Traumatic Brain Injury (TBI) is a major public health issue with over 10m incidents resulting in death or in hospitalisation annually occurring worldwide. In Europe, an average incidence of 235/100,000 per year is estimated, with most countries experiencing an incidence in the range of 150-300/100,000, leading to a direct healthcare cost of EUR2.9b per year. The World Health Organization estimates that TBI will surpass many diseases as the major cause of death and disability by 2020. The other constituent of the central nervous system is the spinal cord. Damage to the spinal cord, or Spinal Cord Injury (SCI), thus shares many similarities with TBI, but also independently leads to pain and/or motor impairments ranging from incontinence to paralysis. In addition to potentially occurring simultaneously with TBI in many situations, mild SCI alone can cost in the US as much as $334,170 the first year followed by $40,589 the subsequent years. Severe SCIs reach the staggering figure of $1m for the first year alone. In the UK, this corresponds to an overall cost of £1b per year. A direct consequence of TBI and SCI, but of a much wider scope, pain management is discretely posing itself as one of the most important healthcare costs in the UK, reaching an evaluated £774m in direct cost and £4,338m in employment related cost for back pain alone in 1998, which, extrapolated to this decade, implies a total current cost of back pain in excess of £10b a year.
The recent increase in the number of research campaigns on TBI and SCI has drastically improved the understanding of the coupled role of micromechanics and electrophysiology at the neuron level. More particularly, the PI of this proposal has focussed his recent research on the development of in silico models aimed at capturing the electrophysiological alterations of neurons when submitted to a mechanical insult. In parallel to this, recent findings suggesting a direct coupling between mechanical vibration and electrical pulses in healthy neuron action potential propagation open the door to a new series of evolution for this simulation platform, as well as potentially a novel approach for the understanding of TBI and SCI. However, the intrinsic relationship between mechanical vibrations (among which ultrasounds) and their biophysical implications is still widely ignored in this context. Said otherwise, whereas the effect of mechanical damage on the neuronal functional properties is currently heavily studied, the intrinsic coupling between mechanics and electrophysiology in healthy neurons is still not fully understood. As a direct consequence, the effect of functional alteration due to a mechanical insult on the vibrational mechanical properties of a neuron has so far been fully ignored.
NeuroPulse thus aims at developing and utilising state of the art modelling approaches for the study of electrophysiological and mechanical coupling in a healthy and mechanically damaged axon, nerve and eventually spinal cord and brain white matter tract. The resulting in silico platform will be calibrated and validated by means of a comprehensive experimental programme in collaboration with the Department of Physics of the University of Oxford. Two teams of clinical project partners in Oxford and Cambridge will participate to the analysis of the results for direct applications in a clinical setting. More specifically, the project will aim at a) evaluating the role of this newly identified electrophysiological-mechanical coupling in pulses in TBI/SCI related functional deficits and, as a pilot application, b) at posing the bases for the design of a device leveraging this coupling for spinal cord pain management by cancelling effect (and reversibly, for signal enhancement). Both objectives will considerably benefit the medical community in the diagnosis, prognosis, and treatment of TBI and SCI, while providing new avenues for non-invasive electrophysiological control.
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