Experimental Multi-Physics Measurement of Neuronal Responses under Trauma

In traumatic brain injuries (TBIs) or spinal cord injuries (SCIs), neural tissue and thus axons are subjected to a range of damaging strains and strain rates. These injuring mechanical causes are translated into biochemical and biological alterations and/or responses. Despite extensive experimental campaigns, these mechanisms remain unclear. For instance, it is still not clear how injuring mechanical causes are transferred into electrophysiological alterations, affect action potential propagation, and ultimately change cell behaviour. Moreover the specific microscale mechanisms leading to brain or spinal cord injury are still unknown, and the role of the external loading conditions are yet to be identified. One major obstacle is that experimental campaigns on neurons remain highly challenging. Recent studies show that acute neurophysiological changes not only occur immediately after injury but can also be observable through secondary mechanisms up to a few days later. Therefore electrophysiological properties and mechanical deformations should be monitored simultaneously during and after injury at the cell level. To address these issues we have set up a multi-functional patch-clamp electrophysiology rig which not only enables measurement of electrophysiological properties in parallel with mechanical loading but also provides means for applying various, yet specific, loading conditions reliably and repeatedly. The proposed experimental approach will enhance our understanding of electrophysiological-mechanical coupling in neurons, and more direct damages such as in traumatic brain injuries. Such approach will promote the technology transfer from basic and pre-clinical findings into clinical applications and consequently, medical treatment or prevention.