Analysis of markerless limb tracking reveals chronic and progressive motor deficits after a single closed head injury in mice

Abstract

Background: Acute injury following brain trauma may evolve into a chronic and progressive disorder. Assessment of chronic consequences of TBI must distinguish between effects of age and injury. Methods: C57BL/6 mice receive single closed head injury (CHI) and are analyzed at 14DPI or 180DPI for cortical atrophy and 7DPI or 180DPI for behavioral outcomes. Results: CHI induces ipsilesional atrophy at 14DPI that increases 180 DPI due to an effect of age. On open field, injured mice develop a turn bias at 180DPI not present at 7DPI. On rotarod, injured mice have shorter latencies at 7DPI, but not at 180DPI due to worsening performance of aging uninjured mice. On beam walk, both groups at 180DPI more slowly traverse a 2cm and 1cm beam than at 7DPI. Foot-faults show no significant effects of age or injury. Limb position was assessed using DeeplabcutTM markerless tracking followed by computation of absition (integral of limb displacement over time) using custom Python scripts. On the 2cm beam, age increased absition in all limbs of uninjured mice and both forelimbs of injured mice. Injury increased left hindlimb absition at 7DPI. On the 1cm beam both forelimbs and the left hindlimb of injured mice at 180DPI have larger absition than uninjured mice at 180DPI or injured mice at 7DPI. These data suggest chronic and progressive motor deficits of injured mice at 180DPI. Conclusions: A single impact produces ipsilesional cortical atrophy and chronic and progressive motor deficits. Quantitative behavioral analysis reveals deficits not seen using standard outcomes.