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.

BackgroundA traumatic brain injury (TBI) event is a devastating injury to the brain that may result in heightened inflammation, neurodegeneration, and subsequent cognitive and mood deficits. TBI victims with co-morbidities such as heart disease, diabetes, or obesity may be more vulnerable to the secondary brain injury that follows the initial insult. Compared to lean individuals, obese subjects tend to have worse clinical outcomes and higher mortality rates after trauma.MethodsTo elucidate whether obesity predisposes individuals to worse outcomes after TBI, we subjected adult lean and obese male/female mice to a mild TBI. The injury was administered using a controlled skull impact (CSI) device. Lean or obese 6-month-old C57 BL/6 mice were subjected once to a mild TBI. Additionally, at day 30 after injury, both the lean and obese mice were tested for increased anxiety using the open field test.ResultsAt day 30 after TBI, compared to the lean mice, we found heightened microglial (MG) activation in the cerebral cortex, corpus callosum, and hypothalamus. Another compelling finding was that, compared to the non-injured obese male control mice, the obese TBI mice had a decrease in the rate of weight gain and serum corticosterone levels at day 30 after injury. Additionally, the injured obese mice displayed higher levels of anxiety as determined by a significant decrease in time spent in the non-peripheral zones in the open field test. In contrast to the obese males, the obese female mice did not exhibit increases in the number of active MG in the brain, changes in weight gain/corticosterone levels, or increased anxiety at day 30 after TBI.ConclusionsThe data presented here suggests that obese mice have worse outcomes compared to lean mice after mild TBI. Also, the obese males have worse outcomes than the injured female mice. This data may explain the sequela of chronic secondary brain injury in obese adults after a single mild TBI. Also, this report may help shape how the overweight/obese populations are monitored over the days and months following a TBI.

In various animal and human studies, early administration of 17b-estradiol, a strong antioxidant, anti-inflammatory, and anti-apoptotic agent, significantly decreases the severity of injury in the brain associated with cell death. Estrone, the predominant estrogen in postmenopausal women, has been shown to be a promising neuroprotective agent. The overall goal of this project was to determine if estrone mitigates secondary injury following traumatic brain injury (TBI) in rats. Male rats were given either placebo (corn oil) or estrone (0.5 mg/ kg) at 30 min after severe TBI. Using a controlled cortical impact device in rats that underwent a craniotomy, the right parietal cortex was injured using the impactor tip. Non-injured control and sham animals were also included. At 72 h following injury, the animals were perfused intracardially with 0.9% saline followed by 10% phosphate-buffered formalin. The whole brain was removed, sliced, and stained for TUNEL-positive cells. Estrone decreased cortical lesion volume (p < 0.01) and neuronal injury (p < 0.001), and it reduced cerebral cortical levels of TUNEL-positive staining (p < 0.0001), and decreased numbers of TUNEL-positive cells in the corpus callosum (p < 0.03). We assessed the levels of b-amyloid in the injured animals and found that estrone significantly decreased the cortical levels of b-amyloid after brain injury. Cortical levels of phospho-ERK1/2 were significantly (p < 0.01) increased by estrone. This increase was associated with an increase in phospho-CREB levels (p < 0.021), and brain-derived neurotrophic factor (BDNF) expression (p < 0.0006). In conclusion, estrone given acutely after injury increases the signaling of protective pathways such as the ERK1/2 and BDNF pathways, decreases ischemic secondary injury, and decreases apoptotic-mediated cell death. These results suggest that estrone may afford protection to those suffering from TBI.

Background Muscle loss is a sequela of severe burn and critical illness with bed rest contributing significantly to atrophy. We hypothesize that exercise will mitigate muscle loss after burn with bed rest. Materials and Methods Male rats were assigned to sham ambulatory (S/A), burn ambulatory (B/A), sham hindlimb unloading (S/H), or burn hindlimb unloading (B/H). Rats received a 40% scald burn or sham and were ambulatory or placed in hindlimb unloading, a model of bed rest. Half performed twice-daily resistance climbing. Hindlimb isometric forces were measured on day 14. Results Soleus mass and muscle function were not affected by burn alone. Mass was significantly lower in hindlimb unloading (79 vs.139 mg, p<0.001) and no exercise (103 vs.115 mg, p<0.01). Exercise significantly increased soleus mass in B/H (86 vs. 77mg, p<0.01). Hindlimb unloading significantly decreased muscle force in the twitch (31 vs. 12g, p<0.001), tetanic (55 vs. 148 g, p<0.001), and specific tetanic measurements (12 vs. 22 N/cm2, p<0.001). Effects of exercise on force depended on other factors. In B/H, exercise significantly increased twitch (14 vs. 8 g, p<0.05) and specific tetanic force (14 vs. 7 N/cm2, p<0.01). Fatigue index was lower in ambulatory (55%) and exercise (52%) versus hindlimb (69%, p=0.03) and no exercise (73%, p=0.002). Conclusions Hindlimb unloading is a significant factor in muscle atrophy. Exercise increased the soleus muscle mass, twitch, and specific force in this model. However, the fatigue index decreased with exercise in all groups. This suggests exercise contributes to functional muscle change in this model of disuse and critical illness.