Erythropoietin ameliorates early brain injury after subarachnoid haemorrhage by modulating microglia polarization via the EPOR/JAK2-STAT3 pathway

Experimental Cell Research
Shanwu WeiBin Yi

Abstract

Inflammatory modulation mediated by microglial M1/M2 polarization is one of the main pathophysiological processes involved in early brain injury (EBI) after subarachnoid haemorrhage (SAH). Previous studies have shown that recombinant human erythropoietin (rhEPO) alleviates EBI following experimental SAH. However, the mechanisms of this beneficial effect are still poorly understood. Recent research has suggested that EPO shows anti-inflammatory properties. Therefore, we tried to analyse whether rhEPO administration influenced microglial M1/M2 polarization in early brain injury after SAH and to identify the underlying molecular mechanism of any such effect. We found that treatment with rhEPO markedly ameliorated SAH-induced EBI, as shown by reductions in brain cell apoptosis, neuronal necrosis, albumin exudation and brain edema. Moreover, the expression levels of p-JAK2 and p-STAT3 were significantly increased in the cortex after SAH induction and were further increased by EPO treatment; in addition, the p-JAK2 inhibitor AZD1480 impaired the protective effect of EPO against SAH-induced EBI in vivo. Furthermore, EPO promoted the polarization of microglia towards the protective M2 phenotype and alleviated inflammation. In cultured ...Continue Reading

Citations

Feb 8, 2018·Brain Sciences·Hirofumi Nishikawa, Hidenori Suzuki
Jan 8, 2020·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·A P Coulibaly, J J Provencio
Dec 7, 2019·Cellular and Molecular Neurobiology·Kevin Min Wei KheySherif Hanafy Mahmoud
Sep 23, 2020·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Deeya GaindhWei Lu
Oct 13, 2020·Frontiers in Cell and Developmental Biology·Carmen Hierro-BujalanceMonica Garcia-Alloza
Nov 19, 2020·International Journal of Molecular Sciences·Cecilia Zavala-TecuapetlaHiram Luna-Munguia
Apr 4, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zhongnan YangFengmin Shao
Jun 8, 2021·Neural Plasticity·Xin HuangLiang Wen
Jul 3, 2021·International Journal of Molecular Sciences·Teodora Larisa TimisIoan Stefan Florian
Oct 15, 2021·Stroke and Vascular Neurology·Zhiyuan Vera ZhengGeorge K C Wong

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