Changes in oxidative stress, iNOS activity and neutrophil infiltration in severe transient focal cerebral ischemia in rats.
Oxidative stress, inducible nitric oxide synthase (iNOS) and neutrophils all contribute to post-ischemic brain damage. This study has determined the time courses of these three phenomena after ischemia in parallel with histological and functional outcomes. Ischemia was produced in rats by occluding the left middle cerebral artery and both common carotid arteries for 20 min. Regional cerebral blood flow (rCBF) rapidly decreased to 20% of its preischemic value during occlusion and stabilized at 60% following reperfusion. The striatal infarction was maximal 15 h after reperfusion (50+/-3 mm(3)), whereas the cortical infarction reached its maximum at 48 h (183+/-10 mm(3)). This drastic decrease in rCBF followed by incomplete reperfusion and massive infarction is, thus, extremely severe. The cortical infarction was strongly correlated with the neurologic deficit and loss of body weight. Oxidative stress, evaluated by the decrease in glutathione concentrations, appeared in the striatum at 6 h after reperfusion and in the cortex at 15 h. Calcium-independent NOS activity, considered as inducible NOS activity, was significantly enhanced at 24 h in the striatum and at 48 h in the cortex. Myeloperoxidase activity, a marker of neutrophil infiltration, was significantly increased at 48 h in both the striatum and cortex. These time courses show that the delayed iNOS activity and neutrophil infiltration that occur after the maturation of infarction in severe ischemia may not contribute to ischemic brain damage. By contrast, early oxidative stress may well be implicated in cerebral injury.
Lerouet
Dominique
D
Laboratoire de Pharmacologie (UPRES EA 2510), Université René Descartes, Paris, France.
Beray-Berthat
Virginie
V
Palmier
Bruno
B
Plotkine
Michel
M
Margaill
Isabelle
I
D000818:Animals; D001835:Body Weight / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D002544:Cerebral Infarction / Q000201:enzymology* / Q000276:immunology / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D004195:Disease Models, Animal; D005609:Free Radicals / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000201:enzymology / Q000276:immunology / Q000503:physiopathology; D002546:Ischemic Attack, Transient / Q000201:enzymology* / Q000276:immunology / Q000503:physiopathology; D008297:Male; D009504:Neutrophils / Q000276:immunology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D018384:Oxidative Stress / Q000276:immunology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D005609:Free Radicals; D009569:Nitric Oxide; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D005978:Glutathione; D002118:Calcium