Grant: Foundation Grant

The goal of my research is to prevent neuronal death and brain impairment that occurs following stroke and during neurodegeneration. My work in the past has shown that the preservation of a healthy brain requires communication between the nerve cells and the surrounding cells termed glia, such as astrocytes and microglia. My research will show how glia respond to brain diseases and traumatic damage and how they aid in recovery. The major cause of patient mortality after stroke or brain injury is brain swelling called brain edema. We have found a new pathway allowing chloride to enter nerve cells that leads to increased water entry into neurons. We will determine how to block chloride entry and brain swelling in nerve cells and we will investigate the contributions of glia to the control of chloride entry into neurons and brain swelling. The goal is to discover the triggers that cause brain swelling and how therapeutic compounds could block brain edema to reduce brain damage and patient mortality. One type of glia, called microglia are the immune cells of the brain and respond to infections and to damage by repairing surrounding tissue and removing debris. Sometimes however microglia can themselves cause damage and brain impairment. We will determine the factors that cause microglia to switch from protecting the brain to releasing factors to cause damage or impair brain function. This will guide us in developing drugs to prevent microglia-induced damage. The brain is the most metabolically active region of the body and requires a constant supply of oxygen and glucose (sugar) via the blood via processes regulated by astrocytes, another glial cell. Experiments will be undertaken to carefully determine the conditions under which astrocytes regulate neuronal activity and cerebral blood flow in normal brains and in conditions of neurodegeneration such as Alzheimer's. This work will guide the development of new therapies to maintain brain health.