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Differential susceptibility of human neural progenitors and neurons to ischaemic injury

journal contribution
posted on 2023-05-21, 10:42 authored by Liu, Y, Michalska, AE, Dottori, M, Eaton, ED, Jo-Maree CourtneyJo-Maree Courtney, Antonic, A, David Howells

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.


Publication title

Brain Research Bulletin








Tasmanian School of Medicine


Elsevier Science

Place of publication

United States

Rights statement

Copyright 2019 Published by Elsevier Inc.

Repository Status

  • Restricted

Socio-economic Objectives

Treatment of human diseases and conditions

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