TY - JOUR
T1 - The effect of therapeutic hypothermia on the expression of inflammatory response genes following moderate traumatic brain injury in the rat
AU - Truettner, Jessie S.
AU - Suzuki, Takamoto
AU - Dietrich, W. Dalton
N1 - Funding Information:
This study was supported by the National Institutes of Health, grants 5P50-NS30291 and NS42133. The authors would like to thank Charlaine Rowlette for excellent editorial assistance and manuscript preparation.
PY - 2005/8/18
Y1 - 2005/8/18
N2 - Traumatic brain injury (TBI) initiates a cascade of cellular and molecular responses including both pro- and anti-inflammatory. Although post-traumatic hypothermia has been shown to improve outcome in various models of brain injury, the underlying mechanisms responsible for these effects have not been clarified. In this study, inflammation cDNA arrays and semi-quantitative RT-PCR were used to detect genes that are differentially regulated after TBI. In addition, the effect of post-traumatic hypothermia on the expression of selective genes was also studied. Rats (n = 6-8 per group) underwent moderate fluid-percussion (F-P) brain injury with and without hypothermic treatment (33°C/3 h). RNA from 3-h or 24-h survival was analyzed for the expression of IL1-β, IL2, IL6, TGF-β2, growth-regulated oncogene (GRO), migration inhibitory factor (MIF), and MCP (a transcription factor). The interleukins IL-1β, IL-2, and IL-6 and TGF-β and GRO were strongly upregulated early and transiently from 2- to 30-fold over sham at 3 h, with normalization by 24 h. In contrast, the expressions of MIF and MCP were both reduced by TBI compared to sham. Post-traumatic hypothermia had no significant effect on the acute expression of the majority of genes investigated. However, the expression of TGF-β2 at 24 h was significantly reduced by temperature manipulation. The mechanism by which post-traumatic hypothermia is protective may not involve a general genetic response of the inflammatory genes. However, specific genes, including TGF-β2, may be altered and effect cell death mechanisms after TBI. Hypothermia differentially regulates certain genes and may target more delayed responses underlying the secondary damage following TBI.
AB - Traumatic brain injury (TBI) initiates a cascade of cellular and molecular responses including both pro- and anti-inflammatory. Although post-traumatic hypothermia has been shown to improve outcome in various models of brain injury, the underlying mechanisms responsible for these effects have not been clarified. In this study, inflammation cDNA arrays and semi-quantitative RT-PCR were used to detect genes that are differentially regulated after TBI. In addition, the effect of post-traumatic hypothermia on the expression of selective genes was also studied. Rats (n = 6-8 per group) underwent moderate fluid-percussion (F-P) brain injury with and without hypothermic treatment (33°C/3 h). RNA from 3-h or 24-h survival was analyzed for the expression of IL1-β, IL2, IL6, TGF-β2, growth-regulated oncogene (GRO), migration inhibitory factor (MIF), and MCP (a transcription factor). The interleukins IL-1β, IL-2, and IL-6 and TGF-β and GRO were strongly upregulated early and transiently from 2- to 30-fold over sham at 3 h, with normalization by 24 h. In contrast, the expressions of MIF and MCP were both reduced by TBI compared to sham. Post-traumatic hypothermia had no significant effect on the acute expression of the majority of genes investigated. However, the expression of TGF-β2 at 24 h was significantly reduced by temperature manipulation. The mechanism by which post-traumatic hypothermia is protective may not involve a general genetic response of the inflammatory genes. However, specific genes, including TGF-β2, may be altered and effect cell death mechanisms after TBI. Hypothermia differentially regulates certain genes and may target more delayed responses underlying the secondary damage following TBI.
KW - Gene array
KW - Hypothermia
KW - Inflammation
KW - Protection
KW - Trauma
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U2 - 10.1016/j.molbrainres.2005.04.006
DO - 10.1016/j.molbrainres.2005.04.006
M3 - Article
C2 - 15922484
AN - SCOPUS:23744490946
VL - 138
SP - 124
EP - 134
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 2
ER -