Therapeutic intraspinal microstimulation improves forelimb function after cervical contusion injury

Abstract

Objective Intraspinal microstimulation (ISMS) is a promising method for activating the spinal cord distal to an injury. The objectives of this study were to examine the ability of chronically implanted stimulating wires within the cervical spinal cord to (1) directly produce forelimb movements, and (2) assess whether ISMS stimulation improved subsequent volitional control of paretic extremities following injury. Approach We developed a technique for implanting intraspinal stimulating electrodes within the cervical spinal cord segments C6-T1 of Long-Evans rats. Beginning 4 weeks after a severe cervical contusion injury at C4–C5, animals in the treatment condition received therapeutic ISMS 7 hours/day, 5 days/week for the following 12 weeks. Main Results Over 12 weeks of therapeutic ISMS, stimulus-evoked forelimb movements were relatively stable. We also explored whether therapeutic ISMS promotes recovery of forelimb reaching movements. Animals receiving daily therapeutic ISMS performed significantly better than unstimulated animals during behavioral tests conducted without stimulation. Quantitative video analysis of forelimb movements showed that stimulated animals performed better in the movements reinforced by stimulation, including extending the elbow to advance the forelimb and opening the digits. While threshold current to elicit forelimb movement gradually increased over time, no differences were observed between chronically stimulated and unstimulated electrodes suggesting that no additional tissue damage was produced by the electrical stimulation. Significance The results indicate that therapeutic intraspinal stimulation delivered via chronic microwire implants within the cervical spinal cord confers benefits extending beyond the period of stimulation, suggesting future strategies for neural devices to promote sustained recovery after injury.

Targeted, activity-dependent spinal stimulation produces long-lasting motor recovery in chronic cervical spinal cord injury

“…Without stimulation, however, even intense physical retraining may be incapable of reliably activating motoneurons below the lesion, limiting activity-dependent plasticity and likely, resulting in limited recovery. In agreement with this notion, open-loop ISMS has been shown to improve reaching performance over RT only (17) in rats that were ostensibly more severely impaired than our rats. Because our hemicontusion model is defined by retention of at least some volitional motoneuron activation below the lesion, physical retraining is more likely to activate spinal circuits than it would in more severe injuries.…”

“…Consistent with this notion, focal, activitydependent intracortical stimulation has recently been shown to accelerate motor recovery over focal, open-loop intracortical stimulation after mild traumatic brain injury (16). Focal but open-loop ISMS was recently shown to improve forelimb recovery after cervical SCI in rats (17) but to a much lesser extent than we Fig. 3.…”

“…It is somewhat surprising that the performance of our TOLSS cohort did not exceed that of the RT-only animals given that the efficacy of some use-dependent movement therapies increases when combined with open-loop electrical stimulation. However, previous investigations of openloop spinal stimulation have primarily focused on severe incomplete (17) or motor complete SCI (5,7,29), in which little or no descending input to motoneurons remains (i.e., volitional motor control is lost). In these cases, open-loop spinal stimulation increases overall spinal excitability and potentiates the effects of segmental circuits.…”

A Cervical Hemi-Contusion Spinal Cord Injury Model for the Investigation of Novel Therapeutics Targeting Proximal and Distal Forelimb Functional Recovery

“…18 It will be important in the future to examine fine motor function between injury severities using measures of forelimb function as we have done for this model recently. 13,14 Although not significantly different, the myelinated area of the ventral region in the 0.8 mm group tended to be less than in the 0.6 mm group. In addition, gross observation of micro-cysts by trichrome staining corroborated the likelihood of increased axonal and myelin degeneration in this region.…”

Materials considerations of implantable neuroengineering devices for clinical use

“…Current microwire electrodes are in the 30-50 lm diameter range [51,52]. Device dimensions smaller than 12 lm minimize the foreign body response which degrades long-term recordings [53,54].…”