Whole Body Vibration Attenuates Brain Damage and Neuroinflammation Following Experimental Traumatic Brain Injury

Abstract

Traumatic brain injury (TBI) is still a major public health problem worldwide, and the research of neuroprotective drugs has encountered great difficulties. Whole body vibration (WBV) is a safe and powerful rehabilitative intervention in various clinical settings, but its effect on neurological diseases is not well documented. In this study, we investigated the effects of WBV pretreatment on brain damage following experimental TBI mimicked by controlled cortical impact (CCI) in mice. C57BL/6 J male mice were expose to WBV at 30 Hz twice per day for 20 days and injured by CCI. WBV had no effect on animal body weight, but significantly reduced the TBI-induced brain edema in the cortex. The results of immunostaining showed that the activation of microglia and astrocytes induced by TBI in brain sections was attenuated by WBV. In consistent, WBV markedly inhibited the expression of pro-inflammatory cytokines, while increased the levels of anti-inflammatory cytokine interleukin 10 (IL-10). In addition, WBV pretreatment alleviated neuronal apoptosis in the cortex and suppressed the cleavage of the apoptotic executive molecule caspase-1. The neurological dysfunction following TBI was determined by open field test and Morris Water Maze (MWM) assay. The results showed that motor activity, learning and memory ability were preserved by WBV compared to TBI-injured mice. In summary, our present data identified WBV as a clinically potent strategy with which to attenuate TBI-related brain damage through regulating neuroinflammation.

Keywords: GFAP; Iba-1; neuroinflammation; traumatic brain injury; whole body vibration.

FIGURE 1

Equipment and experimental design. (A) Vibration parameters shown in the vibration controller. (B) Experimental design showing the treatments and time points of various measurements.

FIGURE 2

WBV alleviates brain damage after TBI. (A) Longitudinal assessment of animals’ body weight. (B) Brain edema measurement in cerebrum, cerebellum or brainstem. Data are shown as mean ± SD. ^# p < 0.05 vs. Sham group. *p < 0.05 vs. TBI group.

FIGURE 3

WBV suppresses Iba-1 expression after TBI. (A,B) Representative images of Iba-1 immunostaining in cortex (A) and quantitative analysis (B). (C,D) Representative images of Iba-1 immunostaining in corpus callosum (C) and quantitative analysis (D). (E,F) Representative images of Iba-1 immunostaining in hippocampus (E) and quantitative analysis (F). Scale bar = 50 μm. Data are shown as mean ± SD. ^# p < 0.05 vs. Sham group. *p < 0.05 vs. TBI group.

FIGURE 4

WBV inhibits GFAP expression after TBI. (A,B) Representative images of GFAP immunostaining in cortex (A) and quantitative analysis (B). (C,D) Representative images of GFAP immunostaining in corpus callosum (C) and quantitative analysis (D). (E,F) Representative images of GFAP immunostaining in hippocampus (E) and quantitative analysis (F). Scale bar = 50 μm. Data are shown as mean ± SD. ^# p < 0.05 vs. Sham group. *p < 0.05 vs. TBI group.

FIGURE 5

WBV regulates inflammatory cytokines after TBI. (A–D) ELISA results of levels of inflammatory cytokines at 24 and 72 h after TBI: IL-1β (A), IL-6 (B), TNF-α (C) and IL-10 (D). Data are shown as mean ± SD. ^# p < 0.05 vs. Sham group. *p < 0.05 vs. TBI group.

FIGURE 6

WBV ameliorates neuronal cell death after TBI. (A–C) Representative images of TUNEL staining in injured cortex (A) and quantitative analysis of TUNEL positive cells (B) and NeuN positive cells (C). (D,E) Representative images of western blot analysis showing the expression of cleaved caspase-1 (p20) (D) and quantitative analysis (E). Scale bar = 100 μm. Data are shown as mean ± SD. ^# p < 0.05 vs. Sham group. *p < 0.05 vs. TBI group.

FIGURE 7

WBV improves exploratory behavior and general activity after TBI. (A) Longitudinal assessment of motor activity recovery. (B) Side by side longitudinal assessment of rest time. Data are shown as mean ± SD. ^# p < 0.05 vs. Sham group. *p < 0.05 vs. TBI group.

FIGURE 8

WBV attenuates learning and memory deficits after TBI. (A) Learning curves showing the latency to the platform on each day of 4 days of the learning trail. (B) Quantitative analysis of time in platform quadrant during the 60 s probe trial. Data are shown as mean ± SD. ^# p < 0.05 vs. Sham group. *p < 0.05 vs. TBI group.