Reduced matrix metalloproteinase-9 activity and cell death after global ischemia in the brain preconditioned with hyperbaric oxygen.
Matrix metalloproteinase-9 (MMP-9) plays a deleterious role in cell death after global cerebral ischemia. Preconditioning with hyperbaric oxygen (HBO-PC) reduces neuronal damage in the post-ischemic brain; however, its effect on ischemia-induced increase in MMP-9 activity and expression remains unexplored.We investigated effects of HBO-PC on alterations in MMP-9 activity/tissue expression accompanying neuronal death after transient global cerebral ischemia.Male SD rats (300-350 g), were allocated either to non-ischemic (naive control or sham-operated) or ischemic (four-vessel occlusion, 4VO; 10 min) groups that were HBO-preconditioned (2.5 ATA, 1 h daily for 5 days; the last session 24 h before ischemia) or not. Neurobehavioral deficits were assessed prior to collection of brain tissue for gel zymography (MMP-9) and histology (MMP-9 immunofluorescence, TUNEL) at 0 (without ischemia), 6, 24, 72 h and 7 days after 4VO.Both, MMP-9 levels and cell death increased in the hippocampus at 72 h after 4VO. HBO-PC suppressed postischemic MMP-9 activity and CA1 cell damage, and improved functional performance. The increase in MMP-9 immunoreactivity in the brain was also detected after HBO-PC alone. HBO-PC suppresses MMP-9 activity and expression in the postischemic hippocampus. The mechanism of HBO preconditioning may depend on the induction of MMP-9 in the preischemic phase and may be in part mediated by exhaustion of MMP-9 stores in cerebral tissues.
Ostrowski
Robert P
RP
Department of Physiology and Pharmacology, Linda University School of Medicine, Loma Linda, CA 92350, USA.
Jadhav
Vikram
V
Chen
Wanqiu
W
Zhang
John H
JH
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000201:enzymology / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology* / Q000503:physiopathology; D016923:Cell Death / Q000502:physiology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology*; D006931:Hyperbaric Oxygenation / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D020780:Matrix Metalloproteinase 9