Project ID NS-MH2023_61

ThemeNS-MH

Co Supervisor 1A IoPPN/Wolfson CARDWebsite

Co Supervisor 1B FoLSM/Centre for Human & Applied Physiological SciencesWebsite

Additional Supervisor Aminul Ahmed

Assessing stratified spinal cord injury treatment strategies using clinically relevant respiratory measures

Respiratory failure is the leading cause of morbidity and mortality following spinal cord injury (Fig 1). There currently exists no clinical treatment for this and respiratory muscle function is not typically monitored following spinal cord injury. We hypothesise that non-invasive assessment of respiratory muscle function could direct experimentally applied stratified treatment strategies ultimately leading to individualised treatments, optimised for each patient.

This project will develop novel non-invasive methods of evaluating respiratory muscle function following spinal injury in animal models using measures of systemic ventilatory activity (muscle activity and function, ventilatory capacity) assessed in clinical patients. We will determine the degree to which non-invasive measures of respiratory muscle function may be used to direct individualised spinal cord injury treatment strategies. The student will be trained in a range of cutting-edge surgical, clinical, neurophysiological, respiratory, and anatomical techniques in an inclusive research environment as part of an interdisciplinary team (Fig 1).

Year 1: Measure novel respiratory deficits using non-invasive, clinically relevant methods in animal models of spinal cord injury focussing on critical, under-researched through EMG, electrophysiology, ventilatory function, muscle function, and cell body changes.

Year 1-2: Assess whether non-invasive measures of respiratory muscle function may be used to clinically determine dysfunction (level and extent of injury) in patients with cervical and thoracic spinal cord injuries. Establish the similarities between the clinical and experimental data.

Years 3-4: Determine the degree to which non-invasive, clinically relevant measures of respiratory muscle function may be used experimentally to direct individualised treatment strategies based upon respiratory function.

Figure 1: Respiratory muscle function after spinal injury. A) Respiratory muscle function is severely compromised after spinal injury as the circuits controlling activity are severed due to B) the extensive damage that can be caused to the descending and ascending neuronal tracts. C-D) Methods to measure respiratory muscle function after spinal cord injury include respiratory muscle electromyogram (EMG) recordings (C) and airflow during tidal breathing (D) and show recovery in some experimental treatments. E-G) We use tracing and immunocytochemistry to assess the cellular changes after injury, helping to direct clinical treatments.

Representative Publications

Warren, P.M., Campanaro, C., Jacono, F.J. & Alilain, W.J. (2018) Mid-cervical spinal cord contusion causes robust deficits in respiratory parameters and pattern variability. Experimental Neurology, 306, 122-131. PMID: 29653187; PMCID: PMC6333202.

Lozano-García, M., Estrada-Petrocelli, L., Torres, A., Rafferty, G.F., Moxham, J., Jolley, C.J. & Jané R. (2019) Noninvasive Assessment of Inspiratory Muscle Neuromechanical Coupling During Inspiratory Threshold Loading. IEEE Access, vol. 7, pp. 183634-183646, doi: 10.1109/ACCESS.2019.2960077.