Effects of L-NAME and 7-NI on NOS catalytic activity and behavioral outcome after traumatic brain injury in the rat

Traumatic brain injury (TBI) produces transient increases in constitutive n itric oxide synthase (cNOS) activity and prolonged behavioral abnormalities . This study investigated the effects of nitro-L-arginine-methyl ester (L-N AME) and 3-bromo-7-nitroindazole (7-NI) treatment on cNOS catalytic activit y and sensorimotor behavioral outcome after TBI, Rats underwent moderate (1 .8-2.2 atm) parasagittal fluid percussion brain injury (FPI). At 5 min afte r FPI, cNOS activity was significantly increased within the damaged cerebra l cortex of vehicle-treated rats compared to the noninjured contralateral c ortex (206.7 +/- 150.5% of contralateral,p < 0.01). Pretreatment with L-NAM E and 7-NI significantly reduced injury-induced cNOS activation (47.7 +/- 4 2.6%,p < 0.05, and 96.16 +/- 12.76, p < 0.05, respectively). Pretreatment w ith L-NAME and 7-NI also inhibited cNOS activity within the contralateral n oninjured cerebral cortex compared to vehicle-treated rats (L-NAME 43.7 +/- 12.47%,p < 0.05; 7-NI 36.8 +/- 7.47%,p < 0.05), Furthermore, pretreatment with 7-NI, but not L-NAME, significantly reduced forelimb placing sensorimo tor deficits (3.14 +/- 1.07, p < 0.05) at 1 day after TBI compared to vehic le-treated rats (5.38 +/- 0.42), These data indicate that inhibition of inj ury-induced elevations in neuronal NOS activity has a beneficial effect on neurological outcome after parasagittal FPI brain injury.