Obesity-induced Brain Insulin Resistance Exacerbates TBI Outcome

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Date

2015-05

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The Ohio State University

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Abstract

Traumatic brain injury (TBI) hospitalizes 1.7 million Americans every year and puts patients at risk for many complications including brain swelling, stroke, and behavioral, emotional and cognitive deficits. A common consequence of TBI is increased energy demand in the brain following injury, a phenomenon that has been attributed to a need to counteract the physical damage of impact. Our data suggest 1) that this compensatory mechanism is impaired when multiple TBIs occur close together in time, and 2) that this effect is driven by brain insulin resistance. The purpose of this study is to examine whether systemic insulin resistance prior to TBI (i.e. a model of type 2 diabetes) would further exacerbate TBI outcome. We used a diet-induced obesity model to create obese (intended to be insulin resistant) and lean cohorts of mice. Mice from both groups were randomly assigned to either a sham-injury procedure or two mild traumatic brain injuries (mTBI) 24 hours apart. Behavioral tests were used to assess anxiety-like behavior, motor coordination, and spatial learning/memory. Analysis of the brains indicated insulin resistance in both injured animals and diet-induced obese animals. Both diet-induced obesity and injury were correlated with greater cognitive deficits. These data support insulin insensitivity as a potential causal mechanism driving cognitive impairment in TBI. If this causal relationship among TBI and insulin resistance and cognitive deficits is established, then this work could conceivably lead to the treatment of TBI patients with insulin sensitizing drugs in order to reduce the severity of deficits.

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Traumatic brain injury, Insulin resistance, Obesity, Cognitive deficits, anxiety, metabolism

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