研究中，我们会：(1)研究外源性bFGF和OP-1处理促进功能恢复的剂量和时间窗特征；(2)研究内源性bFGF和OP-1阻断对功能恢复的抑制作用；(3)探索bFGF和OP-1促进功能恢复的分子和细胞机制，包括新轴突和树突发芽和突触形成分子标记的表达研究和形态学研究。这些研究有望导致对脑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脑卒中后恢复。

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.