Posttraumatic hypothermia

M.Y. Globus, O. Alonso, W.A. Dietrich, R. Busto, and M.D. Ginsberg, Glutamate release and free radical production following brain injury effects of posttraumatic hypothermia. J. Neurochem. 65, 1704-1711 (1995). 

Quantitative strategies to evaluate the effects of posttraumatic temperature patterns of neuronal vulnerability in models of TBI have been conducted in several laboratories. The effect of posttraumatic hypothermia on histopathological outcome was first evaluated in a model of moderate parasagittal fluid percussion (F-P) brain injury (3). In that... 

Trauma-induced axonal injury (TAI)is an important feature of human TBI. Some investigations have reported that moderate hypothermia can also reduce the generation of traumatically induced axonal injury (6,13). In one study, moderate hypothermia (32°C/4 h) initiated 10 min or 25 min after injury significantly reduced the number of abnormally stained axonal profiles (6). A study by Koizumi and Povlishock (13) reported that posttraumatic hypothermia (32°C/1 h) initiated as late as 1 h after trauma significantly reduced the density of amyloid precursor protein (APP) immunoreacti ve damaged axons within the corticospinal tract. Together, these data indicate that posttraumatic hypothermia in two models of TBI provides substantial protection in terms of axonal... 

In clinical studies, posttraumatic hypothermia has also been reported to be beneficial (7,18). Marion et al. (18) demonstrated that posttraumatic hypothermia (32-33°C/24 h) in patients with severe TBI and Glasgow Coma Scores of 5-7 on admission hastened neurologic recovery and may have improved outcome. These clinical findings are impor-... 

Matsushita Y., BramlettH. M., Alonso O., and Dietrich W. D. (2001) Posttraumatic hypothermia is neuroprotective in amodel of traumatic brain injury complicated by a secondary hypoxic insult. Crit. Care Med. 29, 2060-2066. 

Suehiro E., Singleton R. H., Stone J. R., and Povlishock J. T. (2001) The immunophilin ligand FK506 attenuates the axonal damage associated with rapid rewarming following posttraumatic hypothermia. Exp. Neurol. 172,199-210. 

Chatzipanteli K., Alonso O. F., Kraydieh S., and Dietrich W. D. (2000) Importance of posttraumatic hypothermia and hyperthermia on the inflammatory response after fluid percussion brain injury biochemical and immunocytochemical studies. J. Cereb. Blood Flow Metab. 20,531-542. 

Smith S. L. and Hall E. D. (1996) Mild pre- and posttraumatic hypothermia attenuates blood-brain barrier damage following controlled cortical impact injury in the rat. J. Neurotrauma 13,1-9. 

Posttraumatic hyperthermia (>39°C), in contrast to hypothermia, has been shown in experimental models of TBI to worsen outcome. In one study, artificially elevating brain temperature to 39°C for a 3-h period, 24 h after moderate parasagittal F-P injury increased mortality, compared with normothermic rats (1). Delayed hyperthermia also significantly increased contusion volume and increased the frequency of abnormal-appearing myelinated axons. 

Extravasation of polymorphonuclear leukocytes (PMNs) in the area of injury occurs very early after injury in several different models of experimental TBI, and has been shown to correlate with the development of cerebral edema (101,102). Early canine studies conducted by Rosomoff (16,57) demonstrated that treatment with hypothermia decreased the posttraumatic cellular inflammatory response incited by experimental head injury compared to normothermic controls. This effect of hypothermia is likely mediated by several mechanisms including preservation of the BBB, thereby limiting extravasation of inflammatory cells and mediators into the area of injury (103), suppressing release of cytokines (22), and reducing CBF. 

Hypothermia-induced coagulopathy in patients with severe TBI has important clinical implications. In addition to the intracranial hemorrhages caused by their primary traumatic injury, these patients have a 20-30% incidence of delayed posttraumatic intracranial hemorrhage. However, at least one report found that treatment with moderate hypothermia did not result in increased rates of secondary delayed intracranial hemorrhages as compared to normothermic controls (19). 

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