Traumatic brain injury (TBI) produces transient increases in constitutive nitric oxide synthase (cNOS) activity and prolonged behavioral abnormalities. This study investigated the effects of nitro-l-arginine-methyl ester (l-NAME) and 3-bromo-7-nitroindazole (7-NI) treatment on cNOS catalytic activity and sensorimotor behavioral outcome after TBI. Rats underwent moderate (1.8–2.2 atm) parasagittal fluid percussion brain injury (FPI). At 5 min after FPI, cNOS activity was significantly increased within the damaged cerebral cortex of vehicle-treated rats compared to the noninjured contralateral cortex (206.7 ± 150.5% of contralateral,p < 0.01). Pretreatment with l-NAME and 7-NI significantly reduced injury-induced cNOS activation (47.7 ± 42.6%,p < 0.05, and 96.16 ± 12.76, p < 0.05, respectively). Pretreatment with l-NAME and 7-NI also inhibited cNOS activity within the contralateral noninjured 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 sensorimotor deficits (3.14 ± 1.07, p < 0.05) at 1 day after TBI compared to vehicle-treated rats (5.38 ± 0.42). These data indicate that inhibition of injury-induced elevations in neuronal NOS activity has a beneficial effect on neurological outcome after parasagittal FPI brain injury.
