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.
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