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.

Keywords: epidural electrical stimulation; mini pigs; spinal cord injury; translesional network.

Figure 1

Motor evoked response potentials (MEP) in soleus muscle during spinal cord stimulation. (a)—MEP in soleus muscle during stimulation at the cervical segment C5 before spinal cord injury (SCI); (b)—MEP in soleus muscle during stimulation at C5 segment 14 days after SCI; (c)—comparison between the different parameters of MEP in soleus muscle during stimulation at cervical segment C5; (d)—responses in soleus muscle during stimulation at the lumbar segment L2 before SCI; (e)—responses in soleus muscle during stimulation at the lumbar segment L2 14 days after SCI; (f)—comparison between the different parameters of early response (ER), middle response (MR), and late response (LR) in soleus muscle during stimulation of at the lumbar segment L2. S—stimulus. Data obtained for each animal are presented as points, bars represent group-wise average values.

Figure 2

The responses in soleus muscle induced by sciatic nerve stimulation. (a)—the response of soleus muscle before SCI; (b)—response of soleus muscle 8 weeks after SCI in SCI group; (c)—response of soleus muscle 8 weeks after SCI in SCI-ES (electrical stimulation) group; (d)—comparison between the different parameters of M-response and H-reflex. S—stimulus. Responses in soleus muscle recorded before SCI (before SCI), after SCI (SCI), and in SCI + EES (epidural electrosimulation) group (SCI-EES).

Figure 3

Analysis of the movements in the mini pig hind limbs. (a)—kinematics analysis of the movements in the joins of the hind limbs (average of 5 steps): the range of motion in hind limbs before SCI (before SCI), after SCI (SCI), and in group with SCI + EES on a treadmill (SCI-EES). SCI + EES on treadmill + EES, the range of movement in hind limb joints during a motor performance with EES in SCI-EES. (b) motor activity in mini pig after spinal cord injury assessed with PTIBS scale: SCI–PTIBS (Porcine Thoracic Injury Behavioral Scale) assessment in SCI group; SCI + EES−PTIBS assessment in SCI−EES group.