PMID- 35695696
OWN - NLM
STAT- MEDLINE
DCOM- 20220908
LR  - 20221031
IS  - 1755-5949 (Electronic)
IS  - 1755-5930 (Print)
IS  - 1755-5930 (Linking)
VI  - 28
IP  - 10
DP  - 2022 Oct
TI  - Transplantation of Roxadustat-preconditioned bone marrow stromal cells improves 
      neurological function recovery through enhancing grafted cell survival in 
      ischemic stroke rats.
PG  - 1519-1531
LID - 10.1111/cns.13890 [doi]
AB  - 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-1alpha/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-1beta, IL-6, and TNF-alpha 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.
CI  - (c) 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & 
      Sons Ltd.
FAU - Chen, Jiayu
AU  - Chen J
AUID- ORCID: 0000-0003-3353-938X
AD  - Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, 
      Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical 
      University, Wenzhou, China.
FAU - Lin, Xiao
AU  - Lin X
AD  - Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, 
      Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical 
      University, Wenzhou, China.
FAU - Yao, Chaojie
AU  - Yao C
AD  - Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, 
      Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical 
      University, Wenzhou, China.
FAU - Bingwa, Lebohang Anesu
AU  - Bingwa LA
AD  - Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, 
      Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical 
      University, Wenzhou, China.
FAU - Wang, Hao
AU  - Wang H
AD  - Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, 
      Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical 
      University, Wenzhou, China.
FAU - Lin, Zhongxiao
AU  - Lin Z
AD  - Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, 
      Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical 
      University, Wenzhou, China.
FAU - Jin, Kunlin
AU  - Jin K
AD  - Department of Pharmacology and Neuroscience, University of North Texas Health 
      Science Center, Fort Worth, Texas, USA.
FAU - Zhuge, Qichuan
AU  - Zhuge Q
AD  - Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, 
      Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical 
      University, Wenzhou, China.
FAU - Yang, Su
AU  - Yang S
AD  - Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, 
      Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical 
      University, Wenzhou, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220613
PL  - England
TA  - CNS Neurosci Ther
JT  - CNS neuroscience & therapeutics
JID - 101473265
RN  - 0 (Isoquinolines)
RN  - TE7660XO1C (Glycine)
RN  - X3O30D9YMX (roxadustat)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/metabolism
MH  - Bone Marrow Transplantation
MH  - *Brain Ischemia/drug therapy/metabolism
MH  - Cell Survival
MH  - Glycine/analogs & derivatives
MH  - Infarction, Middle Cerebral Artery/metabolism/therapy
MH  - *Ischemic Stroke
MH  - Isoquinolines
MH  - *Mesenchymal Stem Cell Transplantation
MH  - *Mesenchymal Stem Cells/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Recovery of Function/physiology
MH  - *Stroke/drug therapy/metabolism
PMC - PMC9437235
OTO - NOTNLM
OT  - HIF-1alpha/BNIP3 signal pathway
OT  - autophagy
OT  - bone marrow stromal cells
OT  - stroke
COIS- The authors declare no conflict of interest.
EDAT- 2022/06/14 06:00
MHDA- 2022/09/09 06:00
PMCR- 2022/06/13
CRDT- 2022/06/13 09:43
PHST- 2022/05/25 00:00 [revised]
PHST- 2022/01/09 00:00 [received]
PHST- 2022/05/26 00:00 [accepted]
PHST- 2022/06/14 06:00 [pubmed]
PHST- 2022/09/09 06:00 [medline]
PHST- 2022/06/13 09:43 [entrez]
PHST- 2022/06/13 00:00 [pmc-release]
AID - CNS13890 [pii]
AID - 10.1111/cns.13890 [doi]
PST - ppublish
SO  - CNS Neurosci Ther. 2022 Oct;28(10):1519-1531. doi: 10.1111/cns.13890. Epub 2022 
      Jun 13.