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


CONCLUSIONS
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.
Division of Burn/Trauma/Critical Care, Department of Surgery, University of Texas, Southwestern Medical Center, Dallas, Texas 75390-9160, USA. joshua.gatson@utsouthwestern.edu
Joshua W
JW
Gatson
Ming-Mei
MM
Liu
Kareem
K
Abdelfattah
Jane G
JG
Wigginton
Scott
S
Smith
Steven
S
Wolf
Joseph P
JP
Minei
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004660:Encephalitis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects; D018664:Interleukin-12 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D000077185:Resveratrol; D013267:Stilbenes / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015850:Interleukin-6; D013267:Stilbenes; D018664:Interleukin-12; D000077185:Resveratrol