Intravenous recombinant
tissue plasminogen activator remains the only US FDA-approved treatment for
acute ischemic stroke. However, the very limited time window for its administration restricts its usefulness. Furthermore, it is becoming increasingly clear that, given the numerous pathways via which
cerebral ischemia causes cell death, the capacity to inhibit multiple mechanisms simultaneously may provide additive or synergistic beneficial clinical effects for
stroke patients. Although no clinical trials have yet investigated the efficacy of
therapeutic hypothermia in focal
cerebral ischemia, its pleiotropic neuroprotective actions, positive results in preclinical studies, as well as proven enhancement of neurologic outcomes in survivors of
cardiac arrest and newborns with
hypoxic-ischemic encephalopathy, make this neuroprotective strategy highly promising. This review presents an overview of the potential role of
hypothermia in the treatment of
acute ischemic stroke and discusses ischemic cell death pathophysiology, neuroprotective mechanisms of
hypothermia, methodologies employed for the induction of
hypothermia, results from animal models of
cerebral ischemia, and finally, currently available clinical trial data. Two valuable lessons learned thus far are that first, rapid induction of
hypothermia is key and is best accomplished with a combination of
ice-cold saline infusion and the use of endovascular cooling devices, and second, that shivering can be overcome with aggressive anti-shivering protocols including
meperidine,
buspirone and surface warming. We await the results of clinical trials to determine the utility of
therapeutic hypothermia in
acute ischemic stroke. If proven efficacious,
hypothermia would be a welcome
complement to established reperfusion
therapies for
ischemic stroke patients.