In neonatal and adult animals, modest reduction in brain temperature (2-3°C) during ischemia and hypoxia-ischemia provides partial or complete neuroprotection. One potential mechanism for this effect is a decrease in brain energy (1) and rat pups (2, of ischemia-induced brain injury. For example, modest hypo-3 ) have demonstrated that relatively small reductions in tem-thermia attenuates the extent of brain acidosis during and perature (2-3°C) during brain ischemia or hypoxia-ischemia immediately after brain ischemia in neonatal piglets (4). Modprovides partial neuroprotection. There are multiple mecha-est hypothermia blunts the increase in concentration of excitanisms by which modest hypothermia may modulate the extent tory amino acids in brain extracellular fluid during ischemia in adult rats (5). Another potential benefit of intraischemic hypothermia is preservation of brain ATP. The latter has been Received October 10, 1994; accepted A U~U S~ 3, 1995. confirmed in adult and neonatal animals when temperature is perature also preserve brain ATP. In adult cats and rats,

ABSTRACf. Hypothermia is a frequent occurrence in newborns, and thermoregulatory management is a fundamental part of medical stabilization. Although modest reduction in brain temperature (2-3°C) before ischemia pro--vides neuroprotection in adults, the effect of modest hypothermia on immature brain has not been examined. Nineday-old swine were exposed to 15 min of incomplete global brain ischemia, with intraischemic rectal temperatures of either 38.3 % 0.4°C (n = 10, normothermic) or 35.4 % O's"C (n = 10, hypothermic). The relationship between rectal and brain temperature was delineated in preliminary experiments on four swine. Animals with intraischemic rectal temperatures maintained at either 39.5°C or 35's"C were associated with a similar magnitude of difference in brain temperature. Therefore, rectal temperature was used to monitor brain temperature for 20 animals studied subsequently. Ischemia was induced by combining neck compression with hemorrhagic hypotension and resulted in similar group values for mean arterial pressure and changes in pH and blood gases at the completion of ischemia. A clinical overall performance score and brain tissue structure were evaluated after 72 h (or earlier if animals died prematurely). Hypothermic animals had less severe stages of impairment compared with the normothermic group (p = 0.023). Hypothermic piglets had less histologic damage in the neocortex at 0.5 em beneath the brain surface (p = 0.048), the caudate nucleus (p = 0.038), and the pons{ midbrain (p = 0.04) and the same direction of effect in neocortex at 1 em beneath the surface (p = 0.07) and the cerebellum (p = 0.07) as compared with normothermic animals. The results demonstrate that a 2-3°C reduction in brain temperature during 15 min of incomplete ischemia provides partial neuroprotection in neonatal swine. iPediatr Res 35:436-442,1994) Abbreviations OPS, overall performance score MAP, mean arterial pressure CBF, cerebral blood flow ture. Busto et al. (3) and others (4, 5) have demonstrated that a 2-3"C reduction in intraischemic brain temperature of adult animals markedly attenuated neuropathologic changes. 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.A paucity of information on neonates .exists regarding the neuroprotective effects of modest hypothermia. The effects of hypothermia on brain tissue structure was examined in 7-d-old Sprague-Dawley rats subjected to hypoxia-ischemia for 3.5 h (7). At an ambient temperature of 37"C, hypoxia-ischemia resulted in extensive brain infarction , but no histologic injury occurred at 21·C, and at 29·C damage was limited to focal areas of necrosis. These observations have recently been extended to 10-d-old Sprague...

Intraischemic reduction in temperature of 2-3 degrees C (modest hypothermia) has been demonstrated to provide partial neuroprotection in neonatal animals. This investigation determined if modest hypothermia initiated immediately after brain ischemia provides neuroprotection. Piglets were studied with rectal temperature maintained during the 1st h after 15 min of brain ischemia at either 38.3 +/- 0.3 degrees C (normothermia, n = 11) or at 35.8 +/- 0.5 degrees C (modest hypothermia, n = 11). The severity of brain ischemia was similar between groups as indicated by equivalent reduction in mean blood pressure (90 +/- 15 to 24 +/- 3 versus 92 +/- 13 to 26 +/- 3 mm Hg), and changes in cerebral metabolites and intracellular pH (pH(i)) measured by magnetic resonance spectroscopy (beta-nucleoside triphosphate = 44 +/- 9 versus 42 +/- 18% of control, control = 100%, pH(i): 6.25+/- .15 versus 6.24 +/- 0.22 for normothermic and modestly hypothermic groups, respectively). In the first 90 min after ischemia, there were no differences between groups in the duration and extent of brain acidosis, and relative concentrations of phosphorylated metabolites. Categorical assessment of neurobehavior was evaluated at 72 h postischemia (n = 16), or earlier if an animal's condition deteriorated (n = 6). Postischemic hypothermia was associated with less severe stages of encephalopathy compared with normothermia (p = 0.05). Histologic neuronal injury was assessed categorically in 16 brain regions, and postischemic hypothermia resulted in less neuronal injury in temporal (p = 0.024) and occipital (p = 0.044) cortex at 10 mm beneath the cortical surface, and in the basal ganglia (p = 0.038) compared with that in normothermia. Modest hypothermia for 1 h immediately after brain ischemia provides partial neuroprotection and may represent an adjunct to resuscitative strategies.

Intraischemic modest hypothermia attenuates the severity of brain acidosis during and 30 minutes after ischemia compared with normothermic animals and supports the concept that attenuated brain acidosis is a potential mechanism by which hypothermia may reduce ischemic brain damage.