Effect of Brain Hypothermia on Ischemic Injury and Matrix Metalloproteinase Activity in Focal Cerebral Ischemia

ABSTRACT

BACKGROUND: Effects of hypothermia have been demonstrated in experimental animals with cerebral ischemia. Although the exact mechanisms of hypothermic effects are unknown, decrease of the blood-brain barrier (BBB) permeability, inhibition of free radical generation, and anti-inflammatory actions have been suggested. Matrix metalloproteinases (MMPs) may play a role in the hypothermic effect because they are known to mediate neuro-inflammatory responses and BBB breakdown. METHODS: The rats were subjected to 2 hours of middle cerebral artery occlusion (MCAO) and 18 hours of reperfusion. The normothermia group was maintained at 37 degrees C. Moderate hypothermia was induced by maintaining the temperature at 32 degrees C during MCAO in the intra-ischemic hypothermia (IH) group, and for 2 hours immediately after reperfusion in the postischemic hypothermia (PH) group. The infarction size in coronal slices were measured after 2, 3, 5-triphenyltetrazolium chloride stain. By gelatin zymography, the activity of MMP-2 and MMP-9 was measured. Evans blue extravasation methods were used to determine the BBB disruption. RESULTS: The infarction size was significantly decreased in the IH group compared to the normothermia group. The MMP-2 and MMP-9 activities in the ischemic hemispheres was significantly decreased in the IH group compared to the normothermia group. In the PH group, only the MMP-2 activity was significantly decreased compared to the normothermia group. Infarction size was significantly correlated with MMP-2 (r=0.688), and MMP-9 (r=0.707) activities. The disruption of BBB was significantly reduced in the IH group compared to the normothermia group. CONCLUSIONS: Intra-ischemic hypothermia effectively attenuated ischemic injury. Hypothermia-mediated inhibition of MMP-2 and MMP-9 activities may contribute to this protective effect.