Hypothermia for Acute Ischemic Stroke: Not Just Another Neuroprotectant

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Abstract
Based on empirical experience, hypothermia has long been known to be a potent putative neuroprotectant. Recent insights into the mechanisms of central ischemia and reperfusion suggest reasons why hypothermia may be an ideal modality for extending the time window for thrombolytic stroke therapy. Hypothermia protects brain tissue from the effects of ischemia in multiple ways. It retards energy depletion, reduces intracellular acidosis, and lessens the ischemic overdose of excitatory neurotransmitters. This attenuates the influx of intracellular calcium, the herald of subsequent neuronal death. Additionally, hypothermia suppresses synthesis of oxygen free radicals involved in secondary damage associated with reperfusion. It also suppresses the mechanisms related to blood-brain barrier degeneration and post-ischemic remodeling. Animal and human data show that deep hypothermia is primarily protective and is used in several cardiothoracic and neurosurgical applications, and that mild hypothermia enhances recovery after focal and global ischemic brain injuries. Preliminary data on hypothermia in human stroke also show promising potential. Current methods of instituting hypothermia, including patient selection, temperature and timing, cooling methods, and complications are reviewed in detail. Neuroprotection conferred by mild to moderate hypothermia is likely to undergo phase III clinical trials in various clinical settings. Novel technology promises a broad application even outside intensive care settings. Preliminary studies suggest that mild to moderate hypothermia is a useful adjunct to thrombolytic therapy for stroke. Timing, degree, and duration rules are being developed and methods of cooling further perfected to optimize the safety and efficacy of this promising approach.