Abstract WP146: DHC Enhances the Hypothermia-induced Neuroprotection Following Ischemic Stroke in Rat Over a Long-term Period

Abstract

Introduction: The combination of pharmacological hypothermia and intra-arterial selective cold infusions (SCI) was found to enhance the efficiency of hypothermia and efficacy of hypothermia-induced neuroprotection in acute ischemic stroke of rats. The aim of this study was to explore whether the combination could induce a long-term neuroprotective effects, as well as the underlying mechanism. Methods: Sprague-Dawley rats were subjected to right middle cerebral artery occlusion (MCAO) for 2 h using intraluminal hollow filament. The ischemic rats were randomized to receive: 1) pharmacological hypothermia by intraperitoneal (i.p.) injection of dihydrocapsaicin (DHC); 2) physical hypothermia by SCI for 10 min; or 3) the combined treatments. Extent of brain injury was determined by neurological deficit, infarct volume over a 21-day observation period. BBB permeability was assessed by detecting EB contents in ischemic hemispheric tissue at 2 h. Cytokine factors were determined in both infarct and penumbra areas in a quantitative way at 24 h after the onset of ischemia. Results: MRI-based infarct size analysis indicated that the combination of DHC and SCI resulted in a further reduction in infarct volume at both 48 h and 21 day following the onset of ischemia than either alone (P<0.05). Furthermore, the combination treatment favorably improved neurologic deficit scores over the 21-day observation period (P<0.01 or 0.05). This neuroprotective effects could partially be ascribed to decreased blood brain barrier injury, reduced pro-inflammatory cytokines (TNF-α, IL-2, and IFN-γ) in the infarct areas and/or penumbra areas, and increased protective cytokines (IL-4 and IL-10) in the infarct and/or penumbra regions. Conclusions: The combination approach was able to enhance the efficacy of hypothermia-induced neuroprotection following ischemic stroke in a long-term. The findings here provide a hint to translate the combination method from bench to bedside.