Neuroprotectants: Temperature

Introduction

The history of therapeutic hypothermia (HYPO) as a treatment for brain injury is quite a fascinating one. For millennia, cooling has been used to reduce edema and inflammation. Hippocrates recommended using ice packs on wounded soldiers. However, it was Napoleon’s surgeon Dominique-Jean Larrey (1766–1842) who noted the benefit of HYPO after he observed that wounded soldiers who stayed closer to the fire were likely to die earlier . Experimental studies on HYPO began in the late 1800s and early 1900s when it was noted by Stefani, Deganello, and Trendelenburg that cooling reduces brain activity and metabolism . In the 1940s and 1950s, small clinical trials and animal experiments indicated that HYPO improved outcome, although later unsuccessful studies tempered enthusiasm for this treatment for decades. In the late 1980s and early 1990s, meticulous animal research confirmed that HYPO is a powerful neuroprotectant against ischemia . Indeed, of over one thousand treatments developed in animal models, HYPO is the only one that has been repeatedly successful in clinical trials, although there is still controversy.

A key challenge in HYPO research was, and still is, to find optimal cooling parameters (depth, duration, and delay) that cause the fewest complications while providing significant benefit. To answer this, one must consider how insult severity, comorbidities, cooling method, and other factors influence treatment efficacy and choice of treatment parameters. Here we discuss animal research that has sought to define cooling protocols in an effort to successfully translate this treatment to the ischemic and hemorrhagic stroke patient population.