The role of the ATP-adenosine axis in ischemic stroke.

IF 7.9 2区 医学 Q1 IMMUNOLOGY Seminars in Immunopathology Pub Date : 2023-05-01 DOI:10.1007/s00281-023-00987-3
Ines Sophie Schädlich, Riekje Winzer, Joschi Stabernack, Eva Tolosa, Tim Magnus, Björn Rissiek
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引用次数: 5

Abstract

In ischemic stroke, the primary neuronal injury caused by the disruption of energy supply is further exacerbated by secondary sterile inflammation. The inflammatory cascade is largely initiated by the purine adenosine triphosphate (ATP) which is extensively released to the interstitial space during brain ischemia and functions as an extracellular danger signaling molecule. By engaging P2 receptors, extracellular ATP activates microglia leading to cytokine and chemokine production and subsequent immune cell recruitment from the periphery which further amplifies post-stroke inflammation. The ectonucleotidases CD39 and CD73 shape and balance the inflammatory environment by stepwise degrading extracellular ATP to adenosine which itself has neuroprotective and anti-inflammatory signaling properties. The neuroprotective effects of adenosine are mainly mediated through A1 receptors and inhibition of glutamatergic excitotoxicity, while the anti-inflammatory capacities of adenosine have been primarily attributed to A2A receptor activation on infiltrating immune cells in the subacute phase after stroke. In this review, we summarize the current state of knowledge on the ATP-adenosine axis in ischemic stroke, discuss contradictory results, and point out potential pitfalls towards translating therapeutic approaches from rodent stroke models to human patients.

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atp -腺苷轴在缺血性卒中中的作用。
在缺血性卒中中,能量供应中断引起的原发性神经元损伤会因继发性无菌炎症而进一步加剧。炎症级联反应主要由嘌呤三磷酸腺苷(ATP)引发,ATP在脑缺血时广泛释放到脑间质,是一种细胞外危险信号分子。通过参与P2受体,细胞外ATP激活小胶质细胞,导致细胞因子和趋化因子的产生,随后从外周募集免疫细胞,进一步放大脑卒中后炎症。外核苷酶CD39和CD73通过逐步将细胞外ATP降解为腺苷来形成和平衡炎症环境,腺苷本身具有神经保护和抗炎信号特性。腺苷的神经保护作用主要通过A1受体和抑制谷氨酸能兴奋性毒性介导,而腺苷的抗炎能力主要归因于A2A受体在脑卒中亚急性期对浸润性免疫细胞的激活。在这篇综述中,我们总结了缺血性卒中中atp -腺苷轴的知识现状,讨论了相互矛盾的结果,并指出了将啮齿动物卒中模型的治疗方法转化为人类患者的潜在缺陷。
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来源期刊
Seminars in Immunopathology
Seminars in Immunopathology 医学-病理学
CiteScore
19.80
自引率
2.20%
发文量
69
审稿时长
12 months
期刊介绍: The aim of Seminars in Immunopathology is to bring clinicians and pathologists up-to-date on developments in the field of immunopathology.For this purpose topical issues will be organized usually with the help of a guest editor.Recent developments are summarized in review articles by authors who have personally contributed to the specific topic.
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