Therapeutic hypothermia for acute stroke.
Hypothermia is the most potent neuroprotective therapy available. Clinical use of hypothermia is limited by technology and homeostatic mechanisms that maintain core body temperature. Recent advances in intravascular cooling catheters and successful trials of hypothermia for cardiac arrest revivified interest in hypothermia for stroke, resulting in Phase 1 clinical trials and plans for further development. Given the recent spate of neuroprotective therapy failures, we sought to clarify whether clinical trials of therapeutic hypothermia should be mounted in stroke patients. We reviewed the preclinical and early clinical trials of hypothermia for a variety of indications, the putative mechanisms for neuroprotection with hypothermia, and offer several hypotheses that remain to be tested in clinical trials. Therapeutic hypothermia is promising, but further Phase 1 and Phase 2 development efforts are needed to ensure that cooling of stroke patients is safe, before definitive efficacy trials.
Lyden
Patrick D
PD
Neurology and Research Services of the San Diego Veteran's Administration Medical Center, Department of Neurosciences, University of California, San Diego, CA, USA. plyden@ucsd.edu
Krieger
Derk
D
Yenari
Midori
M
Dietrich
W Dalton
WD
D001833:Body Temperature Regulation; D002986:Clinical Trials as Topic; D006801:Humans; D007036:Hypothermia, Induced / Q000379:methods; D020521:Stroke / Q000503:physiopathology / Q000628:therapy*; D013997:Time Factors