Exploring the Impact of Fibroblast Growth Factor 17 on Functional Recovery and Neuroinflammation in Spinal Cord Injury

Abstract

Spinal cord injury (SCI) affects more than 300,000 people in the United States, making it a significant and widespread problem. This includes injuries at the cervical level, which pose greater challenges due to respiratory in addition to mobility issues. Though there is a large societal impact there is still standard of care following spinal cord injury. While previous preclinical research has shown benefits from FGF1 and FGF2, there is weak data to suggest their clinical effcacy. A related compound, Fibroblast Growth Factor 17 (FGF17), has recently been described as a component within the CSF of young animals that when delivered to aged animals improved cognitive function. These improvements were associated with oligodendrogenesis. Spinal cord injury results in secondary demyelination, which may be mitigated by increasing oligodendrogenesis; this led us to examine how FGF17 may be used as a therapeutic agent following SCI. We used a rat C2 hemisection injury model to evaluate the effects of FGF17 at 4 hours, 2 and 6 weeks after injury. FGF17 was administered via intrathecal infusion at 25 μg/μl for 14 days at 0.5 μL/hour or a single application of 20 μL (4-hour timepoint). Following treatment, whole body plethysmography was performed weekly. Tissues were collected at endpoint to assess brainstem neuroinflammation via immunohistochemistry and molecular signaling pathways via western blotting. As anticipated, animals that were not treated with FGF17 had reduced tidal volume following spinal cord injury. Treatment with FGF17 partially preserved tidal volume as early as 3 days post injury. 6 weeks following spinal cord injury we observed a reduction in GFAP+ and IBA1+ staining in the brainstem near regions associated with respiratory control in animals treated with FGF17. Further, when we quantified the protein content in the spinal cord near the lesion epicenter we saw an increase in p-ERK 1/2 in all injured animals. However, in FGF17 treated animals we saw an increase in downstream transcription factors, STAT6 and Serum Response Factor. Serum Response Factor was implicated in oligodendrogenesis, ongoing studies will directly address this. These data suggest that FGF17 may be a viable alternative to the traditional fibroblast growth factor family members when treating spinal cord injury. R21NS121966, R01NS116068. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.