The main goal of this project was to test the effectiveness of a novel combination neuroprotection therapy for traumatic brain injury (TBI). TBI affects millions of people worldwide every year. Neuroinflammation, excitotoxicity and neuronal death as well as related mechanisms contribute to the development of acute and complex neurological deficits, including post-traumatic seizures and cognitive dysfunction. Neuroprotection approaches targeting acute and chronic phases of TBI are needed to limit the damage and prevent post-TBI dysfunction. A variety of neuroprotection approaches such as statins, progesterone (P), cyclosporine A and anti-inflammatory agents have been tested that either target neurons or non-neuronal cells in animal models of TBI. Herein we evaluated the neuroprotective potential of the neurosteroid Ganaxolone (GX) in a mouse TBI model. GX is a synthetic neurosteroid related to allopregnanolone that has sedative, anxiolytic, and anticonvulsant effects. To our knowledge GX has not been used as a neuroprotective agent for TBI. We utilized a controlled cortical impact (CCI) model, which simulates aspects of concussions, brain contusions, and hemorrhages seen in human TBI. Our pilot studies showed the feasibility of TBI-induced chronic epilepsy model in mice. Ganaxolone treatment had positive outcomes on motor function and additional promising disease-modifying or protective potential to reduce epileptic seizures. This pilot study will be advanced further in a larger cohort to confirm Ganaxolone's ability to reduce or prevent PTE.
