Examining sex as a predictor of outcome across mulitple levels of head trauma

Albert Einstein College Of Medicine, Inc, Bronx NY

Investigators

Abstract

! Abstract: Mild traumatic brain injury (mTBI) or concussion is common in contact sports. It is estimated that 1.6-3.8 million sports-related mTBIs occur every year. While most who suffer an mTBI recover fully in a matter of days to weeks, some suffer long term sequelae that can last years. While American football is the leading cause of sports-related concussion, soccer is the most popular sport in the world and the most frequent cause of sports-related concussion in women. The effects of mTBI in women may be particularly important, as women have reported both worse and longer lasting symptoms following mTBI than men. Soccer is also unique in that it is the only sport where the head is used intentionally deflect the ball, termed heading. Although not a common cause of concussion, a soccer player can amass hundreds to thousands of headers, or subconcussive impacts, over the course of a season. Recently, mTBI and repetitive subconcussive injury have come under increased scrutiny because a growing number of athletes with histories of repetitive head trauma have developed a newly described tauopathy, termed chronic traumatic encephalopathy (CTE). CTE is a neurodegenerative disease characterized by changes in behavior and cognition, with a distinct pattern of tau deposition that can only be diagnosed post-mortem. However, it is currently unclear to what extent mTBI and/or repetitive subconcussive head injury contribute to disease, and what mechanisms underlie disease progression. Additionally, identifying susceptibility and risk factors remains an elusive goal. Animal models are required to bridge the gap between clinical neuroimaging findings and cellular mechanisms of injury progression and repair. Here we propose to use a closed head injury (CHI) model to examine sex differences in outcome at two levels of head injury; the first being mTBI, and the second repetitive subconcussive injury. Animals will be evaluated with in vivo diffusion tensor imaging (DTI), behavior, and post-mortem pathology. With these two models, we seek to determine how hormonal differences across sex affect injury severity and recovery across each level of head trauma. To complete these goals, I propose two aims: 1) Test that timing within the estrous cycle affects outcome after mTBI, and 2) Test the role of sex on outcome following repetitive subconcussive injury. At the conclusion of these aims we will have filled in an important gap in knowledge regarding sex and how it relates to susceptibility to brain injury. Additionally, we will provide new information about the importance of impact number versus severity on long-term outcomes. In carrying out these experiments, I will receive valuable training in animal imaging, behavior, and histopathology toward a career as a physician scientist.