title: N-Acetyl cysteine protects against injury in a rat model of focal cerebral ischemia.
abstract: Ischemic cerebrovascular disease (stroke) is one of the leading causes of death and long-time disability. Ischemia/reperfusion to any organ triggers a complex series of biochemical events, which affect the structure and function of every organelle and subcellular system of the affected cells. The purpose of this study was to investigate the therapeutic efficacy of N-acetyl cysteine (NAC), a precursor of glutathione and a potent antioxidant, to attenuate ischemia/reperfusion injury to brain tissue caused by a focal cerebral ischemia model in rats. A total of 27 male Sprague-Dawley rats weighing 250-300 g were used in this study. Focal cerebral ischemia (45 min) was induced in anesthetized rats by occluding the middle cerebral artery (MCA) with an intra-luminal suture through the internal carotid artery. The rats were scored post-reperfusion for neurological deficits. They were then sacrificed after 24 h of reperfusion and infarct volume in the brain was assessed by 2,3,5-triphenyl tetrazolium chloride (TTC). Brain sections were immunostained for tumor necrosis factor (TNF-alpha) and inducible nitric oxide synthase (iNOS). Animals treated with NAC showed a 49.7% (S.E.M.=1.25) reduction in brain infarct volume and 50% (S.E.M.=0.48) reduction in the neurological evaluation score as compared to the untreated animals. NAC treatment also blocked the ischemia/reperfusion-induced expression of tumor necrosis factor and inducible nitric oxide synthase. The data suggest that pre-administration of NAC attenuates cerebral ischemia and reperfusion injury in this brain ischemia model. This protective effect may be as a result of suppression of TNF-alpha and iNOS.
authors.affiliation: Department of Pediatrics, Division of Developmental Neurogenetics, Medical University of South Carolina, 29425, Charleston, SC, USA
authors.forename: Bipanjeet
authors.initials: B
authors.lastname: Sekhon
authors.forename: Charanpal
authors.initials: C
authors.lastname: Sekhon
authors.forename: Mushfiquddin
authors.initials: M
authors.lastname: Khan
authors.forename: Sunil J
authors.initials: SJ
authors.lastname: Patel
authors.forename: Inderjit
authors.initials: I
authors.lastname: Singh
authors.forename: Avtar K
authors.initials: AK
authors.lastname: Singh
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy*; D008297:Male; D008962:Models, Theoretical; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects
chemical_list: D016166:Free Radical Scavengers; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D000111:Acetylcysteine