Open AccessTransplantation of Roxadustat‐preconditioned bone marrow stromal cells improves neurological function recovery through enhancing grafted cell survival in ischemic stroke rats
Author(s) -
Chen Jiayu,
Lin Xiao,
Yao Chaojie,
Bingwa Lebohang Anesu,
Wang Hao,
Lin Zhongxiao,
Jin Kunlin,
Zhuge Qichuan,
Yang Su
Publication year - 2022
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.13890
Subject(s) - medicine , neun , transplantation , apoptosis , stromal cell , stroke (engine) , bone marrow , pharmacology , pathology , chemistry , immunohistochemistry , mechanical engineering , biochemistry , engineering
Abstract Aims The therapeutic effect of bone marrow stromal cell (BMSC) transplantation for ischemic stroke is limited by its low survival rate. The purpose of this study was to evaluate whether Roxadustat (FG‐4592) pretreatment could promote the survival rate of grafted BMSCs and improve neurological function deficits in ischemia rats. Methods Oxygen–glucose deprivation (OGD) and permanent middle cerebral artery occlusion (pMCAO) were constructed as stroke models in vitro and in vivo. Flow cytometry analysis and expression of Bax and Bcl‐2 were detected to evaluate BMSCs apoptosis. Infarct volume and neurobehavioral score were applied to evaluate functional recovery. Inflammatory cytokine expression, neuronal apoptosis, and microglial M1 polarization were assessed to confirm the enhanced neurological recovery after FG‐4592 pretreatment. Results FG‐4592 promoted autophagy level to inhibit OGD‐induced apoptosis through HIF‐1α/BNIP3 pathway. GFP and Ki67 double staining showed an improved survival rate of BMSCs in the FG‐4592 group, whereas infarct volume and neurobehavioral score verified its enhanced neurological recovery activity simultaneously. NeuN and Iba‐1 fluorescence staining showed improved neural survival and decreased microglial activation, along with decreased IL‐1β, IL‐6, and TNF‐α levels through the TLR‐4/NF‐kB pathway. Conclusions FG‐4592 pretreated BMSCs improve neurological function recovery after stroke and are likely to be a promising strategy for stroke management.