Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Traumatic brain injury (TBI) is a serious public health concern and a major cause of disability. It is increasingly being recognized that patients with a TBI have a propensity to develop hyponatremia, also known as a low sodium concentration in the blood. Since sodium is the major ion in the blood, a drop in sodium often equates to a decrease in blood plasma solute concentration (hypo-osmolality). This is a serious condition because as plasma osmolality drops, the osmotic gradient between the blood and the brain is shifted to promote the passage of water into the cells of the brain. This causes swelling of the brain and further exacerbates the initial trauma. However, it is unclear how TBI induces hyponatremia. An important homeostatic mechanism that maintains plasma osmolality in a stable range is the regulation of anti-diuretic hormone (ADH) secretion by the central nervous system (CNS). The neurons in the supraoptic nucleus (SON) of the hypothalamus are specialized to sense changes in plasma osmolality and consequently regulate the release of ADH into the circulation. We hypothesize that TBI induces a failure in this mechanism to promote inappropriate ADH secretion and water retention. The ADH SON neurons are inherently mechanosensitive and mechanical perturbations can increase their ADH secretion. Therefore, we hypothesize that the force of the TBI activates these neurons to induce ADH secretion independent of the plasma osmolality. Indeed, our preliminary data suggest that these neurons are strongly activated following TBI. I will investigate the cellular, molecular, and neural circuit mechanisms underlying the mechanical activation of ADH SON neurons following TBI. Furthermore, I will investigate whether inhibition of these neurons prevents TBI-induced hyponatremia. Understanding the mechanisms by which TBI can cause hyponatremia will aid in the development of therapeutic treatments for this condition.