Hyperbaric oxygenation reduces overexpression of c-Fos and oxidative stress in the brain stem of experimental endotoxemic rats.
OBJECTIVE
Septic encephalopathy is associated with an increased mortality rate in septic patients. We have previously shown that a peripheral lipopolysaccharide (LPS) injection induces neuronal activation in the brain-stem nuclei of rats. Nitric oxide (NO) and superoxide are involved in LPS-induced brain damage. Hyperbaric oxygenation (HBO) provides protective effects against systemic oxidative stress and mortality in animals with septic shock. We examined the effects of HBO on neuronal activation and oxidative stress in the brain-stem nuclei of LPS-treated rats.


METHODS
Wistar rats were randomly distributed into six groups for the following treatments:(a) normal saline injection (NS); (b) HBO; (c) LPS; (d) LPS-HBO; (e) LPS-aminoguanidine (AG, an inhibitor of inducible nitric oxide synthase); or (f) hydralazine (HYD, a direct vasodilator). The HYD induces prolonged hypotension and was used as a comparison for LPS stimulation. The AG was used as a comparison for HBO treatment. Two HBO sessions were administered, 1 and 4[Symbol: see text]h after LPS.


RESULTS
HBO and AG significantly reversed the overproduction of c-Fos induced by LPS in the brain stems of rats, with greater reversal in the nucleus tractus solitarii (NTS) by HBO. Although AG did not reduce the superoxide level, HBO significantly abolished superoxide production and NADPH diaphorase expression in the brain stems of LPS-treated rats. The HYD induced much lower c-Fos expression in the brain-stem nuclei than that in LPS-treated animals and caused no significant increase in NADPH diaphorase expression or superoxide formation.


CONCLUSIONS
HBO protects against endotoxin-related neuronal activation and oxidative stress in the brain-stem nuclei of rats.
Lin
Hui-Ching
HC
Department of Pharmacology, National Defense Medical Center, No. 161 Section 6 Min-Chuan East Road, 114 Taipei, Taiwan. hclin@ndmctsgh.edu.tw
Wan
Fang-Jung
FJ
D000704:Analysis of Variance; D000818:Animals; D001933:Brain Stem / Q000378:metabolism*; D006146:Guanidines / Q000494:pharmacology; D006830:Hydralazine / Q000494:pharmacology; D006931:Hyperbaric Oxygenation; D007022:Hypotension / Q000139:chemically induced / Q000188:drug therapy*; D007124:Immunoenzyme Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009249:NADP / Q000378:metabolism; D018384:Oxidative Stress; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000378:metabolism* / Q000503:physiopathology; D013481:Superoxides / Q000378:metabolism
D006146:Guanidines; D008070:Lipopolysaccharides; D016760:Proto-Oncogene Proteins c-fos; D013481:Superoxides; D006830:Hydralazine; D009249:NADP; C004479:pimagedine