Differential susceptibility of human neural progenitors and neurons to ischaemic injury
Autor: | Ye Liu, Ana Antonic, Emma D. Eaton, Anna E. Michalska, Jo-Maree Courtney, Mirella Dottori, David W. Howells |
---|---|
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Programmed cell death Cell Survival Neurogenesis Apoptosis Biology Pharmacology Neuroprotection 03 medical and health sciences 0302 clinical medicine Neural Stem Cells medicine Humans Noggin Progenitor cell Cells Cultured Neurons Cell Death General Neuroscience medicine.disease Embryonic stem cell Cell Hypoxia carbohydrates (lipids) Oxygen 030104 developmental biology Glucose nervous system Reperfusion Injury Stem cell Reperfusion injury 030217 neurology & neurosurgery Signal Transduction |
Zdroj: | Brain research bulletin. 156 |
ISSN: | 1873-2747 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |