Abstract
Fibroblast growth factor 1 (FGF1) is thought to exert protective and regenerative effects on neurons following spinal cord injury (SCI), although the mechanism of these effects is not well understood. The use of FGF1 as a therapeutic agent is limited by its lack of physicochemical stability and its limited capacity to cross the blood‐spinal cord barrier. Here, we demonstrated that overexpression of FGF1 in spinal cord following SCI significantly reduced tissue loss, protected neurons in the ventricornu, ameliorated pathological morphology of the lesion, dramatically improved tissue recovery via neuroprotection, and promoted axonal regeneration and remyelination both in vivo and in vivo. In addition, the autophagy and the expression levels of PRDX1 (an antioxidant protein) were induced by AAV‐FGF1 in PC12 cells after H2O2 treatment. Furthermore, the autophagy levels were not changed in PRDX1‐suppressing cells that were treated by AAV‐FGF1. Taken together, these results suggest that FGF1 improves functional recovery mainly through inducing PRDX1 expression to increase autophagy and anti‐ROS activity after SCI.
Highlights
Traumatic spinal cord injury (SCI) is a significant contributor to many neurological complications, including paraplegia or quadriplegia
The result showed that the autophagy-associated proteins, ATG7, Beclin[1] and LC3 II/I, were significantly decreased in the Adenoassociated virus (AAV)-Fibroblast growth factor 1 (FGF1) + LV-PRDX1 group compared to the AAV-FGF1 group after exposure to H2O2 (Figure 9A-E)
The vital neuroprotective and neuroregenerative effects of FGF1 may be through the PI3K/Akt and MAPK/ERK pathways.[22,23,24]
Summary
Traumatic spinal cord injury (SCI) is a significant contributor to many neurological complications, including paraplegia or quadriplegia. Considered a multi-factorial and complicated stage that starts after primary SCI and can last weeks or even months.[5] Hypoxia-ischaemia (HI) at the lesion site of the spinal cord, resulting from primary mechanical trauma, affects the production of active oxygen and free radicals (reactive oxygen species, ROS),[6] one of the major detrimental effects during secondary injury.[7,8] Autophagy is an intracellular degradation pathway that delivers cytoplasmic components to the lysosome, and is involved in many essential physiological processes, such as axon formation.[9,10] the dysregulation of autophagy may contribute to numerous pathological conditions.[11] One type of PRDX1 may play a key role in mediation of the interaction between ROS and autophagy
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