Abstract
Background: Therapeutic hypothermia as a neuroprotective strategy after stroke has been well established in animal models, but its application in humans has been limited by logistical challenges. To provide a solution to these challenges, this study was designed to determine the hypothermic and neuroprotective efficacy of infusing cold saline directly into the internal jugular (IJ) vein, and compare the effects of IJ regional cerebral hypothermia to those achieved by intra-carotid (IC) artery regional hypothermia in an ischemic stroke model. Methods: Middle cerebral artery occlusion was established in rats using an intraluminal filament. Regional cerebral hypothermia was then achieved by infusion of 6 ml of 0 °C isotonic saline by micro-catheter into the right IJ or right IC for 30 minutes immediately after the initiation of reperfusion. Infarct sizes, neurological deficits, edema volume, blood brain barrier (BBB) damage, BBB associated molecules (MMP-9 and AQP-4), and apoptosis associated proteins (Bcl-2 and cleaved Caspase-3) were measured. Results: Both IJ and IC infusion led to a significant, rapid reduction in brain temperatures while having a minimal effect on rectal temperatures. Infarct sizes were significantly reduced at 24 hours after reperfusion by IC and IJ treatments. Neurologic deficits were also significantly improved by IC and IJ infusion compared to control models over a 28-day observation period. Both IC and IJ significantly reduced Evans Blue leakage and edema volume compared with control groups. MMP-9 and AQP-4 expression were also reduced, Bcl-2 increased, and cleaved Caspase-3 decreased in the IC and IJ groups. Conclusion: Compared to IC infusion, IJ infusion conferred a similar degree of regional cerebral hypothermia and neuroprotection following ischemic stroke. Given the ease of establishing vascular access via the internal jugular vein and the powerful neuroprotection that hypothermia provides, IJ regional brain cooling could be utilized as a promising hypothermia-induction modality due to its safe, quick, and effective features.
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