Resveratrol decreases inflammation in the brain of mice with mild traumatic brain injury

Joshua W. Gatson, Ming Mei Liu, Kareem Abdelfattah, Jane G. Wigginton, Scott Smith, Steven Wolf, Joseph P. Minei

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

BACKGROUND: Following a mild traumatic brain injury (TBI) event, the secondary brain injury that persists after the initial blow to the head consists of excitotoxicity, decreased cerebral glucose levels, oxidant injury, mitochondrial dysfunction, inflammation, and neuronal cell death. To date, there are no effective interventions used at decreasing secondary brain injury after mild TBI. METHODS: In this study, male mice were treated with either placebo or resveratrol (100 mg/kg) at 5 minutes and 12 hours after mild TBI. The mice were injured using the controlled cortical impact device. In this closed-head model, a midline incision was made to access the skull and the impactor tip was aligned on the sagittal suture midway between the bregma and lambda sutures. The mice were injured at a depth of 2.0 mm, velocity of 4 m/s, and a delay time of 100 milliseconds. At 72 hours following injury, the animals were intracardially perfused with 0.9% saline followed by 10% phosphate-buffered formalin. The whole brain was removed, sliced, and stained for microglial activation (Iba1). In addition, using the enzyme-linked immunosorbent assay, tissue levels of interleukin 6 (IL-6) and IL-12 were measured in the cerebral cortex and hippocampus. RESULTS: In this study, we found that in the placebo treatment group, there was a significant increase in Iba1 staining in the brain. The levels of microglial activation was reduced by resveratrol in the cerebral cortex (p < 0.001), corpus callosum (p < 0.001), and dentate gyrus (p < 0.005) brain regions after mild TBI. In addition to Iba1, resveratrol decreased the brain levels of IL-6 (p < 0.0001) and IL-12 (p < 0.004), which were observed in the hippocampus of the placebo group. In our model, no increase of IL-6 or IL-12 was observed in the cerebral cortex following TBI. CONCLUSION: Resveratrol given acutely after TBI results in a decrease in neuroinflammation. These results suggest that resveratrol may be beneficial in reducing secondary brain injury after experiencing a mild TBI.

Original languageEnglish (US)
Pages (from-to)470-475
Number of pages6
JournalJournal of Trauma and Acute Care Surgery
Volume74
Issue number2
DOIs
StatePublished - Feb 1 2013
Externally publishedYes

Keywords

  • IL-12
  • IL-6
  • Mice
  • Microglia
  • Resveratrol
  • TBI

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Surgery

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