Subacute but not acute generation of nitric oxide in focal cerebral ischemia.
OBJECTIVE
Excessive release of nitric oxide (NO) has been implicated in the pathophysiology of neurodegeneration in ischemic stroke. We compared intracerebral release of indicators of NO generation at the acute and subacute stages of transient focal cerebral ischemia.


METHODS
In vivo microdialysis in the rat striatum was performed at the acute (first hours) and subacute (after 24 or 48 hours) stages of cerebral ischemia or sham operation to monitor intracerebral release of the stable NO metabolites nitrite and nitrate.


RESULTS
Whereas only a nonsignificant trend toward increased release of these NO metabolites was evidenced in acute cerebral ischemia, a significant NO generation was observed subacutely, 48 hours after induction of cerebral ischemia. Aminoguanidine, a selective inhibitor of inducible NO synthase, suppressed this delayed release of nitrite and nitrate.


CONCLUSIONS
Whereas these observations do not support a major NO generation in acute cerebral ischemia, they indicate an inducible NO synthase-dependent NO generation predominantly at the subacute phase of ischemic neurodegeneration. Therefore, NO generation may play a pathophysiological role in delayed ischemic neurodegeneration.
Fassbender
K
K
Department of Neurology, University of Heidelberg, Mannheim, Germany.
Fatar
M
M
Ragoschke
A
A
Picard
M
M
Bertsch
T
T
Kuehl
S
S
Hennerici
M
M
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D003342:Corpus Striatum / Q000378:metabolism* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D017551:Microdialysis; D009410:Nerve Degeneration / Q000209:etiology; D009566:Nitrates / Q000032:analysis; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000032:analysis; D051381:Rats; D013997:Time Factors
D004791:Enzyme Inhibitors; D006146:Guanidines; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C004479:pimagedine