Neuronal nitric oxide synthase expression is induced in neocortical astrocytes after spreading depression.
Spreading depression (SD) confers either increased susceptibility to ischemic injury or a delayed protection. Because nitric oxide modulates ischemic injury, we investigated if altered expression of nitric oxide synthase (NOS) by SD could account for the effect of SD on ischemia. Furthermore, the identity of cells expressing NOS after SD is important, since SD results in heterogeneous, cell type-specific changes in intracellular environment, which can control NOS activity. Immunohistochemical, computer-based image analyses and Western blotting show that the number of neuronal NOS (nNOS)-positive cells in the somatosensory cortex was significantly increased at 6 hours and 3 days after SD (P < 0.05 and 0.01, respectively), whereas inducible NOS expression remained unchanged. Double-labeling of nNOS and glial fibrillary acidic protein identified these nNOS-positive cells as astrocytes. The effect of altered NO production on induced nNOS expression was examined by treating rats with sodium nitroprusside or NA-nitro-L-arginine methyl ester (LNAM) during SD. Increased nNOS expression was prevented by sodium nitroprusside and phenylephrine or phenylephrine alone, but not LNAM. Because SD increased astrocytic nNOS expression at time points correlating with both ischemic hypersensitivity and ischemic tolerance, the ability of SD to modulate ischemic injury must be complex, perhaps involving NOS but other factors as well.
Caggiano
A O
AO
Department of Neurology, University of Chicago, IL 60637, USA.
Kraig
R P
RP
D000818:Animals; D001253:Astrocytes / Q000201:enzymology / Q000502:physiology*; D013181:Cortical Spreading Depression; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D019579:Neocortex / Q000201:enzymology / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I; D051381:Rats; D017208:Rats, Wistar
D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat