Clinical correlates to assist with CTE diagnosis: Insights from a novel rodent repeat concussion model.

Introduction: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to repetitive head injuries. CTE symptoms include changes in mood, behavior, cognition and motor function, however CTE is only currently diagnosed post-mortem. Using a rat model of recurrent traumatic brain injury (TBI) we demonstrate rodent deficits that predict the severity of CTE-like brain pathology. Methods: Bilateral, closed skull, mild TBI was administered once per week to 35 WT rats, 8 rats received 2 injuries ('2xTBI'), 27 rats received 5 injuries ('5xTBI') and 13 rats were sham controls. To determine clinical correlates for CTE diagnosis, TBI rats were separated based on the severity of rotarod deficits and classified as "mild" or "severe" and further separated into "acute", "short" and "long" based on age at euthanasia (90, 144 and 235 days, respectively). Brain atrophy, phosphorylated tau (p-tau), and inflammation were assessed. Results: All eight 2xTBI had mild rotorod deficiency, 11 5xTBI had mild deficiency and 16 had severe. In one cohort of rats, tested at ~235 days of age, balance, rearing, and grip strength were significantly worse in the severe group relative to both sham and mild groups. At the acute time period, cortical thinning, p-tau and inflammation were not observed in either TBI group, whereas corpus callosum thinning was observed in both TBI groups. At later time points, atrophy, tau pathology and inflammation were increased in mild and severe TBI groups in the cortex and corpus callosum, relative to sham controls. These injury effects were exacerbated over time in the severe TBI group in the corpus callosum. Conclusion: Our model of repeat mild TBI suggests that permanent deficits in specific motor function tests correlate with CTE-like brain pathology. Assessing balance and motor coordination over time may predict CTE diagnosis. (C) 2017 Lippincott Williams & Wilkins, Inc.

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