Grant: Project Grant

Traumatic brain injury (TBI) is a life-threatening event associated with a major socioeconomic burden. In addition to neurological deficits, it can lead to long-term neuropsychiatric co-morbidity, cognitive impairment, and be a risk factor for the development of Alzheimer's disease. There is currently a paucity of effective treatments to improve memory deficits, neuropsychiatric disorders and mitigate neuropathological hallmarks of TBI. Deep brain stimulation (DBS) involves the delivery of electrical current to the brain through implanted wires called electrodes. It is an established therapy to treat movement disorders, such as Parkinson's disease and tremor, and has been recently approved for the treatment of epilepsy and obsessive-compulsive disorder. To date, DBS has been mainly used as a symptomatic treatment and not to halt the progression of disease states. We have recently found that DBS may reduce brain inflammation and increase levels of substances called trophic factors. These aspects suggest that DBS may have the potential of mitigating memory deficits, neuropsychiatric problems and neuropathology after traumatic brain injury. Another recently proposed treatment for neurological and psychiatric disorders is focused ultrasound (FUS). This consists of the emission of multiple ultrasonic beams to a single point to create brain lesions or to focally deliver drugs into the brain. The latter can be done when drugs are loaded into small particles called droplets, which burst and release their content when in contact with the ultrasound. In this study we will test whether DBS or drug-loaded droplets administered during FUS improve memory performance, anxiety and are neuroprotective in a rodent model of TBI. This work will be quite novel, as it will be the first to test whether treatments that alter brain function (DBS and FUS) may be used to improve TBI-induced neurodegeneration and memory deficits.