Neither any
neuroprotective drug has been shown to be beneficial in improving the outcome of severe
traumatic brain injury (TBI) nor has any prophylactically-
induced moderate hypothermia shown any beneficial effect on outcome in severe TBI, despite the optimism generated by preclinical studies. This contrasts with the paradox that
hypothermia still is the most powerful neuroprotective method in experimental models because of its ability to influence the multiple biochemical cascades that are set in motion after TBI. The aim of this short review is to highlight the most recent developments concerning the pathophysiology of severe TBI, to review new data on thermoregulation and
induced hypothermia, the regulation of core and brain temperature in mammals and the multiplicity of effects of
hypothermia in the pathophysiology of TBI. Many experimental studies in the last decade have again confirmed that moderate
hypothermia confers protection against ischemic and non-ischemic
brain hypoxia,
traumatic brain injury, anoxic injury following
resuscitation after
cardiac arrest and other neurological insults. Many posttraumatic adverse events that occur in the injured brain at a cellular and molecular level are highly temperature-sensitive and are thus a good target for
induced hypothermia. The basic mechanisms through which
hypothermia protects the brain are clearly multifactorial and include at least the following: reduction in brain metabolic rate, effects on cerebral blood flow, reduction of the critical threshold for
oxygen delivery, blockade of excitotoxic mechanisms,
calcium antagonism, preservation of
protein synthesis, reduction of brain thermopooling, a decrease in
edema formation, modulation of the inflammatory response, neuroprotection of the white matter and modulation of apoptotic cell death. The new developments discussed in this review indicate that, by targeting many of the abnormal neurochemical cascades initiated after TBI,
induced hypothermia may modulate neurotoxicity and, consequently, may play a unique role in opening up new therapeutic avenues for treating severe TBI and improving its devastating effects. Furthermore, greater understanding of the pathophysiology of TBI, new data from both basic and clinical research, the good clinical results obtained in randomized clinical trials in
cardiac arrest and better and more reliable cooling methods have given
hypothermia a second chance in treating TBI patients. A critical evaluation of
hypothermia is therefore mandatory to elucidate the reasons for previous failures and to design further multicenter randomized clinical trials that would definitively confirm or refute the potential of this therapeutic modality in the management of severe
traumatic brain injuries.