MENINGEAL AND NEUROVASCULAR RESPONSES TO BLAST-INDUCED AFTER TRAUMATIC BRAIN INJURY

The goal of this project is to further our understanding of the subtle changes in cerebral protection that occur after the brain sustains a blast injury. Under healthy circumstances, the brain is protected by a system of “barriers”, such as the “blood-brain barrier” as well as by meningeal coverings that surround the outside of the brain. However, researchers have shown in patients and in animal models that blast exposure at least temporarily “opens” these barriers, allowing foreign molecules and cells to enter the brain. These molecules and cells then can cause inflammation in the brain, as well as the release of chemicals that damage brain tissue. The process can be damaging to the brain and possibly leave it in a state of constant low-grade inflammation. Inflammation of the brain has been associated with certain neurodegenerative diseases, including Alzheimer disease, Parkinson’s disease and Huntington’s disease. In cases where blast brain injury is considered mild, the consequences may cause a slow or delayed effect on thinking and behavior, and contribute to the neurodegenerative diseases just mentioned. Blast-related brain inflammation is considered important, but there is much we do not know about the specific mechanisms for how this unfolds. In this project, mice will be anesthetized and exposed to blast waves. The mice will then be humanely euthanized to retrieve samples of the meninges (the covering of the brain) and the brain to study alterations in immune system-related molecules and cells that are recruited during tissue injury. We hope to demonstrate the time course of meningeal disruption and the opening of the blood-brain barrier is associated with the activation of inflammatory processes in these structure. A second goal will be to test a certain compound that may reduce the actions of these invading molecules and cells, to thus reduce the level of brain inflammation caused by blast exposure. This compound, or related reagents, may help to identify classes of drugs that could be used for the treatment of blast-related traumatic brain injury.