N-acetylcysteine attenuates early induction of heme oxygenase-1 following traumatic brain injury.
Traumatic brain injury (TBI) results in a cascade of events that includes the production of reactive oxygen species. Heme oxygenase-1 (HO-1) is induced in glial cells following head trauma, suggestive of oxidative stress. We have studied the temporal and spatial effects of the antioxidant N-acetylcysteine (NAC) on HO-1 levels following lateral fluid-percussion injury by immunoblotting and immunohistochemistry. In the injured cerebral cortex, maximal HO-1 induction was seen 6 h post-TBI and was maintained for up to 24 h following the insult, while the ipsilateral hippocampus and thalamus showed marked induction at 24 h postinjury. In all three brain regions, little or no HO-1 immunoreactivity was observed on the contralateral side. Astrocytes exhibited positive immunoreactivity for HO-1 in the injured cerebral cortex, hippocampus, and thalamus, while some neurons and microglia were also immunoreactive in the injured cortex. The administration of NAC 5 min following TBI resulted in a marked reduction in this widespread induction of HO-1, concomitant with a decrease in the volume of injury in all three brain regions. Together, these findings indicate that HO-1 induction is related to both oxidative and injury characteristics of the affected tissue, suggesting that protein expression of this gene is a credible marker of oxidative damage in this model of TBI.
Yi
Jae-Hyuk
JH
Department of Medicine, Hôpital Saint-Luc (CHUM), University of Montreal, 1058 St-Denis St., Montreal, Quebec, Canada H2X 3J4.
Hazell
Alan S
AS
D000111:Acetylcysteine / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D001930:Brain Injuries / Q000188:drug therapy* / Q000201:enzymology*; D004195:Disease Models, Animal; D004790:Enzyme Induction / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing); D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D010105:Oxygenases / Q000378:metabolism*; D010474:Percussion / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D013778:Tetrazolium Salts; D013997:Time Factors
D006360:Heat-Shock Proteins; D013778:Tetrazolium Salts; C009591:triphenyltetrazolium; D010105:Oxygenases; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D000111:Acetylcysteine