title: Chronic nicotine exposure exacerbates transient focal cerebral ischemia-induced brain injury.
abstract: Tobacco smoking is a risk factor contributing to the development and progression of ischemic stroke. Among many chemicals in tobacco, nicotine may be a key contributor. We hypothesized that nicotine alters the balance between oxidant and antioxidant networks leading to an increase in brain injury following transient focal cerebral ischemia. Male Sprague-Dawley were treated with nicotine (2 or 4 mg·kg(-1)·day(-1)) for 4 wk via an implanted subcutaneous osmotic minipump and subjected to a 2-h middle cerebral artery occlusion (MCAO). Infarct size and neurological deficits were evaluated at 24 h of reperfusion. Superoxide levels were determined by lucigenin-enhanced chemiluminescence. Expression of oxidant and antioxidant proteins was measured using Western blot analysis. We found that chronic nicotine exposure significantly increased infarct size and worsened neurological deficits. In addition, nicotine significantly elevated superoxide levels of cerebral cortex under basal conditions. Transient focal cerebral ischemia produced an increase in superoxide levels of cerebral cortex in control group, but no further increase was found in the nicotine group. Furthermore, chronic nicotine exposure did not alter protein expression of NADPH oxidase but significantly decreased MnSOD and uncoupling protein-2 (UCP-2) in the cerebral cortex and cerebral arteries. Our findings suggest that nicotine-induced exacerbation in brain damage following transient focal cerebral ischemia may be related to a preexisting oxidative stress via decreasing of MnSOD and UCP-2.
authors.affiliation: Department of Cellular Biology and Anatomy, Center for Cardiovascular Diseases and Sciences, Louisiana State University Health Sciences Center-Shreveport, Shreveport, Louisiana.
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Cellular Biology and Anatomy, Center for Cardiovascular Diseases and Sciences, Louisiana State University Health Sciences Center-Shreveport, Shreveport, Louisiana.
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Cellular Biology and Anatomy, Center for Cardiovascular Diseases and Sciences, Louisiana State University Health Sciences Center-Shreveport, Shreveport, Louisiana.
authors.forename: Denise M
authors.initials: DM
authors.lastname: Arrick
authors.affiliation: Department of Cellular Biology and Anatomy, Center for Cardiovascular Diseases and Sciences, Louisiana State University Health Sciences Center-Shreveport, Shreveport, Louisiana wmayha@lsuhsc.edu.
authors.forename: William G
authors.initials: WG
authors.lastname: Mayhan
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001930:Brain Injuries / Q000378:metabolism / Q000503:physiopathology*; D002536:Cerebral Arteries / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000503:physiopathology; D007473:Ion Channels / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D024101:Mitochondrial Proteins / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D009538:Nicotine / Q000009:adverse effects*; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology*; D020521:Stroke / Q000378:metabolism / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D000071246:Uncoupling Protein 2
chemical_list: D000975:Antioxidants; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; D013481:Superoxides; D009538:Nicotine; D013482:Superoxide Dismutase; D019255:NADPH Oxidases
keywords: MnSOD; UCP-2; ischemia; nicotine; oxidative stress; reperfusion