Graded Mild Head Injury as a Model for Sports Injury

Purpose: To develop a graded model of mild head injury that produces graded behavioral deficits in the mouse. This model will be used to test neuroprotective effects of novel compounds. This study was designed to determine the severity of injury required to cause different behavioral deficits in motor function and cognition. Methods: Young adult male C56/B6J mice were anesthetized daily with isoflurane (20 sec) and 15 sec later were subjected to a weight drop head injury using a tethered steel bar (43 grams) dropped through an acrylic tube from a height of 28 inches. Mice were placed prone on a scored aluminum foil stage 2 cm below the end of the tube. The blow was directed to a 5 mm midline area of the head rostral to the aural canals. The blow causes a break in the scored aluminum foil and allows the mouse to flip 180 degrees and land supine on a foam cushion. This model was chosen to model a hit to the head followed by rotational acceleration indicative of closed head injuries occurring in contact sports. Five groups of mice were randomized to receive 0, 5, 10, 15, 20, or 25 blows, 1 per day M-F. Five days after the final hit, mice then underwent cognitive and behavioral testing consisting of an accelerating Rotorod, Morris water maze, and active avoidance T-maze. Following testing brains will be examined for cell death and inflammation. Results: A total of 30 mice (5 per group) were used for this study. Body weight did not differ among the groups over the course of the study, however waking time after anesthesia was increased in all groups subjected to injury compared to mice anesthetized and not injured. Coordinated movement on an accelerating Rotorod revealed a linear trend for decreased performance with increasing number of head impacts suggesting that a graded approach is possible with this model. Time to fall was significantly shorter than controls at 15 and 25 hits. Water maze and T-maze tests are ongoing. Conclusions: These data suggest that a graded injury regimen can lead to graded behavioral responses in the young male mouse and will provide a useful model for testing the effectiveness of neuroprotective compounds that have the potential to be used as prophylactic agents for those involved in contact sports.