Grant: Project Grant

Concussions are a form of mild traumatic brain injury (mTBI), often called the "unseen injury", because of the lack of obvious damage. As a result, many individuals suffer repeated concussions, often in short time spans. In some sports, like hockey and football, awareness is growing that repeated sub-concussive blows to the head are routinely incurred in practices and games. Although many of these impacts do not result in a diagnosis of concussion, there is a growing appreciation that both concussions and sub-concussive impacts can negatively impact cognitive function in the developing brain, and that repeated concussions (r-mTBI) can have long-term detrimental effects for cognition in elderly populations. Despite these concerns, few laboratories have systematically studied r-mTBI in a preclinical model that properly mimics the human condition. We have recently developed a model that enables us to accurately examine r-mTBI and understand how the brain responds to repeated mTBI. Because significant structural damage does not occur in mTBI, our focus is on whether there is damage to small blood vessels in the brain. These vessels are below the threshold of resolution for magnetic resonance imaging, but can be resolved using high resolution microscopy. When damaged, these vessels can release a compound in the blood called fibrinogen. Fibrinogen is normally important for clotting, but can also initiate an inflammatory process involving brain microglia that negatively impacts neurons, and impairs learning and memory processes. The results of the proposed work will help us to better understand the mechanisms involved in mTBI; how they directly impact brain function, and increase our understanding of how r-mTBI early in life could negatively impact individuals as they age. More importantly, this work will enable us to determine the therapeutic value of modulating fibrinogen's effects in the brain to help reduce the negative impact of r-mTBI on cognition.