PMID- 32326841
OWN - NLM
STAT- MEDLINE
DCOM- 20210903
LR  - 20210903
IS  - 1557-8534 (Electronic)
IS  - 1547-3287 (Linking)
VI  - 29
IP  - 14
DP  - 2020 Jul
TI  - Evaluating In Vitro Neonatal Hypoxic-Ischemic Injury Using Neural Progenitors 
      Derived from Human Embryonic Stem Cells.
PG  - 929-951
LID - 10.1089/scd.2020.0018 [doi]
AB  - In hypoxic-ischemic encephalopathy, the neural progenitors (NPs) of the 
      developing brain fail to replenish the oligodendrocyte progenitor cells lost 
      during hypoxic-ischemic injury (HII). In this study, we aim to examine the 
      influence of HII on the vulnerability of human NPs derived from human embryonic 
      stem cells with regard to cell survival and oxidative stress, followed by 
      assessment of cellular deregulation through measuring glutathione levels, basal 
      calcium, glutamate release, and intracellular calcium ([Ca(2+)](i)) response 
      under KCl and ATP stimulation. NPs were further evaluated for their fundamental 
      potential of self-renewal and proliferation, neural and glial progenitor pool, 
      and migration. Oxygen-glucose deprivation (OGD) of 90 min was sublethal for NPs, 
      yet significantly increased reactive oxygen species generation and oxidative 
      stress susceptibility, and decreased glutathione levels, along with a rise in 
      glutamate release, basal [Ca(2+)](i), and KCl and ATP-induced [Ca(2+)](i). 
      Distinct increase in gene expression for K(+) leak channel (Twik-related 
      acid-sensitive K(+) channel 1 [TASK-1]) and purinergic receptor P2X7, and 
      decrease of voltage-gated K(v) channels K(v)1.5, K(v)4.2, and K(v)4.3 were 
      observed. TASK-1 increase was detected by FACS too. OGD-insulted NPs showed 
      reduced migration potential and decline in glial progenitor population. This 
      study thus demonstrates for the first time that brief exposure of OGD does not 
      reduce the NP population, its proliferation, and self-renewal, but can induce 
      significant alteration in oxidative stress susceptibility, glutamate release, 
      [Ca(2+)](i) response to physiological stimulus, migration, and glial progenitor 
      pool. We thus infer that treatment strategies need to target repair of NPs of the 
      developing brain that is affected during intrapartum asphyxia, leading to varying 
      neurologic complications such as seizure, mental retardation, and/or cerebral 
      palsy.
FAU - Sowmithra, Sowmithra
AU  - Sowmithra S
AD  - Department of Biophysics, National Institute of Mental Health and Neurosciences, 
      Institute of National Importance, Bengaluru, India.
FAU - Jain, Nishtha Kusum
AU  - Jain NK
AD  - Department of Biophysics, National Institute of Mental Health and Neurosciences, 
      Institute of National Importance, Bengaluru, India.
FAU - Datta, Indrani
AU  - Datta I
AD  - Department of Biophysics, National Institute of Mental Health and Neurosciences, 
      Institute of National Importance, Bengaluru, India.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200610
PL  - United States
TA  - Stem Cells Dev
JT  - Stem cells and development
JID - 101197107
RN  - 0 (Biomarkers)
RN  - 0 (Multidrug Resistance-Associated Proteins)
RN  - 0 (Reactive Oxygen Species)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 660YQ98I10 (Potassium Chloride)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - GAN16C9B8O (Glutathione)
RN  - IY9XDZ35W2 (Glucose)
RN  - S88TT14065 (Oxygen)
RN  - SY7Q814VUP (Calcium)
RN  - Y49M64GZ4Q (multidrug resistance-associated protein 1)
SB  - IM
MH  - Adenosine Triphosphate/pharmacology
MH  - Animals
MH  - Animals, Newborn
MH  - Biomarkers/metabolism
MH  - Calcium/metabolism
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/drug effects
MH  - Cell Self Renewal/drug effects
MH  - Cell Survival/drug effects
MH  - Glucose
MH  - Glutamic Acid/metabolism
MH  - Glutathione/metabolism
MH  - Human Embryonic Stem Cells/drug effects/*pathology
MH  - Humans
MH  - Hypoxia-Ischemia, Brain/*pathology
MH  - Multidrug Resistance-Associated Proteins/metabolism
MH  - Neural Stem Cells/drug effects/*pathology
MH  - Oxidative Stress/drug effects
MH  - Oxygen
MH  - Potassium Chloride/pharmacology
MH  - Reactive Oxygen Species/metabolism
OTO - NOTNLM
OT  - PSA-NCAM
OT  - glial progenitor population
OT  - intracellular calcium
OT  - migration potential
OT  - oxidative stress susceptibility
OT  - self-renewal and proliferation
EDAT- 2020/04/25 06:00
MHDA- 2021/09/04 06:00
CRDT- 2020/04/25 06:00
PHST- 2020/04/25 06:00 [pubmed]
PHST- 2021/09/04 06:00 [medline]
PHST- 2020/04/25 06:00 [entrez]
AID - 10.1089/scd.2020.0018 [doi]
PST - ppublish
SO  - Stem Cells Dev. 2020 Jul;29(14):929-951. doi: 10.1089/scd.2020.0018. Epub 2020 
      Jun 10.