PMID- 34549680
OWN - NLM
STAT- MEDLINE
DCOM- 20220223
LR  - 20220428
IS  - 1532-2513 (Electronic)
IS  - 0892-3973 (Linking)
VI  - 43
IP  - 6
DP  - 2021 Dec
TI  - Effects of stem cell-derived exosomes on neuronal apoptosis and inflammatory 
      cytokines in rats with cerebral ischemia-reperfusion injury via PI3K/AKT 
      pathway-mediated mitochondrial apoptosis.
PG  - 731-740
LID - 10.1080/08923973.2021.1976794 [doi]
AB  - OBJECTIVE: This study aimed to investigate the effects of stem cell-derived 
      exosomes (SC-Exos) on learning, memory, and neuronal apoptosis in rats with 
      cerebral ischemia-reperfusion injury and to determine whether SC-Exos exert their 
      effects via phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) 
      pathway-mediated mitochondrial pathways of apoptosis. MATERIALS AND METHODS: 
      Eighty rats were randomly allocated to control, model, SC-Exos, and PI3K 
      inhibitor groups. A model of focal cerebral ischemia-reperfusion was established 
      using the improved Longa method. Expression of interleukin-1alpha (IL-1alpha), 
      interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) 
      were compared in the brains and serum of each group. The expressions of Bcl-2, 
      Bax, cleaved-caspase-3, cleaved-caspase-9, cytochrome C (CytC), PI3K, and 
      AKT-related genes and proteins were evaluated by real-time quantitative 
      polymerase chain reaction and western blotting. RESULTS: The SC-Exos-group 
      exhibited more novel entries, less latency for the novel arm, and fewer entries 
      into the starting arm and other arms than the model group (p<.05). Lower 
      expression of the inflammatory cytokines IL-1alpha, IL-2, and TNF-alpha and higher 
      expression of IFN-gamma were observed in the SC-Exos group than in the model group. 
      TdT-mediated dUTP nick end labeling (TUNEL) assay showed that lower neural cell 
      apoptosis rate and expression of Bax, cleaved-caspase-3, cleaved-caspase-9, CytC, 
      PI3K, and AKT mRNA and proteins and higher expression of Bcl-2 mRNA and protein 
      were observed in the SC-Exos group than in the model group (p<.05). CONCLUSIONS: 
      SC-Exos can significantly ameliorate brain injury caused by cerebral 
      ischemia-reperfusion. The mechanism may be a novel therapeutic target for 
      ischemia-reperfusion injury.
FAU - Zhang, Ying
AU  - Zhang Y
AUID- ORCID: 0000-0002-5939-0440
AD  - Department of Nuclear Medicine, The Second Affiliated Hospital of Zhejiang 
      University School of Medicine, Hangzhou, China.
FAU - Yu, Jun
AU  - Yu J
AD  - Department of Nuclear Medicine, The Second Affiliated Hospital of Zhejiang 
      University School of Medicine, Hangzhou, China.
FAU - Liu, Jing
AU  - Liu J
AD  - Department of Nuclear Medicine, The Second Affiliated Hospital of Zhejiang 
      University School of Medicine, Hangzhou, China.
FAU - Liu, Hongbiao
AU  - Liu H
AD  - Department of Nuclear Medicine, The Second Affiliated Hospital of Zhejiang 
      University School of Medicine, Hangzhou, China.
FAU - Li, Jing
AU  - Li J
AD  - Department of Nuclear Medicine, The Second Affiliated Hospital of Zhejiang 
      University School of Medicine, Hangzhou, China.
LA  - eng
PT  - Journal Article
DEP - 20210922
PL  - England
TA  - Immunopharmacol Immunotoxicol
JT  - Immunopharmacology and immunotoxicology
JID - 8800150
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Apoptosis/physiology
MH  - Brain Ischemia/*metabolism/therapy
MH  - Cells, Cultured
MH  - Cytokines/antagonists & inhibitors/*metabolism
MH  - Exosomes/*transplantation
MH  - Humans
MH  - Inflammation Mediators/antagonists & inhibitors/metabolism
MH  - Male
MH  - Mitochondria/metabolism
MH  - Neurons/metabolism
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt/antagonists & inhibitors/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reperfusion Injury/*metabolism/therapy
MH  - Stem Cell Transplantation/*methods
OTO - NOTNLM
OT  - Phosphatidylinositol-3-kinase/protein kinase B
OT  - inflammatory cytokine
OT  - neuronal apoptosis
OT  - novel therapeutic target
OT  - stem cell-derived exosome cerebral ischemia-reperfusion injury
EDAT- 2021/09/23 06:00
MHDA- 2022/02/24 06:00
CRDT- 2021/09/22 08:42
PHST- 2021/09/23 06:00 [pubmed]
PHST- 2022/02/24 06:00 [medline]
PHST- 2021/09/22 08:42 [entrez]
AID - 10.1080/08923973.2021.1976794 [doi]
PST - ppublish
SO  - Immunopharmacol Immunotoxicol. 2021 Dec;43(6):731-740. doi: 
      10.1080/08923973.2021.1976794. Epub 2021 Sep 22.