Ferulic acid produces neuroprotection against radiation-induced neuroinflammation by affecting NLRP3 inflammasome activation. (2nd September 2022) - Liu, Guifang
Abstract: Purpose: After radiation therapy of brain tumors, radiation-induced cognitive impairment is a common and severe complication. Neuroinflammation mediated by microglia is a critical event that accelerates cognitive or functional decline. Ferulic acid (FA), a phenolic plant component, possesses multiple pharmacological effects, such as anti-inflammatory and anti-radiation. The current research attempts to ascertain the protection of FA on radiation-induced neuroinflammation and the mechanism of this effect. Materials and methods: C57BL/6 mice were irradiated with 60 Co γ-ray to establish a brain injury model. The Morris water maze experiment was used to observe the effects of FA on the spatial learning and memory impairment of irradiated mice. The pathological changes of hippocampal tissue were observed by HE staining. Besides, microglia BV-2 cell lines were used to study the anti-neuroinflammatory impacts of FA on radiation-induced microglial activation and further elucidate the potential mechanisms influencing FA-mediated neuroprotective properties. The cell morphological changes were observed using an optical microscope. The cytotoxicity of FA and radiation to BV-2 cells was determined using the CCK-8 assay. Additionally, Western blot and quantitative real-time PCR detected the expression and transcription of NLRP3 inflammasome and pro-inflammatory cytokines in hippocampus and BV-2 cells. Results: FA could enhance learning and memory capacity and ameliorate pathological changes in the hippocampal tissues of irradiated mice. The cell radiation injury model was established by 8 Gy 60 Co γ-ray, and the concentration of subsequent administration was determined to be 2.5, 5, and 10 μmol/L. Furthermore, FA could suppress the transcription and expression of NLRP3 in hippocampal tissue and microglia, and also the increased secretion of pro-inflammatory factors. Conclusion: This study established that FA targeting the NLRP3 inflammasome has a neuroprotective effect against radiation-induced nerve damage, implying that FA might have some potential in the treatment of radiation-induced cognitive impairment.