Role of Fibroblasts in Axon Regeneration after SCI

描述（由申请人提供）：脊髓损伤（SCI）导致瘢痕组织的形成，这是轴突再生的有力障碍。这种疤痕是由啮齿类动物和人类细胞外基质（ECM）分子的过量沉积组成的。为什么大多数轴突不能生长到这个富含ecm的区域还不完全清楚。体外实验表明与成纤维细胞有关

DESCRIPTION (provided by applicant): Spinal cord injury (SCI) results in formation of scar tissue that is a potent barrier to axon regeneration. This scar is comprised of excess deposition of extracellular matrix (ECM) molecules in both rodents and humans. Why most axons fail to grow into this ECM-rich region is not fully understood. In vitro assays have implicated fibroblasts as a major source of inhibitory ECM molecules, but whether this also true in vivo is not clear. While the meninges were thought to be the primary source of fibroblasts after SCI, recent evidence indicates that the perivascular niche could be an alternative source of the scar tissue. The overall goal of this proposal is to determine the role of perivascular fibroblasts in scar formation in order to promote axon regeneration after contusive SCI by pursuing the following aims: 1) Determine the temporospatial distribution and the cellular fate of fibroblasts after contusive SCI 2) Determine the effect of fibroblast ablation on scar formation and axon regeneration after SCI. 3) Determine the role of fibroblast PDGFR-¿ on scar formation and axon regeneration after SCI. Our proposed studies will fill a gap in knowledge about the role of fibroblasts in animal models of SCI and may reveal new therapeutic targets to treat SCI patients.