Grant: Project Grant

Each year, approximately 165,000 Canadians suffer traumatic brain injury (TBI) and more than 10% of these individuals require costly hospitalization. The severity of non-lethal TBI can range from mild (e.g. concussions) to severe (e.g. irreversible coma) depending on the duration of the loss of consciousness, degree of temporary cognitive deficits, and presence or absence of physical damage detectable by CT scan. However, TBI is not only associated with cognitive/motor dysfunction. A wide variety of other symptoms can emerge due to the effects of head injury on the hypothalamus, a part of the brain which automatically regulates homeostatic functions such as body temperature, hunger, body fluid balance and circadian rhythms. Notably, a high fraction of TBI patients develop delayed hyponatremia, a condition in which blood sodium levels are abnormally low, which can cause brain swelling and death if not treated with urgency. This condition can present itself many hours after (or day after) the TBI. This can be problematic (dangerous) if the patient has been released from the emergency room because they have no visible damage on the CT scan and appear to be otherwise asymptomatic. The homeostatic deficits associated with TBI are poorly understood. In this project we will use a mouse model of mild TBI that recapitulates many of the symptoms of human mild TBI, including delayed hyponatremia, hypothermia and disruption of circadian rhythms. Our experiments are designed to provide a mechanistic explanation for the development of these symptoms following mild TBI and provide important insight into how the time of day at which a TBI is received can affect the timing of circadian rhythms. The results could also lead to the development of a diagnostic test to identify patients which are at risk of developing delayed hyponatremia, and how to treat this condition when it arises.