百日咳トキシンは虚血性脳卒中に伴う微小グリア活性化を改善する

Pertussis Toxin Ameliorates Microglial Activation Associated With Ischemic Stroke.

• Feihui Zhou
• Rong Liu
• Pengcheng Han
• Xingkui Zhang
• Zhigao Li
• Shen Zhang
• Chang Liu
• Yang Xia
• Zhiwei Tang

抄録

:中大脳動脈閉塞性脳卒中モデルを用いて、PTX 400 ng/日投与による神経機能、梗塞サイズ、ミクログリア分布、活性化の評価を行い、その効果を検証した。並行して、初代培養ミクログリアに対するPTXの効果を、ミクログリア増殖、活性化、サイトカイン放出、CX3CR1発現を評価することにより検討した。さらに、PTXはリポ多糖刺激性のミクログリア増殖、インターロイキン1β（IL-1β）および腫瘍壊死因子α（TNF-α）の遊離、CX3CR1の発現を有意に減少させた。PTX治療の効果は、IL-1βやTNF-αなどの炎症性サイトカインの産生が減少し、ケモカインCX3CR1の発現が減少したことに起因していると考えられる。

: To investigate the effect and the underlying mechanism of Pertussis toxin (PTX) on microglia in the setting of cerebral ischemia. : We tested the effect of PTX 400 ng/days on middle cerebral artery occlusion stroke model by evaluating the neurologic function, infarct size, microglial distribution, and activation. In parallel, we also tested the effect of PTX on primary cultured microglia by evaluating microglial proliferation, activation, cytokine release, and CX3CR1 expression. : PTX reduced the poststroke infarct size, improved the neurologic function as evaluated by Longa score, and reduced microglial aggregation and activation in the infarcted area. Further, PTX significantly decreased lipopolysaccharide-stimulated microglial proliferation, the release of interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α), and the expression of CX3CR1. : PTX treatment in stroke reduced microglial accumulation and activation in the infarct zone, resulting in a better functional outcome. The benefits of PTX treatment may be attributed to the reduced production of proinflammatory cytokine such as IL-1β and TNF-α and reduced expression of chemokine CX3CR1.

Copyright © 2020 Zhou, Liu, Han, Zhang, Li, Zhang, Liu, Xia and Tang.