title: Administration of N-acetylcysteine after focal cerebral ischemia protects brain and reduces inflammation in a rat model of experimental stroke.
abstract: Free radicals and inflammatory mediators are involved in transient focal cerebral ischemia (FCI). Preadministration of N-acetylcysteine (NAC) has been found to attenuate the cerebral ischemia-reperfusion injury in a rat model of experimental stroke. This study was undertaken to investigate the neuroprotective potential of NAC administered after ischemic events in experimental stroke. FCI was induced for 30 min by occluding the middle cerebral artery (MCA). NAC (150 mg/kg) was administered intraperitoneally at the time of reperfusion followed by another dose 6 hr later. Animals were sacrificed after 24 hr of reperfusion. The cerebral infarct consistently involved the cortex and striatum. Infarction was assessed by staining the brain sections with 2,3,5-triphenyltetrazolium chloride. Animals treated with NAC showed a significant reduction in infarct area and infarct volume and an improvement in neurologic scores and glutathione level. Reduction in infarction was significant even when a single dose of NAC was administered at 6 hr of reperfusion. Immunohistochemical and quantitative real-time PCR studies demonstrated a reduction in the expression of proinflammatory cytokines such as tumor necrosis factor alpha (TNFalpha) and interleukin 1beta (IL-1beta) and inducible nitric oxide synthase (iNOS) in NAC compared to that in vehicle-treated animals. The expression of activated macrophage/microglia (ED1) and apoptotic cell death in ischemic brain was also reduced by NAC treatment. These results indicate that in a rat model of experimental stroke, administration of NAC even after ischemia onset protected the brain from free radical injury, apoptosis, and inflammation, with a wide treatment window.
authors.affiliation: Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina 29425, USA. khanm@musc.edu
authors.forename: Mushfiquddin
authors.initials: M
authors.lastname: Khan
authors.forename: Bipanjeet
authors.initials: B
authors.lastname: Sekhon
authors.forename: Manu
authors.initials: M
authors.lastname: Jatana
authors.forename: Shailendra
authors.initials: S
authors.lastname: Giri
authors.forename: Anne G
authors.initials: AG
authors.lastname: Gilg
authors.forename: Charanpal
authors.initials: C
authors.lastname: Sekhon
authors.forename: Inderjit
authors.initials: I
authors.lastname: Singh
authors.forename: Avtar K
authors.initials: AK
authors.lastname: Singh
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use*; D000818:Animals; D002545:Brain Ischemia / Q000517:prevention & control*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D053331:Ectodysplasins; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy; D007249:Inflammation / Q000517:prevention & control; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009460:Neurologic Examination / Q000379:methods; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013778:Tetrazolium Salts; D013997:Time Factors
chemical_list: D016207:Cytokines; D053331:Ectodysplasins; D016166:Free Radical Scavengers; D005904:Glial Fibrillary Acidic Protein; D008565:Membrane Proteins; D012333:RNA, Messenger; D013778:Tetrazolium Salts; C009591:triphenyltetrazolium; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D005978:Glutathione; D000111:Acetylcysteine