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The Effect of an Oxygen Gradient on Activation and Cellular Survival of Neuronal Networks

Hagers, L. (2024) The Effect of an Oxygen Gradient on Activation and Cellular Survival of Neuronal Networks.

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Abstract:During an ischemic stroke, oxygen and glucose deficiencies are present, due to a decrease in blood perfusion. In the core, cells are irreversibly damaged and die via necrosis within minutes as apposed to cells surrounding the core, also known as the penumbra. In the penumbra, cells remain structurally intact, but synaptic failure reduces the amount of activity. If these cells cannot be restored, due to lack of reperfusion, they die via apoptosis hours or days later. This characteristic makes the penumbra a highly targeted region for potential treatments, however the exact mechanisms behind this balance between recovery and cell death are incompletely understood. Therefore we tried to mimic a more \textit{in vivo} penumbra by modifying a previously published oxygen gradient generator and combining it with electrophysiological recordings and live fluorescent imaging of apoptotic and dead cells on neuronal cultures. During a 36 hour measurement, cells were exposed to 6 hours of normoxia, followed by 24 hours of gradient and finally another 6 hours of normoxia. The electrophysiological results showed that when the severity of hypoxia increased, the activity of the neurons decreased more rapidly. After 8 hours the activity increased back to baseline, due to disinhibition, followed by a large overshoot caused by medium evaporation. The fluorescent imaging showed that cells died from apoptosis and that this increased as the oxygen concentration decreased. If these findings are compared to previous studies where neuronal cultures were exposed to constant depths of hypoxia rather than a gradient, electrophysiological as well as the fluorescence results show similar patterns. This rejects the hypothesis that different areas in the gradient influence the behaviour of neurons in activity and survival.
Item Type:Essay (Bachelor)
Faculty:TNW: Science and Technology
Subject:42 biology
Programme:Biomedical Technology BSc (56226)
Link to this item:https://purl.utwente.nl/essays/101600
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