Effect of hypothermia, dichloroacetate, and deferoxamine in the treatment for cortical edema and functional recovery after experimental cortical impact in the rat.

ABSTRACT

OBJECTIVE: To investigate the effects of hypothermia alone or in combination with dichloroacetic acid (DCA) and/or deferoxamine (DFO) in reducing cortical edema (CE) and improving neurologic functional recovery after moderate closed and head trauma with controlled cortical impact (CCI). METHODS: Anesthetized rats were randomized to receive right parietal moderate CCI (impact depth 2 mm, speed 3.5 m/sec) or sham operations. Immediately after trauma, the animals underwent selective brain cooling to 30 degrees C (temporalis muscle temperatures). Ten minutes after trauma, the randomized animals received intraperitoneal doses of DCA (25 mg/kg), DFO (50 mg/kg), both DCA and DFO, or equivolume normal saline. For evaluation of cortical edema, some animals (n = 42) were sacrificed 4 hours after trauma and cortical specific gravity (SpG) was determined gravimetrically. The other animals (n = 47) were evaluated for functional recovery beginning 6 days posttrauma. Neurobehavioral performance was assessed in the Morris water maze. RESULTS: Cortical edema was significantly less in the animals treated with hypothermia (SpG = 1.041 +/- 0.001, p < 0.05) compared with the untreated traumatized animals (SpG = 1.037 +/- 0.001). Combination treatment with hypothermia and drug treatment did not reduce cortical edema when compared with no treatment. Hypothermia with and without drug treatment did not improve neurobehavioral performance when compared with no treatment. CONCLUSIONS: In this pilot study with a relatively small sample size, hypothermia alone significantly reduced post-CCI cortical edema as measured by SpG. Hypothermia combined with drug treatment did not reduce posttraumatic cortical edema. Hypothermia with and without drug therapy did not improve functional neurologic recovery in the rats subjected to CCI.