IL‐6 mediates impaired motor coordination but not cognition in a murine model of mild traumatic brain injury (mTBI)

Abstract

Mild traumatic brain injury (mTBI) affects more than 1.7 million people in the United States annually. mTBI is difficult to diagnose and is clinically associated with impaired motor coordination and cognition. To evaluate and define the deficits after TBI a murine model was used. mTBI was induced by weight drop (400g; 1.5cm). Mice were evaluated for motor coordination by rotarod and cognition by novel object recognition. Cytokine analysis on serum and brain samples was done by ELISA. Neuron specific enolase (NSE) and glial fibrillary acidic protein (GFAP) were brain injury markers. Blood brain barrier (BBB) disruption was evaluated using fluorescent micromolecular and macromolecular molecules. Experiments were repeated after giving anti‐IL‐6 antibody systemically after mTBI. mTBI induced deficits in motor coordination and cognition compared to controls. mTBI resulted in increased serum IL‐6, NSE and GFAP, decreased cognition, and decreased motor coordination. In addition, mTBI caused slight BBB breakdown; allowing micromolecular, but not macromolecular leakage. Neutralization of IL‐6 with antibody significantly improved motor coordination, but not cognition, after mTBI. The data suggest that IL‐6 is induced by mTBI and that blockade of IL‐6 mitigates mTBI‐induced motor coordination deficit.