title: Neuroprotection of Ro25-6981 Against Ischemia/Reperfusion-Induced Brain Injury via Inhibition of Autophagy.
abstract: In this study, we investigated the neuroprotective effect of Ro25-6981 against cerebral ischemia/reperfusion injury. Ro25-6981 alone or in combination with rapamycin was intracerebroventricularly administered to rats which suffered transient forebrain ischemia inducing by 4-vessel occlusion and reperfusion. Nissl staining was used to determine the survival of CA1 pyramidal cells of the hippocampus, while immunohistochemistry was performed to measure neuron-specific enolase (NSE) expression. The expression of autophagy-related proteins, such as microtubule-associated protein l light chain 3 (LC3), Beclin 1, and sequestosome 1 (p62), was assessed by immunoblotting. Nissl staining showed that neuronal damage was reduced in the hippocampal CA1 pyramidal layer in rats that received Ro25-6981. The protective effect of Ro25-6981 was dose-dependent, with a significant effect in the middle-dose range. The expression of NSE increased after Ro25-6981 treatment. Ro25-6981 significantly decreased LC3II (which is membrane bound) and Beclin 1, and increased p62. In addition, Ro25-6981 decreased rapamycin-induced neuronal damage and excessive activation of autophagy after I/R. Taken together, the results suggest that Ro25-6981 could suppress ischemic brain injury by regulating autophagy-related proteins during ischemia/reperfusion.
authors.affiliation: Research Center for Neurobiology, Xuzhou Medical University, No. 209, Tongshan Road, Yunlong District, Xuzhou, 221004, Jiangsu, People's Republic of China.
authors.forename: Fuxing
authors.initials: F
authors.lastname: Dong
authors.affiliation: Research Center for Neurobiology, Xuzhou Medical University, No. 209, Tongshan Road, Yunlong District, Xuzhou, 221004, Jiangsu, People's Republic of China.
authors.forename: Ruiqin
authors.initials: R
authors.lastname: Yao
authors.affiliation: Research Center for Neurobiology, Xuzhou Medical University, No. 209, Tongshan Road, Yunlong District, Xuzhou, 221004, Jiangsu, People's Republic of China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Yu
authors.affiliation: Laboratory of National Experimental Teaching and Demonstration Center of Basic Medicine, Xuzhou Medical University, No. 209, Tongshan Road, Yunlong District, Xuzhou, 221004, Jiangsu, People's Republic of China. ya-ping-liu@163.com.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D001921:Brain / Q000378:metabolism; D001930:Brain Injuries / Q000188:drug therapy*; D002545:Brain Ischemia / Q000188:drug therapy; D004195:Disease Models, Animal; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D000066829:Neuroprotection / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010636:Phenols / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000517:prevention & control
chemical_list: D051017:Apoptosis Regulatory Proteins; D008869:Microtubule-Associated Proteins; D018696:Neuroprotective Agents; D010636:Phenols; D010880:Piperidines; C109643:Ro 25-6981
keywords: Autophagy; Ischemia/reperfusion; N-methyl-D-aspartate receptor; Ro25-6981