Role of nitric oxide in traumatic brain injury in the rat

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

Research output: Contribution to journalArticle

146 Citations (Scopus)

Abstract

Object. Although nitric oxide (NO) has been shown to play an important role in the pathophysiological process of cerebral ischemia, its contribution to the pathogenesis of traumatic brain injury (TBI) remains to be clarified. The authors investigated alterations in constitutive nitric oxide synthase (NOS) activity after TBI and the histopathological response to pharmacological manipulations of NO. Methods. Male Sprague-Dawley rats underwent moderate (1.7-2.2 atm) parasagittal fluid-percussion brain injury. Constitutive NOS activity significantly increased within the ipsilateral parietal cerebral cortex, which is the site of histopathological vulnerability, 5 minutes after TBI occurred (234.5 ± 60.2% of contralateral value [mean ± standard error of the mean {SEM}], p < 0.05), returned to control values by 30 minutes (114.1 ± 17.4%), and was reduced at 1 day after TBI (50.5 ± 13.1%, p < 0 01) The reduction in constitutive NOS activity remained for up to 7 days after TBI (31.8 ± 6.0% at 3 days, p < 0.05; 20.1 ± 12.7% at 7 days, p < 0.01). Pretreatment with 3-bromo-7-nitroindazole (7- NI) (25 mg/kg), a relatively specific inhibitor of neuronal NOS, significantly decreased contusion volume (1.27 ± 0.17 mm3 [mean ± SEMI, p < 0.05) compared with that of control (2.52 ± 0.35 mm3). However, posttreatment with 7-NI or pre-or posttreatment with nitro-L-arginine-methyl ester (L-NAME) (15 mg/kg), a nonspecific inhibitor of NOS, did not affect the contusion volume compared with that of control animals (1.87 ± 0.46 mm3, 2.13 ± 0.43 mm3, and 2.18 ± 0.53 mm3, respectively). Posttreatment with L-arginine (1.1 ± 0.3 mm3, p < 0.05), but not 3-morpholino-sydnonimine (SIN-1) (2.48 ± 0.37 mm3), significantly reduced the contusion volume compared with that of control animals. Conclusions. These data indicate that constitutive NOS activity is affected after moderate parasagittal fluid percussion brain injury in a time-dependent manner. Inhibition of activated neuronal NOS and/or enhanced endothelial NOS activation may represent a potential therapeutic strategy for the treatment of TBI.

Original languageEnglish
Pages (from-to)807-818
Number of pages12
JournalJournal of Neurosurgery
Volume89
Issue number5
StatePublished - Nov 1 1998

Fingerprint

Nitric Oxide
Nitric Oxide Synthase
Contusions
Percussion
Nitric Oxide Synthase Type I
Brain Injuries
Parietal Lobe
Nitric Oxide Synthase Type III
NG-Nitroarginine Methyl Ester
Brain Ischemia
Cerebral Cortex
Sprague Dawley Rats
Arginine
Traumatic Brain Injury
Pharmacology
Therapeutics

Keywords

  • Fluid-percussion brain injury
  • L- arginine
  • Nitric oxide
  • Nitric oxide inhibitor
  • Nitric oxide synthase
  • Rat

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Role of nitric oxide in traumatic brain injury in the rat. / Wada, Kojiro; Chatzipanteli, Katina; Busto, Raul; Dalton Dietrich, W.

In: Journal of Neurosurgery, Vol. 89, No. 5, 01.11.1998, p. 807-818.

Research output: Contribution to journalArticle

Wada, K, Chatzipanteli, K, Busto, R & Dalton Dietrich, W 1998, 'Role of nitric oxide in traumatic brain injury in the rat', Journal of Neurosurgery, vol. 89, no. 5, pp. 807-818.
Wada, Kojiro ; Chatzipanteli, Katina ; Busto, Raul ; Dalton Dietrich, W. / Role of nitric oxide in traumatic brain injury in the rat. In: Journal of Neurosurgery. 1998 ; Vol. 89, No. 5. pp. 807-818.
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N2 - Object. Although nitric oxide (NO) has been shown to play an important role in the pathophysiological process of cerebral ischemia, its contribution to the pathogenesis of traumatic brain injury (TBI) remains to be clarified. The authors investigated alterations in constitutive nitric oxide synthase (NOS) activity after TBI and the histopathological response to pharmacological manipulations of NO. Methods. Male Sprague-Dawley rats underwent moderate (1.7-2.2 atm) parasagittal fluid-percussion brain injury. Constitutive NOS activity significantly increased within the ipsilateral parietal cerebral cortex, which is the site of histopathological vulnerability, 5 minutes after TBI occurred (234.5 ± 60.2% of contralateral value [mean ± standard error of the mean {SEM}], p < 0.05), returned to control values by 30 minutes (114.1 ± 17.4%), and was reduced at 1 day after TBI (50.5 ± 13.1%, p < 0 01) The reduction in constitutive NOS activity remained for up to 7 days after TBI (31.8 ± 6.0% at 3 days, p < 0.05; 20.1 ± 12.7% at 7 days, p < 0.01). Pretreatment with 3-bromo-7-nitroindazole (7- NI) (25 mg/kg), a relatively specific inhibitor of neuronal NOS, significantly decreased contusion volume (1.27 ± 0.17 mm3 [mean ± SEMI, p < 0.05) compared with that of control (2.52 ± 0.35 mm3). However, posttreatment with 7-NI or pre-or posttreatment with nitro-L-arginine-methyl ester (L-NAME) (15 mg/kg), a nonspecific inhibitor of NOS, did not affect the contusion volume compared with that of control animals (1.87 ± 0.46 mm3, 2.13 ± 0.43 mm3, and 2.18 ± 0.53 mm3, respectively). Posttreatment with L-arginine (1.1 ± 0.3 mm3, p < 0.05), but not 3-morpholino-sydnonimine (SIN-1) (2.48 ± 0.37 mm3), significantly reduced the contusion volume compared with that of control animals. Conclusions. These data indicate that constitutive NOS activity is affected after moderate parasagittal fluid percussion brain injury in a time-dependent manner. Inhibition of activated neuronal NOS and/or enhanced endothelial NOS activation may represent a potential therapeutic strategy for the treatment of TBI.

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