title: Effects of L-NAME and 7-NI on NOS catalytic activity and behavioral outcome after traumatic brain injury in the rat.
abstract: 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.
authors: Neurotrauma Research Center and Department of Neurology, University of Miami School of Medicine, Florida 33101, USA.
authors: K
authors: K
authors: Wada
authors: K
authors: K
authors: Chatzipanteli
authors: R
authors: R
authors: Busto
authors: W D
authors: WD
authors: Dietrich
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D001930:Brain Injuries / Q000188:drug therapy* / Q000201:enzymology / Q000523:psychology; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005552:Forelimb / Q000502:physiology; D007191:Indazoles / Q000627:therapeutic use*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D010775:Photic Stimulation; D010812:Physical Stimulation; D011434:Proprioception / Q000187:drug effects / Q000502:physiology; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004791:Enzyme Inhibitors; D007191:Indazoles; D009419:Nerve Tissue Proteins; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester