Stroke and related vascular events can cause widespread damage to the central nervous system (CNS) and result in significant motor and cognitive impairments. It has been suggested that trophic factor treatment may reduce the extent of damage and restore damaged neurons following the injury. We have previously tested the effects of bone morphogenetic protein-7 (BMP-7), a member of the transforming growth factor-B superfamily of growth factors, in focal brain ischemic injury. We found BMP-7 to have profound neuroprotective effects after intraventricular administration. The purpose of this study was to examine neuroregenerative effects of BMP7 after ischemia /reperfusion injury. Adult Sprague-Dawley rats were anesthetized with chloral hydrate. Right middle cerebral artery (MCA) was transiently ligated with 10-O suture for one hour. One day after MCA occlusion, vehicle or BMP7 was infused to the contralateral cerebral ventricle. To identify possible neurogenesis, bromodeoxyurindine (BrdU) was systemically injected on the 4th and 5th days after MCA occlusion. Animals treated with BMP7 showed a rapid correction of body asymmetry and neurological deficits, suggesting BMP7 facilitates recovery after stroke. Animals were sacrificed at one month after stroke and brains were analyzed using immunohistological techniques. BMP7 treatment enhanced immunoreactivity of BrdU in the subventricular zone, lesioned cortex, and corpus callosum. These BrdU positive cells co-labeled with nestin and NeuN. Our behavioral and anatomical data suggest that BMP7 promotes neuroregeneration in stroke animals, possibly through the proliferation of new neuronal precursors after ischemia.
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