Grant: Project Grant

An intracerebral hemorrhage (ICH) is a devastating stroke caused by a bleed into the brain. Almost 40% of ICH patients die, many in days. The bleed destroys brain tissue, alters the delicate balance of important ions and water, and takes up valuable space within the skull. This causes pressure to rise. High intracranial pressure (ICP) impairs blood flow to the brain, causing more damage and sometimes death. The body has several natural ways to compensate and help lower ICP. Our animal research has found an additional mechanism. We discovered that cell shrinkage (CS) occurs in areas located away from the damaged tissue. Some cell bodies shrink by up to 50%. This means that those parts of the brain become a bit smaller. This frees up space within the skull and limits the rise in ICP. While this helps reduce the risk of death, it still commonly occurs after very large ICHs. Thus, we need to do more to treat high ICP. Our research will study patients who died from a large ICH. Using their brain tissue, we will look for whether CS occurs in humans, if there are any harmful effects, and we will examine how CS occurs. Concurrently, we will use rat models of severe ICH to determine how age, hypertension and ICP control therapies affect CS in male and female rats. These are clinically important factors that we will incorporate into our research to improve the validity of our animal studies (e.g., to explain the negative impact of hypertension). We will also look to better document how CS affects neuronal health and function. Finally, we will examine rat and human tissue to determine the mechanisms underlying CS. For example, we know that movement of potassium, chloride and water across a cell membrane is very important to cell size, and so we will study these and other mechanisms. Eventually, we hope to safely manipulate CS to improve the medical management of high ICP after large strokes and other brain injuries, thereby improving survival and recovery.