Poster abstracts
Poster number 80 submitted by Jamie Church
Altered immune signaling impairs oligodendrocyte lineage cell responses and functional recovery after spinal cord injury in mice
Jamie Church (Neuroscience Graduate Program), Phillip Popovich (Neuroscience, Ohio State University), Dana McTigue (Neuroscience, Ohio State University)
Abstract:
Prominent oligodendrocyte (OL) loss occurs after spinal cord injury (SCI), followed by a rebound in the first 2 weeks post-injury due to proliferation and differentiation of surviving OL progenitor cells (OPCs). The mechanisms controlling this endogenous response, however, are not understood. Previous work from our group showed activation of toll-like receptor 4 (TLR4) on microglia induced OPC proliferation and oligodendrogenesis in the intact spinal cord. Since TLR4 ligands are present in the injured spinal cord, we tested the hypothesis that TLR4 signaling contributes to oligodendrogenesis after SCI. Wild-type (WT) and TLR4-deficient (TLR4d) mice were given a midthoracic moderate contusion SCI and sacrificed for spinal cord histology and PCR at 1, 3, 7, 14, or 21d post-injury; behavioral analyses and axon and myelin integrity analyses were conducted on a separate set of animals surviving up to 42d. Reduced locomotor recovery in TLR4d mice coincided with reduced OL lineage cell responses and less spared tissue chronically in ventral motor tract areas. TLR4d mice had increased OL loss acutely concurrent with decreased ferritin (iron storage) expression in the lesion, suggesting TLR4 signaling helps protect against acute iron-mediated damage. TLR4d mice had reduced OL numbers and OPC markers chronically despite enhanced acute OPC proliferation. Inhibitors of OL differentiation were increased in TLR4d mice, likely promoting lower chronic OL numbers. Additionally, delayed lipid accumulation (debris phagocytosis) in TLR4d mice could contribute to reduced OPC and OL responses. Interestingly, growth factor expression was elevated, suggesting that TLR4 signaling normally suppresses growth factor expression after SCI. Collectively, this work shows that post-SCI OL protection and replacement are influenced by the inflammatory environment, and highlights the importance of TLR4 signaling for normal cellular repair mechanisms, growth factor expression, and functional recovery.
Keywords: TLR4, Spinal cord injury, oligodendrocyte