Effects of moderate hypothermia on constitutive and inducible nitric oxide synthase activities after traumatic brain injury in the rat

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

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

We investigated the effects of therapeutic hypothermia (30°C) on alterations n constitutive (cNOS) and inducible (iNOS) nitric oxide synthase activities following traumatic brain injury (TBI). Male Sprague-Dawley rats were anesthetized with 0.5% halothane and underwent moderate (1.8-2.2 atm) parasagittal fluid-percussion (F-P) brain injury. In normothermic rats (37°C) the enzymatic activity of cNOS was significantly increased at 5 min within the injured cerebral cortex compared with contralateral values (286.5 ± 68.9% of contralateral value; mean ± SEM). This rise in nitric oxide synthase activity was significantly reduced with pretraumatic hypothermia (138.8 ± 17% of contralateral value; p < 0.05). At 3 and 7 days after normothermic TBI the enzymatic activity of cNOS was decreased significantly (30 ± 8.4 and 28.6 ± 20.9% of contralateral value, respectively; p < 0.05). However, immediate posttraumatic hypothermia (3 h at 30°C) preserved cNOS activity at 3 and 7 days (69.5 ± 23.3 and 78.6 ± 7.6% of contralateral value, respectively; mean ± SEM; p < 0.05). Posttraumatic hypothermia also significantly reduced iNOS activity at 7 days compared with normothermic rats (0.021 ± 0.06 and 0.23 ± 0.06 pmol/mg of protein/min, respectively; p < 0.05). The present results indicate that hypothermia (a) decreases early cNOS activation after TBI, (b) preserves cNOS activity at later periods, and (c) prevents the delayed induction of iNOS. Temperature-dependent alterations in cNOS and iNOS enzymatic activities may participate in the neuroprotective effect of hypothermia in this TBI model.

Original languageEnglish (US)
Pages (from-to)2047-2052
Number of pages6
JournalJournal of neurochemistry
Volume72
Issue number5
DOIs
StatePublished - Apr 28 1999

Keywords

  • Constitutive nitric oxide synthase
  • Fluid-percussion brain injury
  • Hypothermia
  • Inducible nitric oxide synthase
  • Nitric oxide

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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