Tumor necrosis factor α expression and protein levels after fluid percussion injury in rats: The effect of injury severity and brain temperature

Elizabeth A. Vitarbo, Katina Chatzipanteli, Kosaku Kinoshita, Jessie S. Truettner, Ofelia F. Alonso, W. Dalton Dietrich

Research output: Contribution to journalArticle

93 Scopus citations

Abstract

OBJECTIVE: Tumor necrosis factor α (TNFα) is elevated in some models of traumatic brain injury (TBI). However, it is unclear how TNFα messenger ribonucleic acid (mRNA) expression and protein levels are affected by injury severity and post-traumatic temperature modification. This study determined the regional and temporal profile of TNFα levels after moderate and severe TBI and assessed the effects of post-traumatic hypothermia or hyperthermia on this proinflammatory cytokine. METHODS: Adult male Sprague-Dawley rats were subjected to sham procedures (no injury), moderate fluid-percussion TBI (1.8-2.2 atm), or severe fluid-percussion TBI (2.4-2.6 atm). After 1 to 72 hours of survival, animals were killed, and brain samples, cerebrospinal fluid, and serum were harvested for enzyme-linked immunosorbent assay quantification of TNFα levels. In a subsequent study, a 3-hour period of post-traumatic hypothermia (33°C) or hyperthermia (39.5°C) was applied, followed by immediate killing and cytokine assay. Another group was subjected to moderate TBI (1.8-2.2 atm), followed by killing at 15 minutes or at 1, 3, or 24 hours for TNFα reverse transcriptase-polymerase chain reaction analysis. RESULTS: A significant increase in TNFα mRNA and protein levels in cellular lysates of injured cortex and ipsilateral hippocampus was noted by 1 hour after TBI; it was sustained to 3 hours, followed by a rapid decline. Increased injury severity was associated with increased protein levels at remote injury sites and in the injured cerebral cortex at 72 hours. Post-traumatic hypothermia significantly reduced TNFα mRNA expression in the hippocampus compared with that in normothermic rats. In contrast, no temperature effects on TNFα protein levels were documented. CONCLUSION: Rapid and marked increase in TNFα mRNA expression and protein levels follows moderate and severe TBI. Injury severity and post-traumatic temperature play a modest but significant role on TNFα expression and protein levels. These findings suggest that the effects of post-traumatic temperature on histopathological and behavioral outcome primarily may involve secondary mediators that do not operate directly through their effect on TNFα.

Original languageEnglish (US)
Pages (from-to)416-424
Number of pages9
JournalNeurosurgery
Volume55
Issue number2
DOIs
StatePublished - Aug 2004

Keywords

  • Hyperthermia
  • Hypothermia
  • Inflammation
  • Secondary injury
  • Traumatic brain injury
  • Tumor necrosis factor α

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

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