title: Inducible nitric oxide synthase expression after traumatic brain injury and neuroprotection with aminoguanidine treatment in rats.
abstract: OBJECTIVE
  We investigated the time course of inducible nitric oxide synthase (iNOS) enzymatic activity and immunocytochemical localization of iNOS expression after traumatic brain injury (TBI), as well as the possible role of iNOS in the pathogenesis of TBI.
  
  
  METHODS
  Male Sprague-Dawley rats were anesthetized and underwent moderate parasagittal fluid-percussion brain injury. Rats were decapitated 5 minutes, 6 hours, 1 day, 3 days, 7 days, or 14 days later, and iNOS enzymatic activities were measured (n = 6-8). To determine whether nitric oxide produced by iNOS contributed to the histopathological consequences of TBI, inhibition of iNOS activity using aminoguanidine (intraperitoneal injections of 100 mg/kg aminoguanidine [n = 9] or vehicle [n = 8], twice each day) was conducted for 3 days.
  
  
  RESULTS
  Significantly elevated iNOS activity was detected at 3 days (276.8+/-72.3% of contralateral value, means +/- standard errors; P < 0.05), and the most robust increase occurred 7 days after TBI (608.0+/-127.0%, P < 0.01) in the injured parietal cerebral cortex. Immunostaining for iNOS and glial fibrillary acidic protein, at 3 and 7 days after TBI, revealed that the major cellular sources of iNOS expression were cortical Layer 1 astrocytes and macrophages within the subarachnoid space. Administration of aminoguanidine did not reduce contusion volume significantly; however, treatment reduced total cortical necrotic neuron counts (1367.6+/-210.3; P < 0.01, compared with vehicle, 2808.5+/-325.1).
  
  
  CONCLUSIONS
  These data indicate that iNOS is expressed after moderate parasagittal fluid-percussion brain injury, in a time-dependent manner, and that inhibition of iNOS synthesis improves histopathological outcomes. Thus, inhibition of iNOS activation may represent a potential therapeutic strategy for the treatment of TBI.
authors.affiliation: Department of Neurology, University of Miami School of Medicine, Florida 33101, USA.
authors.forename: K
authors.initials: K
authors.lastname: Wada
authors.forename: K
authors.initials: K
authors.lastname: Chatzipanteli
authors.forename: S
authors.initials: S
authors.lastname: Kraydieh
authors.forename: R
authors.initials: R
authors.lastname: Busto
authors.forename: W D
authors.initials: WD
authors.lastname: Dietrich
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000201:enzymology; D001930:Brain Injuries / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006146:Guanidines / Q000494:pharmacology / Q000627:therapeutic use*; D008264:Macrophages / Q000201:enzymology; D008297:Male; D009336:Necrosis; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D009474:Neurons / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley; D013346:Subarachnoid Space / Q000166:cytology; D014949:Wounds, Nonpenetrating
chemical_list: D004791:Enzyme Inhibitors; D006146:Guanidines; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C004479:pimagedine