title: 1400W ameliorates acute hypobaric hypoxia/reoxygenation-induced cognitive deficits by suppressing the induction of inducible nitric oxide synthase in rat cerebral cortex microglia.
abstract: Nitric oxide (NO) is involved in neuronal modifications, and overproduction of NO contributes to memory deficits after acute hypobaric hypoxia-reoxygenation. This study investigated the ability of the iNOS inhibitor 1400W to counteract spatial memory deficits following acute hypobaric hypoxia-reoxygenation, and to affect expression of NOS, NO, 3-NT and MDA production, and apoptosis in rat cerebral cortex. We also used primary rat microglia to investigate the effect of 1400W on expression of NOS, NO, 3-NT and MDA production, and apoptosis. Acute hypobaric hypoxia-reoxygenation impaired spatial memory, and was accompanied by activated microglia, increased iNOS expression, NO, 3-NT and MDA production, and neuronal cell apoptosis in rat cerebral cortex one day post-reoxygenation. 1400W treatment inhibited iNOS expression without affecting nNOS or eNOS. 1400W also reduced NO, 3-NT and MDA production, and prevented neuronal cell apoptosis in cerebral cortex, in addition to reversing spatial memory impairment after acute hypobaric hypoxia-reoxygenation. Hypoxia-reoxygenation activated primary microglia, and increased iNOS and nNOS expression, NO, 3-NT, and MDA production, and apoptosis. Treatment with 1400W inhibited iNOS expression without affecting nNOS, reduced NO, 3-NT and MDA production, and prevented apoptosis in primary microglia. Based on the above findings, we concluded that the highly selective iNOS inhibitor 1400W inhibited iNOS induction in microglial cells, and reduced generation of NO, thereby mitigating oxidative stress and neuronal cell apoptosis in the rat cerebral cortex, and improving the spatial memory dysfunction caused by acute hypobaric hypoxia-reoxygenation.
authors.affiliation: Medical Research Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China; Clinical Laboratory Diagnostic Center, General Hospital of Xinjiang Military Region, Urumqi 830000, Xinjiang, China.
authors.forename: Qinghai
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Medical Research Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Medical Research Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: Medical Research Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Xinchuan
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Clinical Laboratory Diagnostic Center, General Hospital of Xinjiang Military Region, Urumqi 830000, Xinjiang, China.
authors.forename: Jihua
authors.initials: J
authors.lastname: Ran
authors.affiliation: Clinical Laboratory Diagnostic Center, General Hospital of Xinjiang Military Region, Urumqi 830000, Xinjiang, China.
authors.forename: Zhengxiang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Clinical Laboratory Diagnostic Center, General Hospital of Xinjiang Military Region, Urumqi 830000, Xinjiang, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Fu
authors.affiliation: Medical Research Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. Electronic address: zhengj99219@163.com.
authors.forename: Jiang
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D000860:Hypoxia / Q000150:complications; D007097:Imines / Q000494:pharmacology* / Q000627:therapeutic use*; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D017628:Microglia / Q000201:enzymology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D010100:Oxygen / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D017304:Annexin A5; D007097:Imines; C496401:N-((3-(aminomethyl)phenyl)methyl)ethanimidamide; D009419:Nerve Tissue Proteins; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde; D052247:Nitric Oxide Synthase Type II; D010100:Oxygen
keywords: Hypobaric; Hypoxia; Inducible nitric oxide synthase; Nitric oxide; Reoxygenation; Spatial memory