Marked Protection by Moderate Hypothermia after Experimental Traumatic Brain Injury

Abstract

Summary: These experiments examined the effects of moderate hypothermia on mortality and neurological def icits observed after experimental traumatic brain injury (TBI) in the rat. Brain temperature was measured contin uously in all experiments by intraparenchymal probes, Brain cooling was induced by partial immersion (skin pro tected by a plastic barrier) in a water bath (OOe) under general anesthesia (1.5% halothane170% nitrous oxide/ 30% oxygen). In experiment I, we examined the effects of moderate hypothermia induced prior to injury on mortal ity following fluid percussion TBI. Rats were cooled to 36°e (n = 16), 33°e (n = 17), or 300e (n = II) prior to injury and maintained at their target temperature for I h after injury. There was a significant (p < 0.04) reduction in mortality by a brain temperature of 30oe. The mortality rate at 36°e was 37.5%, at 33°e was 41 %, and at 300e wasThe cerebral protective effects of profound hypo thermia «18°C) have been known for many years. As early as 1950, reports of cerebral protection from global ischemia by profound hypothermia in animals stimulated clinical interest (Mohri and Me rendino, 1969). By 1955, 100 cardiac surgical cases had been performed under deep hypothermia with cardiac arrest (Mohri and Merendino, 1969). As pump oxygenators became more efficient, deep hy pothermia and cardiac arrest were only occasion ally used in adult cardiac surgery (Crawford and Saleh, 1981). In pediatric cardiac surgery, however, conditions were encountered routinely where total cessation of circulation at temperatures of 17-20°C Abbreviations used: ANOYA, analysis of variance; TB1, trau matic brain injury, 114 9.1 %. In experiment II, we examined the effects of mod erate hypothermia or hyperthermia initiated after TBI 01 long-term behavioral deficits. Rats were cooled to 36°e (I = 10), 33°e (n = 10), or 300e (n = 10) or warmed to 38°( (n = 10) or 400e (n = 12) starting at 5 min after injury an( maintained at their target temperatures for I h. Hypother mia-treated rats had significantly less beam-walking beam-balance, and body weight loss deficits compared t( normothermic (38°C) rats. The greatest protection wa: observed in the 300e hypothermia group, Since a temper ature of 300e can be induced in humans by surface cool ing without coagulopathy or ventricular fibrillation, hy pothermia to 300e may have potential clinical value fOJ treatment of human brain injury.

Development of Posttraumatic Hyperthermia after Traumatic Brain Injury in Rats is Associated with Increased Periventricular Inflammation

“…Although these factors have been shown to relate to poorer outcome after TBI (Jeremitsky et al, 2003), isolated hypothermia may or may not be causative of poor outcome. Because it has also been suggested that therapeutic postinjury hypothermia is neuroprotective (Clifton et al, 1991;Dietrich 1992;Marion et al, 1997;Kinoshita et al, 2002a, b), the findings of this study provide additional information to aid in the design of future preclinical neuroprotection studies. Temperature should be extensively monitored and controlled after randomization in the postinjury period to prevent the additional hypothermia as a confounding variable in the evaluation of experimental treatments.…”

Neurotoxic Zinc Translocation into Hippocampal Neurons is Inhibited by Hypothermia and is Aggravated by Hyperthermia after Traumatic Brain Injury in Rats

“…In that paper, we used a weight Hypothermia, initiated either before or immediately after TBI, substantially ameliorates the biochemical, histopathologic and behavioral sequelae of experimental TBI. Clifton et al (1991) reported marked reduction of mortality after fluid percussion injury (FPI) in rats by preinjury induction of moderate hypothermia (301C) and improved behavioral outcome if temperature was reduced to 331C or 301C 5 mins after FPI. After controlled cortical impact in rats, mild posttraumatic hypothermia (321C) reduced mortality (Clark et al, 1996).…”

“…Systemic hypothermia, which inhibits neuronal release of glutamate, prevents or reduces neuronal death after cerebral ischemia (Busto et al, 1987(Busto et al, , 1989Churn et al, 1990;Dietrich et al, 1993;Hu et al, 1995;Kil et al, 1996;Minamisawa et al, 1990a;Rosomoff, 1959;Tanimoto and Okada, 1987), prolonged seizures (Liu et al, 1993;Lundgren et al, 1994) and traumatic brain injury (TBI) (Clifton et al, 1991), especially if initiated before an insult. Conversely, hyperthermia aggravates the neuronal death produced by those conditions (Dietrich, 1992;Dietrich et al, 1996;Lundgren et al, 1994;Minamisawa et al, 1990b).…”

Effects of Moderate Hypothermia on Constitutive and Inducible Nitric Oxide Synthase Activities After Traumatic Brain Injury in the Rat

“…The next day, an F-P device was used to produce experimental TBI (Dixon et al, 1987;Clifton et al, 1991). The rats were reanesthetized with 3.0% halothane induction in a gas mixture of 70% nitrous oxide and 30% oxygen and maintained at 0.5% halothane.…”