Abstract
A mid-thoracic spinal cord injury (SCI) severely impairs activation of the lower limb sensorimotor spinal networks, leading to paralysis. Various neuromodulatory techniques including electrical and pharmacological activation of the spinal networks have been successful in restoring locomotor function after SCI. We hypothesized that the combination of self-training in a natural environment with epidural stimulation (ES), quipazine (Quip), and strychnine (Strych) would result in greater activity in a cage environment after paralysis compared to either intervention alone. To assess this, we developed a method measuring and characterizing the chronic EMG recordings from tibialis anterior (TA) and soleus (Sol) muscles while rats were freely moving in their home cages. We then assessed the relationship between the change in recorded activity over time and motor-evoked potentials (MEPs) in animals receiving treatments. We found that the combination of ES, Quip, and Strych (sqES) generated the greatest level of recovery followed by ES + Quip (qES) while ES + Strych (sES) and ES alone showed least improvement in recorded activity. Further, we observed an exponential relationship between late response (LR) component of the MEPs and spontaneously generated step-like activity. Our data demonstrate the feasibility and potential importance of quantitatively monitoring mechanistic factors linked to activity-dependence in response to combinatorial interventions compared to individual therapies after SCI.
Highlights
To test the validity of the task recognition algorithm derived from the relative difference signal, the point of change from flexion phase to extension phase during a “step-like” event was logged
The onset and completion of a step-like or rest event for each limb was logged to a millisecond precision
We developed a method for identifying spinal rat’s hindlimb stepping like activity based on EMG patterns recorded from the Sol and tibialis anterior (TA) to determine the effects of multi-modal neuromodulation on spontaneous locomotor activity in standard individual housing cages
Summary
Numerous studies of different animal models of spinal cord injury (SCI) have demonstrated that modulating the physiological states of spinal networks, pharmacologically and electrically and in combination with motor training enables improved motor performance (Edgerton et al, 2004; Ichiyama et al, 2005; Gerasimenko et al, 2008; Lavrov et al, 2008; Courtine et al, 2009; Harkema et al, 2011; Rossignol and Frigon, 2011; Gad et al, 2013a,b; Angeli et al, 2014; Gerasimenko Y. et al, 2015; Capogrosso et al, 2016; Formento et al, 2018; Gill et al, 2018). We explored the effects of long-term sub-motor threshold ES in rats with complete mid-thoracic spinal transections (Gad et al, 2013a). These data demonstrated that when rats received sub-motor threshold ES moved around their home cages five times more than when they were not receiving ES, demonstrating the possibility to use ES to enable “self-training” in an environment while patients could be performing routine activities of daily living
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
