TY - JOUR
T1 - Effects of moderate hypothermia on constitutive and inducible nitric oxide synthase activities after traumatic brain injury in the rat
AU - Chatzipanteli, Katina
AU - Wada, Kojiro
AU - Busto, Raul
AU - Dietrich, W. Dalton
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
KW - Constitutive nitric oxide synthase
KW - Fluid-percussion brain injury
KW - Hypothermia
KW - Inducible nitric oxide synthase
KW - Nitric oxide
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U2 - 10.1046/j.1471-4159.1999.0722047.x
DO - 10.1046/j.1471-4159.1999.0722047.x
M3 - Article
C2 - 10217283
AN - SCOPUS:0032971460
VL - 72
SP - 2047
EP - 2052
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 5
ER -