Abstract WP251: Neuroprotective Effect of a New Endovascular Hypothermia: Intrajugular Cooling Infusion in Experimental Ischemic Stroke

Introduction: Induction of cerebral hypothermia is a well-known therapy for ischemic stroke. However, its use is highly limited by the technical requirements. Intrajugular (IJ) cannula placement is a frequently conducted procedure in the Emergency Room. The purpose of this study was to determine the neuroprotective efficacy of IJ cold saline infusion compared to intracarotid (IC) infusion by microcatheter. Methods: Middle cerebral artery (MCA) occlusion (2 h) was achieved by an intraluminal filament in rats. Rats were randomized to 4 groups (n=56 total): sham surgery, stroke only, stroke with IC or IJ. In IC and IJ, 6 ml of isotonic 0°C saline was perfused into the right common carotid artery or internal jugular vein for over 30 minutes. The temperature of rectum, cortex and striatum was recorded for 100 min. The extent of brain injury was determined by infarct volume and neurological deficit. The BBB damage was assessed by the leakage of Evans Blue and brain edema .Expressions of apoptotic proteins (Bcl-2, Caspase-3), as well as BBB function associated molecules, including matrix metalloproteinase (MMP)-9 and aquaporin (AQP)-4 were evaluated by Western blotting. Results: The temperature of rectum, cortex, and striatum from the control group remained normal. Both IC and IJ induced a rapid drop of temperature, especially in the cortex and striatum with the lowest temperature of 34.5±0.9°C/33.5±0.8°C, or 34.6±0.7°C/33.5±0.9°C, respectively, at 40 minutes later. Both IC(35.05±0.05%) and IJ (35.56±0.07%)reduced infarct volumes compared to the control (48.08±0.04%).The neurological deficits were reduced by both IC and IJ treatment. IC reduced brain edema by 61%, while IJ by 52%. IC and IJ both significantly reduced the Evans Blue leakage as compared to control (1.04 ug/g and1.05 ug/g vs.1.11ug/g). Increased Bcl-2 and decreased caspase-3 were found in IC and IJ groups. MMP-9 and AQP-4 were also reduced by IC and IJ cooling perfusion. Conclusion: As compared to IC, IJ exerted a similar hypothermia and neuroprotection against ischemic stroke. Both IC and IJ reduced edema. Due to easy access to IJ injection, brain cooling by IJ could be developed as a promising hypothermia therapy due to its safe, quick, and effective features.