Lack of Neuroprotection with a Single Intravenous Infusion of Human Amnion Epithelial Cells after Severe Hypoxia-Ischemia in Near-Term Fetal Sheep.
fetal sheep
human amnion epithelial cells
hypoxia ischemia
inflammation
neuroprotection
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
29 Jul 2022
29 Jul 2022
Historique:
received:
05
07
2022
revised:
27
07
2022
accepted:
27
07
2022
entrez:
12
8
2022
pubmed:
13
8
2022
medline:
16
8
2022
Statut:
epublish
Résumé
Hypoxic-ischemic encephalopathy (HIE) around the time of birth results from loss of oxygen (hypoxia) and blood supply (ischemia). Exogenous infusion of multi-potential cells, including human amnion epithelial cells (hAECs), can reduce hypoxic-ischemic (HI) brain injury. However, there are few data on treatment of severe HI in large animal paradigms at term. The aim of the current study was to determine whether infusion of hAECs early after injury may reduce brain damage after ischemia in near-term fetal sheep. Chronically instrumented fetal sheep (0.85 gestation) received 30 min of global cerebral ischemia followed by intravenous infusion of hAECs from 2 h after the end of ischemia (ischemia-hAEC, n = 6) or saline (ischemia-vehicle, n = 7). Sham control animals received sham ischemia with vehicle infusion (sham control, n = 8). Ischemia was associated with significant suppression of EEG power and spectral edge frequency until the end of the experiment and a secondary rise in cortical impedance from 24 to 72 h, which were not attenuated by hAEC administration. Ischemia was associated with loss of neurons in the cortex, thalamus, striatum and hippocampus, loss of white matter oligodendrocytes and increased microglial numbers in the white matter, which were not affected by hAEC infusion. A single intravenous administration of hAECs did not reduce electrographic or histological brain damage after 30 min of global cerebral ischemia in near-term fetal sheep.
Sections du résumé
BACKGROUND
BACKGROUND
Hypoxic-ischemic encephalopathy (HIE) around the time of birth results from loss of oxygen (hypoxia) and blood supply (ischemia). Exogenous infusion of multi-potential cells, including human amnion epithelial cells (hAECs), can reduce hypoxic-ischemic (HI) brain injury. However, there are few data on treatment of severe HI in large animal paradigms at term. The aim of the current study was to determine whether infusion of hAECs early after injury may reduce brain damage after ischemia in near-term fetal sheep.
METHODS
METHODS
Chronically instrumented fetal sheep (0.85 gestation) received 30 min of global cerebral ischemia followed by intravenous infusion of hAECs from 2 h after the end of ischemia (ischemia-hAEC, n = 6) or saline (ischemia-vehicle, n = 7). Sham control animals received sham ischemia with vehicle infusion (sham control, n = 8).
RESULTS
RESULTS
Ischemia was associated with significant suppression of EEG power and spectral edge frequency until the end of the experiment and a secondary rise in cortical impedance from 24 to 72 h, which were not attenuated by hAEC administration. Ischemia was associated with loss of neurons in the cortex, thalamus, striatum and hippocampus, loss of white matter oligodendrocytes and increased microglial numbers in the white matter, which were not affected by hAEC infusion.
CONCLUSIONS
CONCLUSIONS
A single intravenous administration of hAECs did not reduce electrographic or histological brain damage after 30 min of global cerebral ischemia in near-term fetal sheep.
Identifiants
pubmed: 35955531
pii: ijms23158393
doi: 10.3390/ijms23158393
pmc: PMC9369428
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Health Research Council of New Zealand
ID : 17/601
Organisme : Health Research Council of New Zealand
ID : 12/613
Organisme : Health Research Council of New Zealand
ID : 16/003
Organisme : NHMRC
ID : APP1136216 (PI Suzanne Miller)
Organisme : NHMRC
ID : APP1159277 (PI : Rebecca Lim)
Références
Reprod Fertil Dev. 1996;8(1):157-62
pubmed: 8713735
Curr Protoc Stem Cell Biol. 2010 Apr;Chapter 1:Unit 1E.6
pubmed: 20373516
Front Physiol. 2020 Feb 21;11:119
pubmed: 32153424
Cell Transplant. 2019 Dec;28(12):1552-1559
pubmed: 31512502
Stem Cell Res Ther. 2011 May 19;2(3):25
pubmed: 21596003
Cell Transplant. 2017 Apr 13;26(4):541-553
pubmed: 27938480
Best Pract Res Clin Obstet Gynaecol. 2016 Feb;31:13-29
pubmed: 26547389
Cell Stem Cell. 2013 Oct 3;13(4):392-402
pubmed: 24094322
Stroke. 2010 Sep;41(9):2064-70
pubmed: 20616329
J Perinatol. 2021 Sep;41(9):2134-2140
pubmed: 34175900
Front Neurol. 2014 Oct 09;5:200
pubmed: 25346720
Am J Obstet Gynecol. 2008 Dec;199(6):587-95
pubmed: 19084096
Neurology. 2014 Apr 8;82(14):1277-86
pubmed: 24610327
PLoS One. 2013;8(1):e51253
pubmed: 23300948
J Cereb Blood Flow Metab. 2019 Feb;39(2):223-239
pubmed: 28895475
Dev Neurosci. 2013;35(2-3):272-82
pubmed: 23571644
Differentiation. 2011 Mar;81(3):162-71
pubmed: 21339039
Ann Neurol. 2012 May;71(5):589-600
pubmed: 22522476
Pediatr Res. 1994 Mar;35(3):329-33
pubmed: 8190521
Neuropathol Appl Neurobiol. 1979 Mar-Apr;5(2):103-14
pubmed: 471183
Clin Perinatol. 2014 Mar;41(1):133-48
pubmed: 24524451
J Comp Neurol. 1969 Mar;135(3):249-62
pubmed: 4306038
Lancet Neurol. 2022 Jun;21(6):528-536
pubmed: 35568047
PLoS One. 2014 May 27;9(5):e96558
pubmed: 24865217
Lancet Glob Health. 2021 Sep;9(9):e1273-e1285
pubmed: 34358491
Stem Cell Res Ther. 2017 Feb 28;8(1):46
pubmed: 28241859
Ann Neurol. 1992 Jan;31(1):14-21
pubmed: 1543346
N Engl J Med. 2014 Jul 10;371(2):140-9
pubmed: 25006720
Obstet Gynecol Int. 2014;2014:314159
pubmed: 24693290
Childs Nerv Syst. 2014 Jan;30(1):37-46
pubmed: 24178233
Brain Res. 2020 Nov 1;1746:147001
pubmed: 32585139
PLoS One. 2014 May 05;9(5):e96530
pubmed: 24797081
Cytotherapy. 2013 Aug;15(8):1021-9
pubmed: 23643416
Cytotherapy. 2021 Jun;23(6):521-535
pubmed: 33262073
Stem Cells Transl Med. 2021 Mar;10(3):427-440
pubmed: 33103374
Pediatrics. 1993 Jan;91(1):128-34
pubmed: 8416475
Front Neurosci. 2013 Oct 24;7:194
pubmed: 24167471
Pediatr Res. 2013 Dec;74 Suppl 1:50-72
pubmed: 24366463