Abstract
BackgroundRepetitive mild traumatic brain injuries (rmTBI) are associated with cognitive deficits, inflammation, and stress-related events. We tested the effect of nutrient intake on the impact of rmTBI in an animal model of chronic traumatic encephalopathy (CTE) to study the pathophysiological mechanisms underlying this model. We used a between group design rmTBI closed head injuries in mice, compared to a control and nutrient-treated groups.MethodsOur model allows for controlled, repetitive closed head impacts to mice. Briefly, 24-week-old mice were divided into five groups: control, rmTBI, and rmTBI with nutrients (2% of NF-216, NF-316 and NF-416). rmTBI mice received four concussive impacts over 7 days. Mice were treated with NutriFusion diets for 2 months prior to the rmTBI and until euthanasia (6 months). Mice were then subsequently euthanized for macro- and micro-histopathologic analysis for various times up to 6 months after the last TBI received. Animals were examined behaviorally, and brain sections were immunostained for glial fibrillary acidic protein (GFAP) for astrocytes, iba-1 for activated microglia, and AT8 for phosphorylated tau protein.ResultsAnimals on nutrient diets showed attenuated behavioral changes. The brains from all mice lacked macroscopic tissue damage at all time points. The rmTBI resulted in a marked neuroinflammatory response, with persistent and widespread astrogliosis and microglial activation, as well as significantly elevated phospho-tau immunoreactivity to 6 months. Mice treated with diets had significantly reduced inflammation and phospho-tau staining.ConclusionsThe neuropathological findings in the rmTBI mice showed histopathological hallmarks of CTE, including increased astrogliosis, microglial activation, and hyperphosphorylated tau protein accumulation, while mice treated with diets had attenuated disease process. These studies demonstrate that consumption of nutrient-rich diets reduced disease progression.
Highlights
Repetitive mild traumatic brain injuries are associated with cognitive deficits, inflammation, and stress-related events
The results demonstrated that diets high in phytonutrients were able to attenuate the “chronic traumatic encephalopathy (CTE)-like” pathology provoked by the Repetitive mild traumatic brain injuries (rmTBI)
The results suggest that supplementation of mice with the enhanced diets limited the extent of the CTE, reduced inflammation, and altered pathways typical of CTE
Summary
Repetitive mild traumatic brain injuries (rmTBI) are associated with cognitive deficits, inflammation, and stress-related events. Mild traumatic brain injury (mTBI) is a result of concussive head traumas that are considered a growing issue, with millions of sports-, military-, and recreation-related concussions occurring each year [1, 2]. CTE has a myriad of clinical presentations that include impairments in cognition, behavior, and mood, and in some cases, chronic headache and motor and cerebellar dysfunction [14]. Behavioral changes such as irritability, judgment issues, increased risk-taking, and depression are characteristic and prominent early in the disease course. The presence of inflammation during CTE is accompanied by the activation of astrocytes and microglial cells [17]
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