FGF10 Attenuates Experimental Traumatic Brain Injury through TLR4/MyD88/NF-κB Pathway

Traumatic brain injury (TBI) can induce neuronal apoptosis and neuroinflammation, resulting in substantial neuronal damage and behavioral disorders. Fibroblast growth factors (FGFs) have been shown to be critical mediators in tissue repair. However, the role of FGF10 in experimental TBI remains unknown. In this study, mice with TBI were established via weight-loss model and validated by increase of modified neurological severity scores (mNSS) and brain water content. Secondly, FGF10 levels were elevated in mice after TBI, whereas intraventricular injection of Ad-FGF10 decreased mNSS score and brain water content, indicating the remittance of neurological deficit and cerebral edema in TBI mice. In addition, neuronal damage could also be ameliorated by stereotactic injection of Ad-FGF10. Overexpression of FGF10 increased protein expression of Bcl-2, while it decreased Bax and cleaved caspase-3/PARP, and improved neuronal apoptosis in TBI mice. In addition, Ad-FGF10 relieved neuroinflammation induced by TBI and significantly reduced the level of interleukin 1 beta/6, tumor necrosis factor alpha, and monocyte chemoattractant protein-1. Moreover, Ad-FGF10 injection decreased the protein expression level of Toll-like receptor 4 (TLR4), MyD88, and phosphorylation of NF-kappa B (p-NF-kappa B), suggesting the inactivation of the TLR4/MyD88/NF-kappa B pathway. In conclusion, overexpression of FGF10 could ameliorate neurological deficit, neuronal apoptosis, and neuroinflammation through inhibition of the TLR4/MyD88/NF-kappa B pathway, providing a potential therapeutic strategy for brain injury in the future. (c) 2021 S. Karger AG, Basel

Automated summary

The overexpression of FGF10 can alleviate neurological deficits, neuronal apoptosis, and neuroinflammation in experimental TBI mice by inhibiting the TLR4/MyD88/NF-kappa B pathway, providing a potential therapeutic strategy for brain injury.