An imposed oscillating electrical field improves the recovery of function in neurologically complete paraplegic dogs.

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 The stimulators were of a previously unpublished design and meet the requirements for phase I human clinical testing.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).

[1]  A. Blight,et al.  Axonal regeneration in spinal cord injury: A perspective and new technique , 1986, The Journal of comparative neurology.

[2]  M. Schwartz,et al.  Transplantation of activated macrophages overcomes central nervous system regrowth failure , 1996, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[3]  K. R. Robinson,et al.  The distribution of free calcium in transected spinal axons and its modulation by applied electrical fields , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[4]  S. T. Simpson Intervertebral disc disease. , 1992, The Veterinary clinics of North America. Small animal practice.

[5]  C. Robertson,et al.  Inhibition of mononuclear phagocytes reduces ischemic injury in the spinal cord , 1990, Annals of neurology.

[6]  A. Blight Macrophages and inflammatory damage in spinal cord injury. , 1992, Journal of neurotrauma.

[7]  R. Borgens,et al.  Electrically mediated regeneration and guidance of adult mammalian spinal axons into polymeric channels , 1999, Neuroscience.

[8]  A. Blight,et al.  The effects of 4-aminopyridine on neurological deficits in chronic cases of traumatic spinal cord injury in dogs: a phase I clinical trial. , 1991, Journal of neurotrauma.

[9]  C. McCaig,et al.  The direction of growth of differentiating neurones and myoblasts from frog embryos in an applied electric field. , 1981, The Journal of physiology.

[10]  A. Blight,et al.  Functional recovery after spinal cord hemisection in guinea pigs: The effects of applied electric fields , 1990, The Journal of comparative neurology.

[11]  A. A. Mendez,et al.  Anesthesia influences the outcome from experimental spinal cord injury , 1990, Brain Research.

[12]  V. Perry,et al.  Macrophages and inflammation in the central nervous system , 1993, Trends in Neurosciences.

[13]  A. Blight Delayed demyelination and macrophage invasion: a candidate for secondary cell damage in spinal cord injury. , 1985, Central nervous system trauma : journal of the American Paralysis Association.

[14]  C. McCaig,et al.  Electric fields, contact guidance and the direction of nerve growth. , 1986, Journal of embryology and experimental morphology.

[15]  A. Blight,et al.  Transected dorsal column axons within the guinea pig spinal cord regenerate in the presence of an applied electric field , 1986, The Journal of comparative neurology.

[16]  R B Borgens,et al.  Enhanced spinal cord regeneration in lamprey by applied electric fields. , 1981, Science.

[17]  P. Gambardella Dorsal Decompressive Laminectomy for Treatment of Thoracolumbar Disc Disease in Dogs: A Retrospective Study of 98 Cases , 1980 .

[18]  C. McCaig Dynamic aspects of amphibian neurite growth and the effects of an applied electric field. , 1986, The Journal of physiology.

[19]  Riyi Shi,et al.  Mammalian Cortical Astrocytes Align Themselves in a Physiological Voltage Gradient , 1994, Experimental Neurology.

[20]  R. Borgens,et al.  The effect of an applied electric field on macrophage accumulation within the subacute spinal injury. , 1999, Restorative Neurology and Neuroscience.

[21]  R B Borgens,et al.  Behavioral recovery induced by applied electric fields after spinal cord hemisection in guinea pig. , 1987, Science.

[22]  D. Wolfe,et al.  Preclinical trial of 4-aminopyridine in patients with chronic spinal cord injury , 1993, Paraplegia.

[23]  M. Cohen,et al.  Modification of retrograde degeneration in transected spinal axons of the lamprey by applied DC current , 1983, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[24]  R. Borgens,et al.  The Responses of Mammalian Spinal Axons to an Applied DC Voltage Gradient , 1997, Experimental Neurology.

[25]  J. Cook,et al.  Effects of applied electric fields on clinical cases of complete paraplegia in dogs. , 1993, Restorative neurology and neuroscience.

[26]  M. Poo,et al.  Orientation of neurite growth by extracellular electric fields , 1982, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[27]  J. D. Feldman,et al.  Directional protrusive pseudopodial activity and motility in macrophages induced by extracellular electric fields. , 1982, Cell motility.

[28]  H. Hansen A pathologic-anatomical study on disc degeneration in dog, with special reference to the so-called enchondrosis intervertebralis. , 1952, Acta orthopaedica Scandinavica. Supplementum.

[29]  A. Blight,et al.  4-Aminopyridine in chronic spinal cord injury: a controlled, double-blind, crossover study in eight patients. , 1993, Journal of neurotrauma.

[30]  C. McCaig Spinal neurite reabsorption and regrowth in vitro depend on the polarity of an applied electric field. , 1987, Development.