Neuroregenerative effects of BMP7 after stroke in rats.
Previous reports have indicated that the expression of bone morphogenetic protein-7 (BMP7) is enhanced after ischemic injury in brain. This upregulation may induce endogenous neurorepair in the ischemic brain. 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 1 h. 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 fourth and fifth 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 1 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.
Chou
Jenny
J
National Institute on Drug Abuse, IRP, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.
Harvey
Brandon K
BK
Chang
Chen-Fu
CF
Shen
Hui
H
Morales
Marisela
M
Wang
Yun
Y
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000627:therapeutic use*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count; D002544:Cerebral Infarction / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013778:Tetrazolium Salts; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000627:therapeutic use*; D016896:Treatment Outcome
C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D018696:Neuroprotective Agents; D013778:Tetrazolium Salts; D016212:Transforming Growth Factor beta; C009591:triphenyltetrazolium; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine