Functional Diversity of Reactive Astrocytes in Spinal Cord Repair

ABSTRACT This project interrogates the regulation and functions of scar-forming astrogliosis at the chronic lesion versus diffuse astrogliosis in the degenerating axonal tracts following SCI. We will distinguish these two types of astrogliosis based on their spatial separation in the injured spinal cord, our use of distinct SCI models, and different outcome measures. We will genetically manipulate the level of astrogliosis in LZK mutant mice, and assess LZK-CSF1 as a common mechanism underlying the distinct functions of scar-forming versus diffuse astrogliosis. Specifically, Aim 1 determines the role of scar-forming astrocytes in pathological retention of macrophages at the chronic SCI scar. Aim 2 examines the role of diffuse astrogliosis in promoting axon sprouting distal to the lesion. Aim 3 assesses the therapeutic potential of AAV-mediated local targeting of either scar-forming or diffuse astrogliosis to promote neural repair after SCI.