PMID- 23211962 OWN - NLM STAT- MEDLINE DCOM- 20130325 LR - 20211021 IS - 1559-7016 (Electronic) IS - 0271-678X (Print) IS - 0271-678X (Linking) VI - 33 IP - 2 DP - 2013 Feb TI - CART peptide induces neuroregeneration in stroke rats. PG - 300-10 LID - 10.1038/jcbfm.2012.172 [doi] AB - 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. FAU - Luo, Yu AU - Luo Y AD - National Institute on Drug Abuse, Intramural Research Program, Baltimore, Maryland 21224, USA. FAU - Shen, Hui AU - Shen H FAU - Liu, Hua-Shan AU - Liu HS FAU - Yu, Seong-Jin AU - Yu SJ FAU - Reiner, David J AU - Reiner DJ FAU - Harvey, Brandon K AU - Harvey BK FAU - Hoffer, Barry J AU - Hoffer BJ FAU - Yang, Yihong AU - Yang Y FAU - Wang, Yun AU - Wang Y LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20121205 PL - United States TA - J Cereb Blood Flow Metab JT - Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism JID - 8112566 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (GAP-43 Protein) RN - 0 (Msi1 protein, rat) RN - 0 (Nerve Tissue Proteins) RN - 0 (RNA, Messenger) RN - 0 (RNA-Binding Proteins) RN - 0 (cocaine- and amphetamine-regulated transcript protein) SB - IM MH - Administration, Intranasal MH - Animals MH - Behavior, Animal/drug effects MH - Brain-Derived Neurotrophic Factor/biosynthesis MH - Cell Movement/drug effects MH - Cerebral Cortex/metabolism/pathology/physiopathology MH - Disease Models, Animal MH - GAP-43 Protein/biosynthesis MH - Male MH - Nerve Tissue Proteins/metabolism/*toxicity MH - Neural Stem Cells/metabolism/pathology MH - Neurodegenerative Diseases/chemically induced/*metabolism/pathology/physiopathology MH - RNA, Messenger/biosynthesis MH - RNA-Binding Proteins/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Stroke/complications/*metabolism/pathology/physiopathology MH - Time Factors MH - Up-Regulation/drug effects PMC - PMC3564201 EDAT- 2012/12/06 06:00 MHDA- 2013/03/26 06:00 PMCR- 2013/02/01 CRDT- 2012/12/06 06:00 PHST- 2012/12/06 06:00 [entrez] PHST- 2012/12/06 06:00 [pubmed] PHST- 2013/03/26 06:00 [medline] PHST- 2013/02/01 00:00 [pmc-release] AID - jcbfm2012172 [pii] AID - 10.1038/jcbfm.2012.172 [doi] PST - ppublish SO - J Cereb Blood Flow Metab. 2013 Feb;33(2):300-10. doi: 10.1038/jcbfm.2012.172. Epub 2012 Dec 5.