Hypothermia in acute ischemic stroke therapy.

Therapeutic hypothermia (TH) is a potent neuroprotective therapy in experimental cerebral ischemia, with multiple effects at several stages of the ischemic cascade. In animals, TH is so powerful that all preclinical stroke studies require strict temperature control. In humans, multiple clinical studies documented powerful protection with TH after accidental neonatal hypoxic-ischemic injury and global cerebral ischemia with return of spontaneous circulation after cardiac arrest. National and international guidelines recommend TH for selected survivors of global ischemia, with profound benefits seen. Recently, a study comparing target temperature 33-36°C failed to demonstrate significant effects in cardiac arrest patients. Additionally, clinical trials of TH for head trauma and stroke have so far failed to confirm benefit in humans despite a vast preclinical literature. Therefore, it is now critical to understand the fundamental explanation for the success of TH in some, but famously not all, clinical trials. TH in animals appears to work when used soon after ischemia onset; for a short duration; and at a deep target temperature.