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

Kojiro Wada, Katina Chatzipanteli, Raul Busto, W. Dalton Dietrich

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)203-212
Number of pages10
JournalJournal of neurotrauma
Volume16
Issue number3
DOIs
StatePublished - Mar 1999

Keywords

  • 3-bromo-7-nitro indazole
  • Behavior
  • Fluid percussion brain injury
  • Nitric oxide synthase
  • Nitro-L-arginine-methyl ester
  • Rat

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

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