An Imposed Oscillating Electrical Field Improves the Recovery of Function in Neurologically Complete Paraplegic Dogs

Abstract

We show that an applied electric field in which the polarity is reversed every 15 minutes can improve the outcome from severe, acute spinal cord injury in dogs. This study utilized naturally injured, neurologically complete paraplegic dogs as a model for human spinal cord injury. The recovery of paraplegic dogs treated with oscillating electric field stimulation (OFS) (approximately 500 to 600 microV/mm; n = 20) was compared with that of sham-treated animals (n = 14). Active and sham stimulators were fabricated in West Lafayette, Indiana. They were coded, randomized, sterilized, and packaged in Warsaw, Indiana, and returned to Purdue University for blinded surgical implantation. The stimulators were of a previously unpublished design and meet the requirements for phase I human clinical testing. All dogs were treated within 18 days of the onset of paraplegia. During the experimental applications, all received the highest standard of conventional management, including surgical decompression, spinal stabilization (if required), and acute administration of methylprednisolone sodium succinate. A radiologic and neurologic examination was performed on every dog entering the study, the latter consisting of standard reflex testing, urologic tests, urodynamic testing, tests for deep and superficial pain appreciation, proprioceptive placing of the hind limbs, ambulation, and evoked potential testing. Dogs were evaluated before and after surgery and at 6 weeks and 6 months after surgery. A greater proportion of experimentally treated dogs than of sham-treated animals showed improvement in every category of functional evaluation at both the 6-week and 6-month recheck, with no reverse trend. Statistical significance was not reached in comparisons of some individual categories of functional evaluation between sham-treated and OFS-treated dogs (ambulation, proprioceptive placing); an early trend towards significance was shown in others (deep pain), and significance was reached in evaluations of superficial pain appreciation. An average of all individual scores for all categories of blinded behavioral evaluation (combined neurologic score) was used to compare group outcomes. At the 6-month recheck period, the combined neurologic score of OFS-treated dogs was significantly better than that of control dogs (p = 0.047; Mann-Whitney, two-tailed).

Nerve regeneration and wound healing are stimulated and directed by an endogenous electrical field in vivo

“…Applied EFs have been shown to enhance spinal nerve regeneration in the severed dorsal columns of adult guinea pig (Borgens, 1999) and to restore some function in guinea pigs and dogs with spinal cord damage (Borgens et al, 1987;Borgens et al, 1999). In addition, the efficacy of EF therapy in treating human spinal cord injuries is currently being tested in clinical trials (see www.vet.purdue.edu/cpr/).…”

Controlling Cell Behavior Electrically: Current Views and Future Potential

“…In animals exposed to oscillating DC EF stimulation however, labeled ascending and descending axons projected to the plane of transection, and in a few cases, fibers were traced around or through the lesion (13). Oscillating EF stimulation protocols have been used also in dogs with a variety of spinal cord injuries (27,28). In animals with complete paraplegia, there was a statistically improved recovery of a range of neurological behavioral tests and in some cases the restoration of walking.…”

Chick embryonic Schwann cells migrate anodally in small electrical fields

“…As a result of either developmentally programmed leaks or wounds to an epithelium, currents flow, and measured EFs of up to 100 mV mm −1 are produced in the tissues near the leak (reviewed by McCaig et al (2005). EFs have also been used to enhance repair of spinal cord injuries in dogs (Borgens et al, 1999) and are being used in this regard in ongoing human clinical trials (Shapiro et al, 2005). However, the target of EFs generated in those experiments is unclear as the EF magnitudes used (0.5 mV mm −1 ) were much smaller than those required to produce a directional effect on neurons in vitro, especially mammalian neurons (Robinson and Cormie, 2007).…”