The efficacy of
nitric oxide (NO) treatment in
ischemic stroke, though well recognized, is yet to be tested in clinic. NO donors used to treat ischemic injury are structurally diverse compounds. We have shown that treatment of
S-nitrosoglutathione (GSNO) protects the brain against injury and
inflammation in rats after experimental
stroke [M. Khan, B. Sekhon, S. Giri, M. Jatana, A. G. Gilg, K. Ayasolla, C. Elango, A. K. Singh, I. Singh,
S-Nitrosoglutathione reduces
inflammation and protects brain against focal
cerebral ischemia in a rat model of experimental
stroke, J. Cereb. Blood Flow Metab. 25 (2005) 177-192.]. In this study, we tested structurally different NO donors including GSNO, S-nitroso-N-acetyl-
penicillamine (SNAP),
sodium nitroprusside (SNP),
methylamine hexamethylene
methylamine NONOate (MAHMA), propylamine propylamine NONOate (PAPA), 3-morpholinosydnonimine (SIN-1) and compared their neuroprotective efficacy and
antioxidant property in rats after
ischemia/reperfusion (I/R). GSNO, in addition to neuroprotection, decreased
nitrotyrosine formation and lipid peroxidation in blood and increased the ratio of reduced versus
oxidized glutathione (GSH/
GSSG) in brain as compared to untreated animals. GSNO also prevented the I/R-induced increase in
mRNA expression of
ICAM-1 and
E-Selectin. SNAP and SNP extended limited neuroprotection, reduced
nitrotyrosine formation in blood and blocked increase in
mRNA expression of
ICAM-1 and
E-Selectin in brain tissue. PAPA, MAHMA, and SIN-1 neither protected the brain nor reduced oxidative stress. We conclude that neuroprotective action of NO donors in experimental
stroke depends on their ability to reduce oxidative stress both in brain and blood.