Pilot: Metabolic Regulation of Reactive Astrocytes After SCI

Astrocytes are critical modifiers of central nervous system (CNS) pathophysiology. They react to CNS damage with a range of response broadly referred to as astrogliosis. Focal trauma to the CNS, including spinal cord injury (SCI), results in scar-forming astrogliosis at the site of injury that limits the spread of inflammatory cells, thereby facilitating wound healing in the sub-acute phase of injury. Understanding how astrocytic scar formation is regulated is important to selectively harnessing neuroprotective effects of reactive astrocytes. While we and others have contributed to the identification of cytokine and cellular stress signaling pathways to the regulation of astrogliosis, current understanding of metabolic control of astrogliosis is surprisingly rudimentary, especially given that astrocytic scar formation is a high energy demanding process. Using a genetic model that enhances scar-forming astrogliosis after SCI, we identified astrocytic glycogen – an energy reserve of the CNS – as a candidate metabolic regulator of astrogliosis. This project tests the hypothesis that SCI increases metabolism of astrocytic glycogen to provide bioenergetic substrates that fuel astrocyte-mediated wound healing. Leveraging my expertise of astrocyte biology in spinal cord repair and state-of-the-art technology for metabolic analyses offered by CNS-Met COBRE Cores, completion of this project is expected to advance fundamental knowledge of metabolic control of reactive astrocytes and identify novel metabolic targets of intervention to promote neural repair.