神经炎症
缺氧(环境)
免疫系统
神经退行性变
缺血
发病机制
医学
脑病
缺氧缺血性脑病
免疫学
小胶质细胞
炎症
整合素αM
脑损伤
病理
疾病
内科学
化学
氧气
有机化学
作者
Kerstin Mülling,Alexa Josephine Fischer,Elena Siakaeva,Mathis Richter,Sharareh Bordbari,Ilona Spyra,Christian Köster,Dirk M. Hermann,Matthias Gunzer,Ursula Felderhoff‐Müser,Ivo Bendix,Jadwiga Jabłońska,Josephine Herz
标识
DOI:10.1016/j.bbi.2020.12.012
摘要
Neonatal encephalopathy following hypoxia–ischemia (HI) is a major cause of long-term morbidity and mortality in children. Even though HI-induced neuroinflammation, involving infiltration of peripheral immune cells into the CNS has been associated with disease pathogenesis, the specific role of neutrophils is highly debated. Due to immaturity of the neonatal immune system, it has been assumed that neutrophils are less clinically relevant in neonatal HI-induced brain injury. In the present study, we demonstrate that neutrophils are rapidly activated in the neonatal brain after exposure to experimental HI, revealed by an enhanced proportion of CD86+ cells and an increased expression of CD11b compared to splenic and blood neutrophils. Furthermore, production of reactive oxygen species and the proportion of hyperactivated/aged (CXCR4+CD62L−) cells was enhanced in brain compared to peripheral neutrophils. Delayed neutrophil depletion, initiated 12 h after HI resulted in reduced cellular neurodegeneration, associated with reduced micro- and astroglial activation. In the present study, we uncovered a new complex switch of the phenotype in brain neutrophils, which may offer new possibilities for the development of selective therapeutic approaches by modulation of neutrophils in the early post-hypoxic disease phase.
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