Systemic Administration of Fibroblast Growth Factor 21 Improves the Recovery of Spinal Cord Injury (SCI) in Rats and Attenuates SCI-Induced Autophagy

Abstract

Protecting the death of nerve cells is an essential tactic for spinal cord injury (SCI) repair. Recent studies show that nerve growth factors can reduce the death of nerve cells and promote the healing of nerve injury. To investigate the conducive effect of fibroblast growth factor 21 (FGF21) on SCI repair. FGF21 proteins were systemically delivered into rat model of SCI via tail vein injection. We found that administration of FGF21 significantly promoted the functional recovery of SCI as assessed by BBB scale and inclined plane test, and attenuated cell death in the injured area by histopathological examination with Nissl staining. This was accompanied with increased expression of NeuN, GAP43 and NF200, and deceased expression of GFAP. Interestingly, FGF21 was found to attenuate the elevated expression level of the autophagy marker LC3-II (microtubules associated protein 1 light chain 3-II) induced by SCI in a dose-dependent manner. These data show that FGF21 promotes the functional recovery of SCI via restraining injury-induced cell autophagy, suggesting that systemic administration of FGF21 could have a therapeutic potential for SCI repair.

Cellular Mechanisms of FGF-Stimulated Tissue Repair

“…For example, a knockout of their co-receptor, Klotho, resulted in delayed skin wound healing in mice and was accompanied by an increased expression of proinflammatory cytokines in wound lesions [ 51 ]. Moreover, the systemic administration of FGF21 attenuated neurodegeneration and neuroinflammation in aged and diabetic mice [ 52 ] and improved the recovery of spinal cord injury in rats [ 53 ]. Finally, Fgf15 −/− mice demonstrated a strongly suppressed ability to regenerate the liver after partial resection [ 54 ].…”

Hypoxia Response Element-Directed Expression of aFGF in Neural Stem Cells Promotes the Recovery of Spinal Cord Injury and Attenuates SCI-Induced Apoptosis

“…AAV is safe and can deliver its single-stranded DNA (ssDNA) vector genome to various tissues and cell types, and can be expressed for a long time (Wang et al, 2019(Wang et al, , 2020. Hypoxia-response element (HRE) is the main regulator of cell response to hypoxia, which can regulate the transcription of specific genes under hypoxia, so it is widely used in the construction of hypoxia-regulated expression genes (Wu et al, 2015;Zhu et al, 2021). In this study, we used AAV with HRE, to induce HRE-mediated expression of aFGF of NSCs in hypoxic environment, which effectively reduced the tumorigenicity and short half-life emulated with direct injection of aFGF.…”

Catalpol as a Component of Rehmannia glutinosa Protects Spinal Cord Injury by Inhibiting Endoplasmic Reticulum Stress-Mediated Neuronal Apoptosis

“…As an axonal membrane protein, GAP43 is involved in the extracellular growth and regeneration of nerve cells in vivo. It is abundantly expressed during the regeneration and development of neurons during injury (Zhu et al, 2020b;Kim et al, 2021). MAP-2 contributes to the building of the neuronal cytoskeleton at every stage of the nervous system (Subbarayan et al, 2020;Zhou et al, 2021).…”