title: CART peptide induces neuroregeneration in stroke rats.
abstract: Utilizing a classic stroke model in rodents, middle cerebral artery occlusion (MCAo), we describe a novel neuroregenerative approach using the repeated intranasal administration of cocaine- and amphetamine-regulated transcript (CART) peptide starting from day 3 poststroke for enhancing the functional recovery of injured brain. Adult rats were separated into two groups with similar infarction sizes, measured by magnetic resonance imaging on day 2 after MCAo, and were treated with CART or vehicle. The CART treatment increased CART level in the brain, improved behavioral recovery, and reduced neurological scores. In the subventricular zone (SVZ), CART enhanced immunolabeling of bromodeoxyuridine, a neural progenitor cell marker Musashi-1, and the proliferating cell nuclear antigen, as well as upregulated brain-derived neurotrophic factor (BDNF) mRNA. AAV-GFP was locally applied to the SVZ to examine migration of SVZ cells. The CART enhanced migration of GFP(+) cells from SVZ toward the ischemic cortex. In SVZ culture, CART increased the size of neurospheres. The CART-mediated cell migration from SVZ explants was reduced by anti-BDNF blocking antibody. Using (1)H-MRS (proton magnetic resonance spectroscopy), increases in N-acetylaspartate levels were found in the lesioned cortex after CART treatment in stroke brain. Cocaine- and amphetamine-regulated transcript increased the expression of GAP43 and fluoro-ruby fluorescence in the lesioned cortex. In conclusion, our data suggest that intranasal CART treatment facilitates neuroregeneration in stroke brain.
authors.affiliation: National Institute on Drug Abuse, Intramural Research Program, Baltimore, Maryland 21224, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Luo
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.forename: Hua-Shan
authors.initials: HS
authors.lastname: Liu
authors.forename: Seong-Jin
authors.initials: SJ
authors.lastname: Yu
authors.forename: David J
authors.initials: DJ
authors.lastname: Reiner
authors.forename: Brandon K
authors.initials: BK
authors.lastname: Harvey
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Hoffer
authors.forename: Yihong
authors.initials: Y
authors.lastname: Yang
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis; D002465:Cell Movement / Q000187:drug effects; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D019922:GAP-43 Protein / Q000096:biosynthesis; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000633:toxicity*; D058953:Neural Stem Cells / Q000378:metabolism / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000096:biosynthesis; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D019922:GAP-43 Protein; C491296:Msi1 protein, rat; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein