Neuroprotection for ischemic stroke using hypothermia

The development of animal models of acute stroke has allowed the evaluation of mild and moderate hypothermia as a therapeutic modality in this clinical setting. Studies have demonstrated that animals subjected to hypothermia up to 3 hours after the primary central nervous system insult have reduced mortality and neuronal injury, and improved neurological outcome. These results warranted the evaluation of hypothermia in clinical trials. Even though hypothermia has potent neuroprotective effects in animal models of ischemic stroke, there are only a few clinical studies of therapeutic hypothermia in humans. Because of the small number of patients in the studies and the absence of matched controls, clinical studies are considered pilot studies for feasibility and safety. Thus, therapeutic hypothermia for ischemic stroke remains a promising but fiercely debated therapeutic modality. This review summarizes the animal model studies that have led to clinical trials in acute ischemic stroke. The existing techniques for inducing brain cooling, the mechanisms of neuroprotection, the complications of therapeutic hypothermia, and the future perspective of the field are also discussed.