FGF17-Mediated Pathways: Targeting FGFR3 and FGFR4 for neuroinflammation and myelination in spinal cord injury

Spinal cord injury affects more than 300,000 people in the United States. A large portion of these injuries are at the cervical level and pose greater challenges to limb and respiratory function. Demyelination and neuroinflammation contribute to secondary injury cascades further impairing recovery. The fibroblast growth factor (FGF) family has shown promise in improving function following spinal cord injury, particularly FGF1 and FGF2. However, FGF1 and FGF2 are implicated in neural regeneration rather than focusing on glia. Though, emerging evidence suggests that other members of the FGF family, including FGF17, may play a significant role in promoting myelination, and reducing neuroinflammation. Despite its potential, the effects of FGF17 on spinal cord injury recovery remain largely unexplored, highlighting the importance of further investigation into its therapeutic applications. FGF17 has a higher affinity for FGF receptors 3 and 4 but there is not much known regarding where they are expressed. Thus, with this project we sought to evaluate the cellular distribution of these receptors and how that expression pattern changes following spinal cord injury. We used a rat C4 contusion injury model and harvested tissue at 7 days post-injury. Tissue was stained for markers of FGFR3, FGFR4, oligodendrocytes (O4), astrocytes (GFAP), and neurons (NeuN), to assess localization and presence of FGF17 receptors as well as the potential effects on myelination and inflammation following spinal cord injury. Data analysis showed increased colocalization of FGFR4 on astrocytes as well as FGFR3 on oligodendrocytes in contused animals. These findings suggest that FGF17 may act on these glial receptors to influence recovery pathways, such as enhancing myelination and reducing inflammation. Future studies leveraging FGF17 could further clarify its therapeutic potential in SCI recovery. Kentucky Spinal Cord & Head Injury Research Trust (WJA), Craig H. Neilsen Foundation Fellowship (MDS), UK Office of Biomedical Education Undergraduate Research Award (CED) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.