Grant: Project Grant

Multiple Sclerosis is a chronic autoimmune disease with unknown cause. As people living with MS (pwMS) age, they exhibit progressively worsened disability. This progressive worsening is thought to be driven by a pathological process whereby grey matter in the brain is injured. The mechanism(s) that drive grey matter injury is not understood, and we have no effective treatments to stop it. Genetics cannot fully explain MS risk and progression - environmental factors can significantly contribute to disease development. One potential risk factor is concussion, although its association with MS has been seen in some, but not all studies. Importantly, concussion has been shown to impact a part of the brain - the meninges - that plays host to immune cells during MS. Importantly, presence of immune cells in the meninges during MS is associated with grey matter injury. To disentangle whether concussion is truly associated with MS risk, animal models are needed. To this end, we have developed a mouse model of concussion as well as a model of grey matter injury like what is observed in MS. Combining these 2 mouse models together provides us with an opportunity to ascertain potential connections between MS and concussion. Using cerebral spinal fluid from MS patients, we will confirm our mouse model findings in the human disease. Collectively our proposed experiments will allow us to learn whether concussion can increase risk of developing grey matter injury in MS patients and will provide insights into the mechanisms for how this may occur.