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Updated: Mar 2, 2026
A Repetitive Concussive Head Injury Model in Mice
Published on: October 12, 2016
Clinical correlates to assist with chronic traumatic encephalopathy diagnosis: Insights from a novel rodent repeat
Gretchen M Thomsen1, Ara Ko, Megan Y Harada
1From the Regenerative Medicine Institute (G.M.T., A.M., L.W., P.H., N.C., O.S.), Department of Biomedical Sciences (G.M.T., J-P.V.), and Biobehavioral Research Core (J-P.V.), and Division of Trauma and Critical Care, Department of Surgery (A.K., M.Y.H., N.D., E.J.L.), Cedars-Sinai Medical Center, Los Angeles, California.
Introduction:
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to repetitive head injuries. Chronic traumatic encephalopathy symptoms include changes in mood, behavior, cognition, and motor function; however, CTE is currently diagnosed only postmortem. 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 wild-type rats; eight rats received two injuries (2×TBI), 27 rats received five injuries (5×TBI), 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, and inflammation were assessed.
Results:
All eight 2×TBI cases had mild rotarod deficiency, 11 5×TBI cases had mild deficiency, and 16 cases had severe deficiency. In one cohort of rats, tested at approximately 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, phosphorylated 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.
Conclusions:
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.
