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

Danqing Xin, Dexiang Liu, Lili Cao, Tingting Li, Weiwei Ma, Wengiang Chen, Xili Chu, Xin Zhou, Zhen Wang, Zhuoya Yu

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DOI: 10.1186/s12974-019-1488-2 DOI is the universal ID for this study.

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Background Hypoxia-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. Methods A 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. Results In 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. Conclusions These 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. Electronic supplementary material The online version of this article (10.1186/s12974-019-1488-2) contains supplementary material, which is available to authorized users.

Publish Year 2019
Country China
Rank Positive
Journal Journal of Neuroinflammation
Primary Topic Brain
Secondary TopicBrain Injury
Model Mouse
Tertiary TopicHypoxia-Ischemia
Vehicle Saline (Dissolved)
pH Neutral
Application Injection