Modulation of nuclear factor-κB activation and decreased markers of neurological injury associated with hypothermic therapy in experimental bacterial meningitis

Jose E. Irazuzta, Robert K. Pretzlaff, Basilia Zingarelli, Vivian Xue, Frank Zemlan

Research output: Contribution to journalArticle

40 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)2553-2559
Number of pages7
JournalCritical Care Medicine
Volume30
Issue number11
StatePublished - Nov 1 2002
Externally publishedYes

Fingerprint

Investigational Therapies
Bacterial Meningitides
Hypothermia
Wounds and Injuries
Brain Injuries
Biomarkers
Meningitis
Heat-Shock Response
Rewarming
Heat-Shock Proteins
Serum
Wistar Rats
Suspensions
Placebos
Prospective Studies
Anti-Bacterial Agents
Temperature
Water
Brain
Research

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

Cite this

Modulation of nuclear factor-κB activation and decreased markers of neurological injury associated with hypothermic therapy in experimental bacterial meningitis. / Irazuzta, Jose E.; Pretzlaff, Robert K.; Zingarelli, Basilia; Xue, Vivian; Zemlan, Frank.

In: Critical Care Medicine, Vol. 30, No. 11, 01.11.2002, p. 2553-2559.

Research output: Contribution to journalArticle

Irazuzta, Jose E. ; Pretzlaff, Robert K. ; Zingarelli, Basilia ; Xue, Vivian ; Zemlan, Frank. / Modulation of nuclear factor-κB activation and decreased markers of neurological injury associated with hypothermic therapy in experimental bacterial meningitis. In: Critical Care Medicine. 2002 ; Vol. 30, No. 11. pp. 2553-2559.
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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.",
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AU - Xue, Vivian

AU - Zemlan, Frank

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AB - 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.

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