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

We investigated the effects of therapeutic hypothermia (30 degrees C) on al terations in constitutive (cNOS) and inducible (iNOS) nitric oxide synthase activities following traumatic brain injury (TBI). Male Sprague-Dawley rat s were anesthetized with 0.5% halothane and underwent moderate (1.8-2.2 atm ) parasagittal fluid-percussion (F-P) brain injury. In normothermic rats (3 7 degrees 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 nitri c oxide synthase activity was significantly reduced with pretraumatic hypot hermia (138.8 +/- 17% of contralateral value; p < 0.05). At 3 and 7 days af ter normothermic TBI the enzymatic activity of cNOS was decreased significa ntly (30 +/- 8.4 and 28.6 +/- 20.9% of contralateral value, respectively; p < 0.05). However, immediate posttraumatic hypothermia (3 h at 30 degrees 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). Posttraumati c hypothermia also significantly reduced iNOS activity at 7 days compared w ith 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. Temperat ure-dependent alterations in cNOS and iNOS enzymatic activities may partici pate in the neuroprotective effect of hypothermia in this TBI model.