• Jose E Irazuzta, Robert K Pretzlaff, Basilia Zingarelli, Vivian Xue, and Frank Zemlan.
• Division of Critical Care Medicine, Tufts University, The Floating Hospital for Children, New England Medical Center, Boston, MA, USA.
• Crit. Care Med. 2002 Nov 1;30(11):2553-9.

ObjectiveThis study was designed to evaluate the use of moderate hypothermia in a model of meningitis-induced brain injury and its effect on the activation of nuclear factor-kappaB, biological markers of neuronal injury, and neurobehavioral performance.DesignRandomized, prospective animal study.SettingUniversity research laboratory.SubjectsMale Wistar rats.InterventionsAnimals underwent a basilar cistern tap receiving either sterile saline as a placebo or an equivalent volume of a group B streptococcal suspension. Sixteen hours after inoculation, animals were stratified by their clinical severity score, were randomized to either hypothermic (32-34 degrees C) or normothermic (37-39 degrees C) conditions, and received antibiotics. Hypothermic animals were kept under these temperature conditions for 6 hrs before rewarming. Two protocols were used. For the first protocol, changes in nuclear factor-kappaB activation and heat shock protein induction at 24 hrs and 48 hrs after inoculation were evaluated. In the second protocol, serum C-tau concentrations at 5 days and neurobehavioral performances at 3 wks were assessed.Measurements And Main ResultsMeningitis triggered a >50% increase in cerebral nuclear factor-kappaB activation. The addition of a 6-hr period of hypothermia reduced nuclear factor-kappaB activation by 32% when measured at the end of the hypothermic period. At 48 hrs, this decrease in nuclear factor-kappaB activation was no longer apparent, but there was a significant decrease in the heat shock response. Serum C-tau concentrations at 5 days postinjury, a biomarker of brain injury, were reduced by 69% in hypothermic treated animals. Furthermore, hypothermia reduced the brain water content of infected animals. However, hypothermia did not improve the animals' neurobehavioral performance.ConclusionThe findings from this study suggest that hypothermia produces a transitory attenuation of nuclear factor-kappaB activation in meningitic brain injury and improvement in some biomarkers of neuronal injury. The consequence of intermittent suppression of nuclear factor-kappaB activation by inducing specific periods of hypothermia requires further study.

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