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 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.
Wada
K
K
Neurotrauma Research Center and Department of Neurology, University of Miami School of Medicine, Florida 33101, USA.
Chatzipanteli
K
K
Busto
R
R
Dietrich
W D
WD
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
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