Immunopharmacology and immunotoxicology · 2025
Edaravone dexborneol attenuates neuroinflammation in acute cerebral ischemia-reperfusion injury through the CXCL13/CXCR5/NF-κB pathway.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Men Donghai, Huang Zixiong, Lin Heng, Wu Weichuan, Yin Yanqing
Аннотация
BACKGROUND: Edaravone dexborneol is an agent used to treat patients with acute ischemic stroke (AIS); however, the underlying mechanisms of this drug remain unclear.
OBJECTIVE: To investigate whether Edaravone dexborneol protect against cerebral ischemia-reperfusion injury (CIRI), a common feature of AIS, by modulating neuroinflammation through the regulation of the CXC motif ligand 13 (CXCL13)/CXC chemokine receptor type 5 (CXCR5)/nuclear factor-κB (NF-κB) signaling pathway.
MATERIALS AND METHODS: Primary microglia were subjected to hypoxia-glucose deprivation and reoxygenation (OGD/R) treatment. A middle cerebral artery occlusion (MCAO) rat model was constructed. Various tests, such as cell counting kit-8 (CCK-8) assay, western blot, 2, 3, 5-triphenyl tetrazolium chloride staining, and neurobehavioral tests, were conducted.
RESULTS: Our in vitro experiments showed Edaravone dexborneol alleviated OGD/R-induced microglia injury, modulated microglial M1/M2 polarization, and regulated the secretion of inflammatory cytokines. Subsequently, our in vivo experiments revealed Edaravone dexborneol exhibited superior efficacy compared to Edaravone in ameliorating the short-term and long-term neurological deficits, reducing brain infarction volume and brain water content, and decreasing the expression of CXCL13 and CXCR5 in MCAO rats. Furthermore, the expressions of CXCL13, CXCR5, p-NF-κB, IL-1β, and TNF-α were upregulated following MCAO but downregulated after treatment with Edaravone dexborneol, which was reversed by exogenous administration of rh-CXCL13.
CONCLUSION: Our results validate the protective efficacy of Edaravone dexborneol in OGD/R-induced microglia and MCAO rats. This effect may be attributed to its ability to mitigate neuroinflammation by modulating microglial M1/M2 polarization in vitro and inhibiting the CXCL13/CXCR5 axis and its associated NF-κB signaling pathway in vivo.
OBJECTIVE: To investigate whether Edaravone dexborneol protect against cerebral ischemia-reperfusion injury (CIRI), a common feature of AIS, by modulating neuroinflammation through the regulation of the CXC motif ligand 13 (CXCL13)/CXC chemokine receptor type 5 (CXCR5)/nuclear factor-κB (NF-κB) signaling pathway.
MATERIALS AND METHODS: Primary microglia were subjected to hypoxia-glucose deprivation and reoxygenation (OGD/R) treatment. A middle cerebral artery occlusion (MCAO) rat model was constructed. Various tests, such as cell counting kit-8 (CCK-8) assay, western blot, 2, 3, 5-triphenyl tetrazolium chloride staining, and neurobehavioral tests, were conducted.
RESULTS: Our in vitro experiments showed Edaravone dexborneol alleviated OGD/R-induced microglia injury, modulated microglial M1/M2 polarization, and regulated the secretion of inflammatory cytokines. Subsequently, our in vivo experiments revealed Edaravone dexborneol exhibited superior efficacy compared to Edaravone in ameliorating the short-term and long-term neurological deficits, reducing brain infarction volume and brain water content, and decreasing the expression of CXCL13 and CXCR5 in MCAO rats. Furthermore, the expressions of CXCL13, CXCR5, p-NF-κB, IL-1β, and TNF-α were upregulated following MCAO but downregulated after treatment with Edaravone dexborneol, which was reversed by exogenous administration of rh-CXCL13.
CONCLUSION: Our results validate the protective efficacy of Edaravone dexborneol in OGD/R-induced microglia and MCAO rats. This effect may be attributed to its ability to mitigate neuroinflammation by modulating microglial M1/M2 polarization in vitro and inhibiting the CXCL13/CXCR5 axis and its associated NF-κB signaling pathway in vivo.