Abstract
Objective: This 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-κB, biological markers of neuronal injury, and neurobehavioral performance. Design: Randomized, prospective animal study. Setting: University research laboratory. Subjects: Male Wistar rats. Interventions: Animals 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°C) or normothermic (37-39°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-κB 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 Results: Meningitis triggered a >50% increase in cerebral nuclear factor-κB activation. The addition of a 6-hr period of hypothermia reduced nuclear factor-κB activation by 32% when measured at the end of the hypothermic period. At 48 hrs, this decrease in nuclear factor-κB 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. Conclusion: The findings from this study suggest that hypothermia produces a transitory attenuation of nuclear factor-κB activation in meningitic brain injury and improvement in some biomarkers of neuronal injury. The consequence of intermittent suppression of nuclear factor-κB activation by inducing specific periods of hypothermia requires further study.
Original language | English (US) |
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Pages (from-to) | 2553-2559 |
Number of pages | 7 |
Journal | Critical Care Medicine |
Volume | 30 |
Issue number | 11 |
State | Published - Nov 1 2002 |
Externally published | Yes |
Keywords
- Brain injury
- Cleaved tau protein
- Critical care
- Hypothermia
- Long-term outcome
- Meningitis
- Neurobehavioral performance
- Nuclear factor-κB
ASJC Scopus subject areas
- Critical Care and Intensive Care Medicine