Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Regulation Microglia Activation Mediated Neuroinflammation to Ameliorate Ischemia-reperfusion Injury via STAT5-NF-κB Pathway in Ischemic Stroke

Version 1 : Received: 4 August 2022 / Approved: 8 August 2022 / Online: 8 August 2022 (13:18:00 CEST)

A peer-reviewed article of this Preprint also exists.

Pu, Z.; Xia, S.; Shao, P.; Bao, X.; Wu, D.; Xu, Y. Regulation of Microglia-Activation-Mediated Neuroinflammation to Ameliorate Ischemia-Reperfusion Injury Via the STAT5-NF-κB Pathway in Ischemic Stroke. Brain Sci. 2022, 12, 1153. Pu, Z.; Xia, S.; Shao, P.; Bao, X.; Wu, D.; Xu, Y. Regulation of Microglia-Activation-Mediated Neuroinflammation to Ameliorate Ischemia-Reperfusion Injury Via the STAT5-NF-κB Pathway in Ischemic Stroke. Brain Sci. 2022, 12, 1153.

Abstract

Inflammatory reaction after ischemia-reperfusion contributes significantly to prognosis, and microglia activation is the main resource of inflammation in nervous system. STAT5 is proving to be a highly effective anti-inflammatory therapy with great potential, and inhibition of STAT5 has demonstrated significant anti-inflammation and therapeutic effects, but rarely focus on mechanism of neuroinflammation and brain injury from ischemia-reperfusion. It is the first time to found that the anti-inflammation of dauricine is mainly through STAT5-NF-κB pathway, might act as a STAT5 inhibitor. Dauricine suppressed the inflammation cytokines Eotaxin, KC, TNF-α, IL-1α, IL-1β, IL-6, IL-12β, IL-17α, and also inhibited the microglia activation. STAT5b mutant at Tyr-699 reversed the protective effect of dauricine on oxygen-glucose deprivation-reperfusion injury of neurons, and reactivated the suppression of dauricine on P-NF-κB of microglia. These results suggest that dauricine might suppress the neuroinflammation and protect the neuron from the injury of post-ischemia-reperfusion via mediating the microglia activation through STAT5-NF-κB pathway, and ss a potential therapeutic target for neuroinflammation, STAT5 needs to be raised concern in ischemic stroke.

Keywords

dauricine; STAT5; NF-κB; Inflammation; Ischemia-reperfusion injury

Subject

Medicine and Pharmacology, Neuroscience and Neurology

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