In vivo preconditioning with normobaric hyperoxia induces ischemic tolerance partly by triggering tumor necrosis factor-alpha converting enzyme/tumor necrosis factor-alpha/nuclear factor-kappaB.
Recent studies suggest that intermittent and prolonged normobaric hyperoxia (HO) results in brain ischemic tolerance (BIT), reducing ischemic brain injury. We have attempted to determine the time course of HO-induced BIT, and to explore the putative roles of tumor necrosis factor-alpha (TNF-alpha) converting enzyme (TACE), TNF-alpha, and nuclear factor-kappaB (NF-kappaB) activation in mediating this effect. Two core experimental protocols were applied to rats (experiments 1 [E1] and 2 [E2] respectively). E1 rodents comprised six subgroups, breathing room air (RA; O(2)=21%), or 95% oxygen (HO) for 4, 8, 16 h (4RA, 8RA, 16RA and 4HO, 8HO, 16HO respectively). E2 rodents were divided into subgroups, exposed to 95% inspired HO for 4 h/day for six consecutive days (intermittent hyperoxia, InHO) or for 24 continuous hours (prolonged hyperoxia, PrHO). Each of these had a control group exposed to 21% oxygen in the same chamber. Twenty-four hours after pretreatment, each group was randomly divided to receive 60 min right middle cerebral artery occlusion (MCAO-operated), sham-operation (without MCAO), or no operation (intact). After 24 h reperfusion, neurologic deficit score (NDS), brain water content, Evans Blue extravasation (as a marker of blood-brain barrier permeability), TACE expression, serum TNF-alpha, and phosphor- kappaBalpha levels were assessed in all animals, and infarct volume in the MCAO-operated subgroups. E1: Compared with the control (RA) group, infarct volume was reduced by 58.6% and 64.4% in 16 h and 24 h respectively. NDS and Evans Blue extravasation was also reduced in 16 h and 24 h. There was no statistical difference among 4 h and 8 h. E2: Preconditioning with prolonged and intermittent HO decreased NDS, infarct volume and upregulated TACE and increased phosphor-kappaBalpha and serum TNF-alpha level significantly. Although further studies are needed to clarify the mechanisms of brain ischemic tolerance, InHO and PrHO may partly exert their effects via triggering TACE/TNF-alpha/NF-kappaB.
Bigdeli
M R
MR
Faculty of Biological Sciences, Shahid Beheshti University, Tehran, Iran. bigdelimohammadreza@yahoo.com
Khoshbaten
A
A
D051722:ADAM Proteins / Q000378:metabolism*; D000072198:ADAM17 Protein; D000818:Animals; D001812:Blood-Brain Barrier / Q000473:pathology; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D018496:Hyperoxia / Q000378:metabolism*; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism* / Q000473:pathology; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D016328:NF-kappa B / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation
D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606464:Adam17 protein, rat