Regional brain cooling induced by vascular saline infusion into ischemic territory reduces brain inflammation in stroke

Abstract

The neuroprotective effect of hypothermia has long been recognized. Use of hypothermia for stroke therapy, which is currently being induced by whole body surface cooling, has been largely limited because of management problems and severe side effects (i.e., pneumonia). Our recent studies have demonstrated the significant therapeutic value of local brain cooling in the ischemic territory prior to reperfusion in stroke. The goal of this study was to determine if cerebral local cooling infusion could reduce stroke-mediated brain injury by inhibiting inflammatory responses. A hollow filament was used to block the middle cerebral artery (MCA) for 3 hours, and then to locally infuse the ischemic territory with 6 ml cold saline (20 degrees C) for 10 min prior to 48-h reperfusion. This cold saline infusion significantly ( P<0.01) reduced temperature of the MCA supplied territory (in cerebral cortex from 37.2+/-0.1 degrees C to 33.4+/-0.4 degrees C, in striatum from 37.5+/-0.2 degrees C to 33.9+/-0.4 degrees C), with the hypothermia remaining for at least 45 min after reperfusion. Consequently, significant ( P<0.01) reductions in endothelial expression of intracellular adhesion molecule-1 (ICAM-1), the key step for inflammatory progress, as well as leukocyte infiltration, were evident in both cortex and striatum after reperfusion. As a control, ischemic rats received the same amount of cold saline systemically through a femoral artery. A mild hypothermia was induced in the cerebral cortex (35.3+/-0.2 degrees C) but not in the striatum (36.8+/-0.2 degrees C). The reduced cortical temperature returned to normal within 5 min. Brain temperature in ischemic rats perfused locally with saline at 37 degrees C remained normal. Intensive expression of ICAM-1 and accumulation of leukocytes was observed in ischemic control groups without brain cooling infusion. In conclusion, brain hypothermia induced by local pre-reperfusion infusion ameliorated brain inflammation from stroke.