The Influence of Mild Body and Brain Hypothermia on Ischemic Brain Damage

Abstract

Summary: The influence of brain and body temperature on ischemic brain damage, notably on the density and distribution of selective neuronal vulnerability, was stud ied in SPF-Wistar rats subjected to 15 min of forebrain ischemia induced by bilateral occlusion of the common carotid arteries combined with arterial hypotension (50 mm Hg) in a room air environment. In one group of ani mals, the body temperature was maintained at 37°C but no attempt was made to prevent heat losses from the ischemic brain; i. e. , the head was not heated during isch emia. Under those conditions the temperature of the cau doputamen and at a subcutaneous site over the skull bone spontaneously fell to � 32°C. In four other groups, both the rectal and the subcutaneous skull temperatures were maintained at 38, 37, 35, and 33°C during the ischemia. Our results confirm those recently reported when brain temperature was varied during 20 min of ischemia, with body temperature kept constant. Thus, the histopatholog ical outcome of the brain damage, as assessed after 7 days It has been known for a long time that moderate to deep hypothermia increases the tolerance of the brain to ischemic insults (e.g., Hirsch et aI., 1957;Rosomoff, 1959;Boyd and Connolly, 1961; Siebke et aI., 1975; Haneda et aI., 1986). This increase in tolerance has been extensively exploited in the clinic (Fay, 1959;Brunberg et al., 1974; Spetzler et aI., 1988). To take an extreme example, by reducing the brain temperature to 5-8°C, White and associ ates (1973) were able to interrupt brain circulation for 60 min in primates. In patients, hypothermia of such magnitude allows surgical intervention of a type that could not be tolerated at normal temper atures. The procedure has apparently no untoward effects on postischemic brain function. 365of recovery, was strongly temperature dependent. Whereas ischemia at 37-38°C consistently caused neuro nal necrosis in the hippocampus, neocortex, and caudo putamen, spontaneous cooling of the brain during isch emia at a rectal temperature of 37°C significantly reduced the ischemic damage. Intentional lowering of temperature to 35°C markedly reduced and to 33°C virtually prevented neuronal necrosis in some but not all of the regions stud ied. While damage to the caudoputamen was extremely temperature sensitive, that affecting the CA 1 sector of the hippocampus, and particularly the lateral reticular nu cleus of the thalamus, was less so. Our results suggest that whatever biochemical events are responsible for se lective neuronal vulnerability, they are temperature sen sitive; however, since there are differences in sensitivity between different parts of the brain, more than one mech anism may be involved. Key Words: Cerebral ischemia Hypothermia-Neuronal damage.In 1962, Hirsch and Muller published an exten sive series of experimental results that suggested that even very small differences in brain tempera ture affect the neurological and histopathological outcome of complete global ischemia. The authors, who conducted their experiments ...

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

“…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).…”

Modest Hypothermia Provides Partial Neuroprotection for Ischemic Neonatal Brain

“…These observations were independent of the manner in which the brain was cooled. Modest hypothermia during ischemia resulted in different degrees ofneuroprotection in different brain regions (3,6). Thus, small changes in brain temperature may contribute to some of the inconsistencies in the literature regarding the effects of pharmacologic agents and the impact of brain ischemia on neurologic outcome.…”

Differences between brain and rectal temperatures during routine critical care of patients with severe traumatic brain injury*

“…Using these conventional body sites, temperatures greater than 38.5°C are commonly encountered during neurocritical care [2,3] and cause concern. In animal models of cerebral ischaemia [4][5][6][7] and trauma [8,9] a rise in body core temperature in excess of 38°C is associated with increased neuronal damage. In stroke patients a rise in body temperature independently predicts poor outcome [10] and increased mortality [11][12][13][14] but when the human brain is injured by trauma, the evidence for a relationship between raised body temperature and worse neurological outcome is not as clear [15,16].…”