Combined chronic theta burst stimulation of motor cortex and trans-spinal direct current stimulation in rats promote coticospinal tract outgrowth caudal to a cervical spinal contusion and motor recovery

Authors:
M. SHINOZAKI1, *N. ZAREEN2, D. RYAN2, H. ALEXANDER2, S. NAEEM3, J. H. MARTIN4;
1Keio Univ. Sch. of Med., Tokyo, Japan; 2Physiology, Pharmacol. and Neurosci., 3Sophie Davis/CUNY Sch. of Med., 4The Grad. Center, CUNY, NY, The City Col. of the City Univ. of NY, New York, NY

An important strategy for promoting motor function after SCI is to augment sprouting of the spared axons of motor pathways. We showed in a rat pyramidal tract lesion model that motor cortex (M1) electrical stimulation augments sprouting of spared corticospinal tract (CST) axons and promotes motor recovery (Carmel et al, 2010). In the present study, we translated M1 stimulation to a moderate cervical contusion injury. We modified our published M1 stimulation protocol and used an intermittent theta burst electrical stimulation (iTBS) pattern. We combined iTBS with spinal cord cathodal DC stimulation to co-activate spinal circuits during M1 stimulation, based on our recent pyramidal tract lesion study (Song et al 2016). We examined CST axonal labeling caudal to the injury and several behavioral outcomes in 2 animal groups: injury only (n=14); injury + combined iTBS and cervical spinal DC stimulation (n=13). Bilateral contusions (Infinite Horizons; 200kdyn) were made at the C4 level. Stimulation began 7 days after injury and continued for 10 days for 30 minutes daily. iTBS was delivered through epidural electrodes bilaterally over forelimb M1 and cervical cathodal DC stimulation, through cutaneous electrodes. Analyses were done blind. There were no differences in lesion volume between the two groups. Nor were there differences in the number of spared CST axons in the white matter for the two groups. We measured total CST axon length and axon varicosity number within the C6 gray matter. As expected, for both groups gray matter axon length increased as the number of spared CST axons in the white matter increased. However, this relationship was greater for the stimulated group, where there was approximately a 2-fold increase in axon length per spared white matter CST axon. A similar increase in CST axon varicosities (ie., presynaptic sites) was observed for the stimulated compared with non-stimulated group. Von Frey hair testing revealed no change in either group, relative to uninjured controls. For the IBB test, there was no difference in initial post-injury scores for the two groups and only the stimulated group showed a significant improvement compared with the non-stimulated group (non-stimulated: 7.4%; paired t-test; p=0.31; stimulated: 17.7%; p=0.009). Analyses are in progress to determine treatment effect on locomotion (horizontal ladder walking and treadmill). Our findings show that combined M1 and spinal cord cathodal DC stimulation promoted spared CST axonal outgrowth and significantly improved forepaw manipulation skills after a moderate cervical contusion injury.

Disclosures
M. Shinozaki: None. N. Zareen: None. D. Ryan: None. H. Alexander: None. S. Naeem: None. J.H. Martin: None.

Link Session 059 – Training, Rehabilitation, and Repair: Spinal Cord Injury Recovery

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