Mild Pre- and Posttraumatic Hypothermia Attenuates Blood-Brain Barrier Damage Following Controlled Cortical Impact Injury in the Rat

Abstract

Recent studies have demonstrated a neuroprotective effect of mild/moderate hypothermia in models of cerebral trauma and ischemia. In contrast, hypotension is known to exacerbate CNS injury. To better understand the mechanisms whereby hypothermia and hypotension influence secondary neural injury, the present study assessed the effects of these two variables upon blood-brain barrier (BBB) permeability following controlled cortical impact injury. Rats were subjected to either 0, 15, or 30 min of hypotension under normothermic or slightly hypothermic brain temperature conditions. Brain temperature was maintained within 0.5 degrees C of baseline (normothermic) or allowed to float freely (e.g., become hypothermic) throughout the study. Hypotension was induced immediately after head injury by rapid hemorrhage down to a mean arterial pressure of 50 mm Hg and held there for 15 or 30 min. Blood-brain barrier permeability was measured by the extravasation of plasma protein-bound Evan's blue dye into the injured cortex at 60 min postinjury. The results revealed that mild hypothermia (< 1.6 +/- 0.2 degrees C), right before and 15-30 min following head injury, significantly reduced BBB permeability 28.0, 21.8, and 26.2% in rats subjected to 0, 15, or 30 min hypotension, respectively (all p values < or = 0.05). Hypotension did not increase BBB permeability nor did it significantly interact with the brain temperature effect. Previous results, using this same model, have shown that the progressive posttraumatic increase in BBB permeability is preceded by an increase in cortical .OH and lipid hydroperoxides at the site of injury and is attenuated by the lipid peroxidation inhibitor tirilazad mesylate. Thus, the present results are discussed in terms of the role of free radical-induced lipid peroxidation in the genesis of posttraumatic BBB damage and the possible effects of hypothermia upon this injury process.