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Differential susceptibility of human neural progenitors and neurons to ischaemic injury

Citation

Liu, Y and Michalska, AE and Dottori, M and Eaton, ED and Courtney, J-M and Antonic, A and Howells, DW, Differential susceptibility of human neural progenitors and neurons to ischaemic injury, Brain Research Bulletin, 156 pp. 25-32. ISSN 0361-9230 (2020) [Refereed Article]


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DOI: doi:10.1016/j.brainresbull.2019.12.005

Abstract

Background: Neuroprotection for stroke has shown great promise but has had little translational success. Developing drugs for humans logically requires human tissue evaluation. Human embryonic stem cell (hESC)-derived neuronal cultures at different developmental stages were subject to oxygen glucose deprivation (OGD) to determine how developing maturity altered response to ischemic injury.

Methods: H9 hESCs were induced by Noggin to generate neural progenitors (NPs) and highly arbourised structurally complex neurons. They were both subjected to OGD or OGD with reoxygenation (OGD-R) for 1-6 h.Outcome was assessed by measures of cell death, survival and morphology.

Results: NPs did not die after OGD but experienced progressive loss of metabolic activity. Highly arbourised neurons showed minimal cell death initially but 44 % and 78 % died after 4 and 6 h OGD. Metabolic dysfunction was greater in these more mature neurons (∼70 %) than in NPs and evident after 1 h OGD, before detection of neuronal death at 4 h. OGD-R salvaged metabolic activity but not cell death in mature neurons. In NPs there was little metabolic salvage and cell death was induced (50 % and 65 % at 4 and 6 h OGD-R, respectively).

Conclusions: Highly arbourised neurons are more sensitive to ischaemic injury than NPs which did however develop marked vulnerability to prolonged injury with reoxygenation. These observations imply that therapeutic potential may be highly dependent of the developmental state of the neurons we aim to protect.

Item Details

Item Type:Refereed Article
Keywords:OGD sensitivity, stem cells, hESC neuronal differentiation
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Neurology and neuromuscular diseases
Objective Division:Health
Objective Group:Clinical health
Objective Field:Treatment of human diseases and conditions
UTAS Author:Eaton, ED (Dr Emma Eaton)
UTAS Author:Courtney, J-M (Dr Jo-Maree Courtney)
UTAS Author:Howells, DW (Professor David Howells)
ID Code:151759
Year Published:2020
Deposited By:Medicine
Deposited On:2022-08-04
Last Modified:2022-08-04
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