Effects of brain hypothermia on brain edema formation after intracerebral hemorrhage in rats

Thrombin has been shown to play an important role in brain edema formation after intracerebral hemorrhage (ICH). The primary mechanism of thrombin-induced brain edema formation includes blood-brain barrier (BBB) disruption. Animal research suggests that moderate therapeutic hypothermia improves neurological and pathological outcome in various models of brain injuries. In this chapter, we examine the effect of brain hypothermia on brain edema formation and BBB permeability after thrombin injection into the brain in rats. Anesthetized adult rats received an injection of 10 units of thrombin into the basal ganglia. Animals were divided into the normothermic and hypothermic groups, which were housed in a room maintained at 25degreesC and in a cold room maintained at 5degreesC, respectively, for 24h. Brain water content was significantly reduced with brain hypothermia in the basal ganglia (84.3% +/- 0.6% vs 82.4% +/- 0.1%; P < 0.01). The decrease of brain water content was accompanied with a significant reduction in BBB permeability to Evans blue dye (29.4 +/- 5.3 vs 11.6 +/- 3.0 ng/g wet tissue; P < 0.05) and in accumulation of polymorphonuclear leukocytes (3.03 +/- 0.79 vs 0.27 +/- 0.16 units/g wet tissue; P < 0.05). This study indicates that brain hypothermia significantly reduces thrombin-induced brain edema formation in rats. Inhibition of thrombin-induced BBB breakdown and inflammatory response by hypothermia appear to contribute to brain protection in this model. Brain hypothermia may provide a new approach to potentially reduce ongoing edema and improve neurological outcome after severe ICH.