Establishing a microfluidic in vitro model of remote ischaemic damage in connected neuronal cultures

Ischaemic stroke is a leading cause of death and disability in the UK. A growing literature has demonstrated that damage extends beyond the core ischaemic zone into remote but connected regions of the brain, with various phenomena including axon degradation and 5-hydroxymethylcytosine (5-hmc) expression being implicated. In an effort to understand and potentially circumvent these effects, a simplified in vitro model allowing for localised oxygenglucose deprivation (OGD) in interconnected neuronal cultures would be highly valuable. In this project, the plausibility of localising OGD using an oxygen scavenger within a microfluidic device was explored. Physical characterisation of the device confirmed that this is the first in vitro model allowing for the production of compartmentalised OGD in neuronal cultures. To demonstrate the investigational possibilities this device enables, preliminary observations were made regarding the effects of both direct (somal) and remotely connected (axonal) OGD on axon degeneration, cell death, and 5-hmc expression in iPSC-derived patterned neuronal cultures. Trends were observed in these measured parameters, highlighting the need for further experimentation with the device to expand observed effects and further explore its applicability to stroke research and prevention.

Author(s): Jennifer Knight

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