PDGF-B, but not PDGF-D, prevents spinal cord injury-induced cavitation in rats via fibroblast recruitment and extracellular matrix remodeling

Background: Spinal cord injury (SCI) induces substantial cell loss at the injury site, leading to the formation of cystic cavities, a major obstacle to neural repair in both humans and rats. The mechanisms driving cavity development remain elusive. Given the well-established role of platelet-derived growth factor-B (PDGF-B) in wound healing via activation of its receptor PDGFR-β, as demonstrated in mice, we propose that impaired PDGFR-β signaling may be a key contributor to cavity formation post-SCI in rats. Methods: First, the spatiotemporal expression patterns of PDGF-B, PDGF-D, PDGFR-β, and key extracellular matrix (ECM) components (Fibronectin, Laminin, Collagen I) were assessed in rat spinal cord following crush injury using immunofluorescence, and the process of cavity formation was observed. Subsequently, the therapeutic potential of immediate and delayed in situ delivery of PDGF-B, PDGF-D, or Fibronectin on post-traumatic cavitation were evaluated. Additionally, the necessity of fibroblast activation and recruitment was assessed by intraperitoneal administration of the PDGFR-β inhibitor SU16f. Results: Expression of PDGFR-β, Fibronectin, laminin, and collagen I peaked at 7 days post-injury (dpi) and subsequently regressed within GFAP-negative regions, coinciding with progressive cystic cavity formation by 28 and 56 dpi in the injured rat spinal cord. Endogenous PDGF-D peaked at 3 dpi, while PDGF-B peaked at 14 dpi, both exhibiting lower levels thereafter. Immediate or delayed in situ injection of exogenous PDGF-B, but not PDGF-D, specifically prevented and reversed cavitation, upon PDGFRβ-mediated fibroblast recruitment and ECM deposition, especially Fibronectin upregulation, thereby yielding marked neurological and motor function recovery following SCI in rats. Fibronectin injection recapitulated the benefits of PDGF-B, whereas systemic SU16f abolished the therapeutic effects of both PDGF-B and Fibronectin. Conclusion: Our findings demonstrate that PDGF-B specifically prevents SCI-induced cavitation in rats by orchestrating fibroblast recruitment and ECM remodeling, providing a translational framework for growth factor therapy after SCI.