Long-term neuroprotection induced by regional brain cooling with saline infusion into ischemic territory in rats: a behavioral analysis

Abstract

The neuroprotective effect of hypothermia has long been recognized. Our recent studies have demonstrated the significant therapeutic value of local brain cooling in the ischemic territory prior to reperfusion in stroke, with reduced infarction and inflammatory responses up to 48 hours of reperfusion. The goal of this study was to determine if local brain cooling, produced by infusion of cold saline, could induce long-term functional improvement after stroke. 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°C) for 10 minutes prior to reperfusion. This brain cooling infusion induced a significant (p < 0.01) decrease in neurologic deficits and significantly (p < 0.01) improved motor behavior in ischemic rats after 14 days of reperfusion, compared with ischemic rats without local cold saline infusion. This improvement continued for up to 28 days after reperfusion. No significant difference in motor performance was observed between the brain cooling infusion and normal control groups. Significant (p < 0.01) reductions in infarct volume were also evident. In conclusion, a local cerebral hypothermia induced by local saline infusion prior to reperfusion produced a long-term functional recovery after ischemic stroke. A therapeutic procedure, which combines prereperfusion infusion into an ischemic region with coincident cerebral hypothermia and perhaps subsequent recanalization of an occluded intracranial vessel, may improve the outcome for stroke patients.