PMID- 35164474
OWN - NLM
STAT- MEDLINE
DCOM- 20220322
LR  - 20220322
IS  - 0219-6352 (Print)
IS  - 0219-6352 (Linking)
VI  - 21
IP  - 1
DP  - 2022 Jan 28
TI  - Therapeutic effects of human umbilical cord mesenchymal stem cell on 
      sepsis-associated encephalopathy in mice by regulating PI3K/AKT pathway.
PG  - 38
LID - 10.31083/j.jin2101038 [doi]
AB  - Sepsis-associated encephalopathy is a common brain diseases, presenting severe 
      diffuse brain dysfunction. The umbilical cord mesenchymal stem cells have been 
      reported to have protective role for treating diseases, while its role in 
      sepsis-associated encephalopathy remained elusive. This brief report investigated 
      the therapeutic effect of umbilical cord mesenchymal stem cells on 
      sepsis-associated encephalopathy in mice model and uncovering the underlying 
      mechanism. The sepsis-associated encephalopathy mice were injected with 3 mg/kg 
      lipopolysaccharide. An enzyme-linked immunosorbent assay was carried out to 
      determine the production of inflammatory cytokines. Morris water maze test was 
      used to evaluate mice's neurological dysfunction. Cell apoptosis and tissue 
      injury of the cerebral cortex were assessed using terminal deoxynucleotidyl 
      transferase-mediated dUTP nick end labeling (TUNEL) assay and HE staining. Evans 
      Blue leakage detection was used to examine the blood-brain barrier integrity. The 
      protein levels were determined using Western blot. Results showed that the 
      productions of inflammatory cytokines including interleukin 6 (IL-6), 
      interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), and high mobility group 
      box protein 1 (HMGB1) and activated NF-kappaB were increased in sepsis-associated 
      encephalopathy mice, which were decreased by umbilical cord mesenchymal stem 
      cells treatment. Besides, umbilical cord mesenchymal stem cells inhibited 
      lipopolysaccharide-induced cell apoptosis and neuron injury of the cerebral 
      cortex in sepsis-associated encephalopathy mice. Moreover, cognitive dysfunction 
      was observed in sepsis-associated encephalopathy mice, which was alleviated by 
      umbilical cord mesenchymal stem cells. Furthermore, umbilical cord mesenchymal 
      stem cells activated PI3K/AKT signaling pathway. In conclusion, umbilical cord 
      mesenchymal stem cells alleviated inflammation, cell apoptosis and neuron injury 
      of the cerebral cortex, and cognitive dysfunction in sepsis-associated 
      encephalopathy animal model in a PI3K/AKT dependent pathway, making them to be a 
      promising therapeutic strategy for treating sepsis-associated encephalopathy.
CI  - (c) 2022 The Author(s). Published by IMR Press.
FAU - Zhang, Zhe
AU  - Zhang Z
AD  - Department of Emergency Medicine, The First People's Hospital of Yuhang District 
      Hangzhou, 311100 Hangzhou, Zhejiang, China.
FAU - Wang, Li
AU  - Wang L
AD  - Department of Emergency Medicine, The Second Affiliated Hospital Zhejiang 
      University School of Medicine, 310002 Hangzhou, Zhejiang, China.
FAU - Li, Feng
AU  - Li F
AD  - Department of Emergency Medicine, The First People's Hospital of Yuhang District 
      Hangzhou, 311100 Hangzhou, Zhejiang, China.
FAU - Qian, Xiangfeng
AU  - Qian X
AD  - Department of Emergency Medicine, The First People's Hospital of Yuhang District 
      Hangzhou, 311100 Hangzhou, Zhejiang, China.
FAU - Hong, Zhixing
AU  - Hong Z
AD  - Department of Emergency Medicine, The First People's Hospital of Yuhang District 
      Hangzhou, 311100 Hangzhou, Zhejiang, China.
FAU - Wu, Longchuan
AU  - Wu L
AD  - Department of Emergency Medicine, The First People's Hospital of Yuhang District 
      Hangzhou, 311100 Hangzhou, Zhejiang, China.
FAU - Jiang, Yinsheng
AU  - Jiang Y
AD  - Department of Emergency Medicine, The First People's Hospital of Yuhang District 
      Hangzhou, 311100 Hangzhou, Zhejiang, China.
FAU - Hu, Haiqiang
AU  - Hu H
AD  - Department of Cardiovascular Medicine, The First People's Hospital of Yuhang 
      District Hangzhou, 311100 Hangzhou, Zhejiang, China.
AD  - Department of Cardiovascular Medicine, The Second Clinical Medical College of 
      Zhejiang Chinese Medicine University, 310053 Hangzhou, Zhejiang, China.
LA  - eng
PT  - Journal Article
PL  - Singapore
TA  - J Integr Neurosci
JT  - Journal of integrative neuroscience
JID - 101156357
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/physiology
MH  - *Cerebral Cortex/immunology/pathology
MH  - Cognitive Dysfunction/etiology/*therapy
MH  - Disease Models, Animal
MH  - Humans
MH  - Male
MH  - *Mesenchymal Stem Cell Transplantation
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Phosphatidylinositol 3-Kinase/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Sepsis-Associated Encephalopathy/complications/*immunology/*therapy
MH  - Signal Transduction/physiology
MH  - *Umbilical Cord
OTO - NOTNLM
OT  - Cerebral cortex
OT  - Cognitive dysfunction
OT  - PI3K/AKT pathway
OT  - Sepsis-associated encephalopathy
OT  - Umbilical cord mesenchymal stem cells
COIS- The authors declare no conflict of interest.
EDAT- 2022/02/16 06:00
MHDA- 2022/03/23 06:00
CRDT- 2022/02/15 03:23
PHST- 2021/06/03 00:00 [received]
PHST- 2021/08/05 00:00 [revised]
PHST- 2021/09/15 00:00 [accepted]
PHST- 2022/02/15 03:23 [entrez]
PHST- 2022/02/16 06:00 [pubmed]
PHST- 2022/03/23 06:00 [medline]
AID - S0219-6352(22)00298-4 [pii]
AID - 10.31083/j.jin2101038 [doi]
PST - ppublish
SO  - J Integr Neurosci. 2022 Jan 28;21(1):38. doi: 10.31083/j.jin2101038.