Grant: Operating Grant

Swelling of the brain, termed brain edema, has terrible consequences for patients. Large strokes that affect substantial regions of the brain, head injury, hypoxia or infection can lead to brain edema. The swelling of the brain under these circumstances can progressively develop leading to increased pressure inside the skull, coma and even death. The treatments available for preventing brain edema are very limited and in extreme cases involve removing the overlying bones of the skull to allow brain swelling to occur without increasing intracranial pressure. New treatments for limiting brain swelling could have profound therapeutic impact. Brain edema is a major cause of mortality from large area strokes. Understanding how brain edema develops and what processes or ion channels that if blocked could prevent it will provide a critical mechanism to prevent this major cause of death after strokes. The research proposed here will examine the cellular mechanisms that contribute to brain edema and the progressive death of neurons. In the intact skull the immediate cause of death from brain edema is the herniation of the brain into the brainstem. Prevention of neuronal swelling is one avenue to reduce overall brain swelling and prevent herniation. However neuronal swelling itself can lead to the death and disruption of neurons and breakdown of neuronal connectivity. This research is designed to determine whether a type of channel in neurons called a pannexin channel contributes to the disruption and death of neurons during swelling. Success will lead to new therapies to prevent brain damage from edema.