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Microglia-Astrocyte Cross Talk through IL-18/IL-18R Signaling Modulates Migraine-like Behavior in Experimental Models of Migraine
Neuroscience ( IF 3.3 ) Pub Date : 2020-10-31 , DOI: 10.1016/j.neuroscience.2020.10.019
Qiaoyu Gong 1 , Yao Lin 1 , Zuneng Lu 1 , Zheman Xiao 1
Affiliation  

Interleukin-18 (IL-18) is an important regulator of innate and immune responses, and is involved in the pain process, including neuropathic and cancer pain. The current study demonstrated that inflammatory soup (IS) dural infusions elicited the activation of microglia and astrocytes. In comparison, IS dural infusions induced the upregulation of IL-18 and IL-18R in microglia and astrocytes, respectively. Blocking the IL-18 signaling pathway attenuated nociceptive behavior. In comparison, blocking IL-18 signaling also suppressed the activation of astrocytes and nuclear factor-kappa B (NF-κB). IL-18 dural infusions induced nociceptive behavior and glia activation. IL-18 is a product of the activation of microglial toll-like receptor 4 (TLR4), and it acted on IL-18R expressed in astrocytes. Subsequently, it stimulated the activation of nuclear factor-kappa B (NF-κB), leading to the activation of astrocytes. In conclusion, IL-18-mediated microglia/astrocyte interactions in the medullary dorsal horn likely contribute to the development of hyperpathia or allodynia induced by migraines.



中文翻译:

通过 IL-18/IL-18R 信号传导的小胶质细胞-星形胶质细胞串扰调节偏头痛实验模型中的偏头痛样行为

白细胞介素 18 (IL-18) 是先天和免疫反应的重要调节剂,并参与疼痛过程,包括神经性疼痛和癌症疼痛。目前的研究表明,炎症汤 (IS) 硬脑膜输注引发了小胶质细胞和星形胶质细胞的激活。相比之下,IS 硬脑膜输注分别诱导小胶质细胞和星形胶质细胞中 IL-18 和 IL-18R 的上调。阻断 IL-18 信号通路减弱了伤害感受行为。相比之下,阻断 IL-18 信号传导也抑制了星形胶质细胞和核因子-κB (NF-κB) 的激活。IL-18 硬脑膜输注诱导伤害行为和神经胶质细胞活化。IL-18 是小胶质细胞 toll 样受体 4 (TLR4) 激活的产物,它作用于星形胶质细胞中表达的 IL-18R。随后,它刺激了核因子-κB (NF-κB) 的激活,从而导致星形胶质细胞的激活。总之,IL-18 介导的髓质背角中的小胶质细胞/星形胶质细胞相互作用可能导致偏头痛引起的过度疼痛或异常性疼痛的发展。

更新日期:2020-11-13
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