Hydrogen-rich saline promotes microglia M2 polarization and complement-mediated synapse loss to restore behavioral deficits following hypoxia-ischemic in neonatal mice via AMPK activation

Journal of Neuroinflammation

Dexiang Liu¹  Weiwei Ma²  Zhen Wang²  Xin Zhou²  Xili Chu²  Danqing Xin²  Tingting Li²  Zhuoya Yu³  Lili Cao³  Wenqiang Chen⁴ 

[1] 0000 0004 1761 1174, grid.27255.37, Department of Medical Psychology, Shandong University School of Basic Medical Sciences, 44 Wenhua Xi Road, 250012, Jinan, Shandong, People’s Republic of China;0000 0004 1761 1174, grid.27255.37, Department of Physiology, Shandong University School of Basic Medical Sciences, 44 Wenhua Xi Road, 250012, Jinan, Shandong, People’s Republic of China;0000 0004 1761 1174, grid.27255.37, Department of Physiology, Shandong University School of Basic Medical Sciences, 44 Wenhua Xi Road, 250012, Jinan, Shandong, People’s Republic of China;0000 0004 1761 1174, grid.27255.37, Department of Medical Psychology, Shandong University School of Basic Medical Sciences, 44 Wenhua Xi Road, 250012, Jinan, Shandong, People’s Republic of China;grid.452402.5, Shandong University Qilu Hospital, Jinan, Shandong, People’s Republic of China;

关键词: M2 polarization;    Complement;    Synapse loss;    Hydrogen-rich saline;    Hypoxia-ischemia;   

DOI  :  10.1186/s12974-019-1488-2

来源: publisher

【 摘 要 】

BackgroundHypoxia-ischemia (HI) during the perinatal period is one of the most common causes of acute mortality and chronic neurologic morbidity. Hydrogen-rich saline (HS) treatment in neonatal mice has been reported to alleviate brain injury following HI, but the mechanisms involved are not known.MethodsA modified version of the Rice-Vannucci method for the induction of neonatal HI brain injury was performed on postnatal day 7 mouse pups. Animals or BV2-cells received HS and an AMPK inhibitor at indicative time post-injury.ResultsIn the current study, we show that HS treatment attenuated the accumulation of CD11b+/CD45high cells, suppressed HI-induced neuro-inflammation, induced microglial anti-inflammatory M2 polarization, was associated with promoting AMPK activation, and inhibited nuclear factor-κB activation as demonstrated both in vivo and in vitro. In addition, HS treatment reversed HI-induced neurological disabilities, was associated with improving damaged synapses, and restored the expression levels of synaptophysin and postsynaptic density protein 95 following HI insult. Furthermore, HI insult which increased levels of complement component C1q, C3, and C3aR1 was observed. Importantly, C1q deposited in the infarct core and lesion boundary zone following HI injury, was found to co-localize within regions of synapse loss, whereas HS treatment reversed these effects of HI on synapse loss and complement component levels. Notably, the AMPK inhibitor reversed the beneficial effects of HS as described above.ConclusionsThese results demonstrate that HS restored behavioral deficits after HI in neonatal mice. These beneficial effects, in part, involve promoting microglia M2 polarization and complement-mediated synapse loss via AMPK activation.

【 授权许可】

CC BY