Combined Supra- and Sub-Lesional Epidural Electrical Stimulation for Restoration of the Motor Functions after Spinal Cord Injury in Mini Pigs

Abstract

This study evaluates the effect of combined epidural electrical stimulation (EES) applied above (C5) and below (L2) the spinal cord injury (SCI) at T8–9 combined with motor training on the restoration of sensorimotor function in mini pigs. The motor evoked potentials (MEP) induced by EES applied at C5 and L2 levels were recorded in soleus muscles before and two weeks after SCI. EES treatment started two weeks after SCI and continued for 6 weeks led to improvement in multiple metrics, including behavioral, electrophysiological, and joint kinematics outcomes. In control animals after SCI a multiphasic M-response was observed during M/H-response testing, while animals received EES-enable training demonstrated the restoration of the M-response and H-reflex, although at a lower amplitude. The joint kinematic and assessment with Porcine Thoracic Injury Behavior scale (PTIBS) motor recovery scale demonstrated improvement in animals that received EES-enable training compared to animals with no treatment. The positive effect of two-level (cervical and lumbar) epidural electrical stimulation on functional restoration in mini pigs following spinal cord contusion injury in mini pigs could be related with facilitation of spinal circuitry at both levels and activation of multisegmental coordination. This approach can be taken as a basis for the future development of neuromodulation and neurorehabilitation therapy for patients with spinal cord injury.

New Therapy for Spinal Cord Injury: Autologous Genetically-Enriched Leucoconcentrate Integrated with Epidural Electrical Stimulation

“…Hind limb skeletal muscle contraction and the appearance of a consistent hematoma at the site exposed to the metal rod confirmed the onset of SCI. Moderate contusion injury in mini pigs has demonstrated consistent morphological and behavioural changes across our previous studies [ 28 , 29 , 32 , 36 ].…”

“…Post-operative care was performed to minimise animal suffering and to maintain a stable state of health and avoid post-operative complications. All animals received proper antibacterial and analgesic infusions and vitamin therapy as described previously [ 28 ]. Postoperative wound dressing and control of the implantation area was performed daily.…”

“…Recently, we translated spinal cord epidural electrical stimulation (EES) to a porcine model and further demonstrated the efficacy of supra- and sublesional EES [ 27 , 28 ]. We also demonstrated the benefits of triple gene therapy after intrathecal injection of umbilical cord blood mononuclear cells (UCBC) simultaneously transduced with adenoviral vectors (Ad5) carrying the genes encoding for endothelial growth factor (VEGF), glial cell line-derived neurotrophic factor (GDNF), and neural cell adhesion molecule (NCAM) [ 29 , 30 ].…”

Clinical guidelines for neurorestorative therapies in spinal cord injury (2021 China version)

“…The nervous system relies on electrical signals for information transmission and local electrical stimulation can improve and induce axon regrowth [101,[106][107][108]. Four categories of electrical stimulation can be used [101].…”

Bone Stress-Strain State Evaluation Using CT Based FEM

“…The animals were sacrificed on the 8th week after a spinal cord injury (SCI). The euthanasia was performed under deep anesthesia by overdosing on an inhalational narcosis agent (Isoflurane) (Fadeev et al, 2020). The bones of the fore and hind limbs were extracted.…”