MODULATION OF NF-KB-DEPENDENT IMMUNE RESPONSES FOR POST-TBI NEUROREGENERATION

The injury-stimulated inflammatory response has evolved to promote tissue repair and functional recovery. However, it is clear that not every inflammatory response is beneficial. In the context of the CNS, certain repair responses stimulated by the inflammatory response, such as glial scarring, lead to replacement of CNS tissue with astrocytes and connective tissue, actively inhibiting CNS repair processes. In contrast, increasing evidence indicates that immune cells in the CNS, particularly T cells, may promote the properly targeted migration and engraftment of endogenous neural stem cells, thereby promoting regenerative responses. Our project is designed to better define cellular and molecular mechanisms of the inflammatory response to TBI. We hypothesize that NF-¿B-dependent immune responses are a major determinant of functional recovery, post-TBI. Our goal is to define the contribution of specific NF-¿B signaling pathways and NF-¿B-dependent immune mechanisms to TBI outcome. Specifically, we are performing experiments to characterize the cellular and molecular components of the post-TBI immune response, to determine how TBI outcomes are influenced by MyD88- and NF-¿B-dependent inflammatory responses, and to elucidate the role of NF-¿B dependent T cell responses in determining TBI outcomes. We expect that the data generated in this project will be crucial in assembling a mechanistic understanding of TBI-induced and immune response-mediated loss of CNS function, and for efforts to develop effective treatments and therapies for TBI.