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) |
|---|---|
| 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 |
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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 journal › Article
}
TY - JOUR
T1 - Modulation of nuclear factor-κB activation and decreased markers of neurological injury associated with hypothermic therapy in experimental bacterial meningitis
AU - Irazuzta, Jose E.
AU - Pretzlaff, Robert K.
AU - Zingarelli, Basilia
AU - Xue, Vivian
AU - Zemlan, Frank
PY - 2002/11/1
Y1 - 2002/11/1
N2 - 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.
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.
KW - Brain injury
KW - Cleaved tau protein
KW - Critical care
KW - Hypothermia
KW - Long-term outcome
KW - Meningitis
KW - Neurobehavioral performance
KW - Nuclear factor-κB
UR - http://www.scopus.com/inward/record.url?scp=0036851142&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036851142&partnerID=8YFLogxK
M3 - Article
C2 - 12441769
AN - SCOPUS:0036851142
VL - 30
SP - 2553
EP - 2559
JO - Critical Care Medicine
JF - Critical Care Medicine
SN - 0090-3493
IS - 11
ER -