MODULATION OF ISCHEMIC EXCITATORY NEUROTRANSMITTER AND GAMMA-AMINOBUTYRIC-ACID RELEASE DURING GLOBAL TEMPORARY CEREBRAL-ISCHEMIA BY LOCAL NITRIC-OXIDE SYNTHASE INHIBITION

Systemic nitric oxide synthase inhibition (NOSI) decreases cerebral bl ood flow, which may worsen ischemic insults. To examine the local effe cts of NOSI without this confounding effect, we examined the role of a locally administered NOSI, N-G-nitro-L-arginine-methyl-ester (L-NAME) , on neurotransmitter recovery during cerebral ischemia. Rats were ass igned to one of three groups: locally administered L-NAME via a striat al microdialysis probe (n = 11), systemic L-NAME (n = 5), or control ( n = 11). Temporary global forebrain ischemia was induced for 15 min, f ollowed by 60 min of reperfusion. L-NAME resulted in decreases of basa l aspartate (ASP; 74% of basal) and glutamate (GLU; 60% of basal) reco very. While systemic L-NAME caused significant increases in ischemic A SP and GLU recovery (by 224% and 110%, respectively, compared with isc hemic controls), local NOSI administration resulted in a significant a ttenuation of peak ASP, GLU, glycine, and gamma-aminobutyric acid reco very (43%, 38%, 53%, and 72%, respectively, compared with ischemic con trols). We conclude that local NOSI attenuated ischemic neurotransmitt er recovery during ischemia/reperfusion. Our results emphasize the imp ortance of the systemic effects of NOSI and suggest both deleterious a nd beneficial effects of NOSI during ischemia/reperfusion.