Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Neurosurgical Review
Published in: Neurosurgical Review 4/2019

01-12-2019 | Somatosensory Evoked Potential | Review

Weak direct current (DC) electric fields as a therapy for spinal cord injuries: review and advancement of the oscillating field stimulator (OFS)

Author: Jianming Li

Published in: Neurosurgical Review | Issue 4/2019

Login to get access

Abstract

Traumatic injury to the spinal cord remains a catastrophic event that has lifelong consequences. While decades of research have elucidated much of the pathophysiology associated with spinal cord injury (SCI), there still remains no clinically approved treatments for restoring lost sensorimotor function. The traditional dogma suggests central nervous system (CNS) neurons do not regenerate after injury but active areas of research aim to overcome this biological bottleneck. One particular approach using low-level direct current electric fields (DC EFs) appears especially promising based on a rich set of experimental data. This review highlights the biological basis for EF-induced regeneration and discusses the pre-clinical and clinical trials using the oscillating field stimulator (OFS)—a medical device designed to deliver DC EFs in vivo. I further report ongoing developments in our laboratory that refreshes the OFS concept with the hope of renewing interest in conducting additional clinical trials.
Footnotes
1
The NASCIS trials were a series of clinical trials beginning in 1984 that investigated the use of high-dose methylprednisolone to mitigate cellular oxidative stress and inflammation after acute SCI [52, 53]. The NASCIS II and III trials claimed some modest benefit of using MP following spinal injury. In retrospect, these studies have been widely criticized for poor experimental design, data reporting and suspect post-hoc statistical analysis [54, 55]. Nonetheless, the trials were the first of its kind and reported data that can be used as historical controls, especially in assessing the effects of spontaneous recovery
 
Literature
1.
Cao Y, Chen Y, DeVivo M (2011) Lifetime direct costs after spinal cord injury. Top Spinal Cord Inj Rehabil 16(4):10–16CrossRef
2.
Bracken MB, Collins WF, Freeman DF, Shepard MJ, Wagner FW, Silten RM, Hellenbrand KG, Ransohoff J, Hunt WE, Perot PL Jr (1984) Efficacy of methylprednisolone in acute spinal cord injury. JAMA 251(1):45–52CrossRefPubMed
3.
Bracken MB, Shepard MJ, Holford TR, Leo-Summers L, Aldrich EF, Fazl M, Fehlings MG, Herr DL, Hitchon PW, Marshall LF, Nockels RP, Pascale V, Perot PL Jr, Piepmeier J, Sonntag VK, Wagner F, Wilberger JE, Winn HR, Young W (1998) Methylprednisolone and neurological function 1 year after spinal cord injury. Results of the National Acute Spinal Cord Injury Study. J Neurosurg 89(5):699–706CrossRefPubMed
4.
Bracken MB, Shepard MJ, Collins WF, Holford TR, Young W, Baskin DS, Eisenberg HM, Flamm E, Leo-Summers L, Maroon J, Marshall LF, Perot PL Jr, Piepmeier J, Sonntag VKH, Wagner FC, Wilberger JE, Winn HR (1990) A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study. N Engl J Med 322(20):1405–1411CrossRefPubMed
5.
Geisler FH, Dorsey FC, Coleman WP (1991) Recovery of motor function after spinal-cord injury--a randomized, placebo-controlled trial with GM-1 ganglioside. N Engl J Med 324(26):1829–1838CrossRefPubMed
6.
Casha S, Zygun D, McGowan MD, Bains I, Yong VW, John Hurlbert R (2012) Results of a phase II placebo-controlled randomized trial of minocycline in acute spinal cord injury. Brain 135(Pt 4):1224–1236CrossRefPubMed
7.
Santamaria AJ et al (2018) Clinical and neurophysiological changes after targeted intrathecal injections of bone marrow stem cells in a C3 tetraplegic subject. J Neurotrauma
8.
9.
Bunge MB et al (2017) From transplanting Schwann cells in experimental rat spinal cord injury to their transplantation into human injured spinal cord in clinical trials. Brain Prog Res 231:107–133CrossRef
10.
Knoller N, Auerbach G, Fulga V, Zelig G, Attias J, Bakimer R, Marder JB, Yoles E, Belkin M, Schwartz M, Hadani M (2005) Clinical experience using incubated autologous macrophages as a treatment for complete spinal cord injury: phase I study results. J Neurosurg Spine 3(3):173–181CrossRefPubMed
11.
Feron F et al (2005) Autologous olfactory ensheathing cell transplantation in human spinal cord injury. Brain 128(Pt 12):2951–2960CrossRefPubMed
12.
Mackay-Sim A, Feron F, Cochrane J, Bassingthwaighte L, Bayliss C, Davies W, Fronek P, Gray C, Kerr G, Licina P, Nowitzke A, Perry C, Silburn PAS, Urquhart S, Geraghty T (2008) Autologous olfactory ensheathing cell transplantation in human paraplegia: a 3-year clinical trial. Brain 131(Pt 9):2376–2386CrossRefPubMedPubMedCentral
13.
James ND, McMahon SB, Field-Fote EC, Bradbury EJ (2018) Neuromodulation in the restoration of function after spinal cord injury. Lancet Neurol 17(10):905–917CrossRefPubMed
14.
McCaig CD, Rajnicek AM, Song B, Zhao M (2005) Controlling cell behavior electrically: current views and future potential. Physiol Rev 85(3):943–978CrossRefPubMed
15.
Sta Iglesia DD, Vanable JW Jr (1998) Endogenous lateral electric fields around bovine corneal lesions are necessary for and can enhance normal rates of wound healing. Wound Repair Regen 6(6):531–542CrossRefPubMed
16.
Zhao M, Song B, Pu J, Wada T, Reid B, Tai G, Wang F, Guo A, Walczysko P, Gu Y, Sasaki T, Suzuki A, Forrester JV, Bourne HR, Devreotes PN, McCaig CD, Penninger JM (2006) Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-gamma and PTEN. Nature 442(7101):457–460CrossRefPubMed
17.
Chiang M, Robinson KR, Vanable JW Jr (1992) Electrical fields in the vicinity of epithelial wounds in the isolated bovine eye. Exp Eye Res 54(6):999–1003CrossRefPubMed
18.
Borgens RB, Vanable JW Jr, Jaffe LF (1977) Bioelectricity and regeneration: large currents leave the stumps of regenerating newt limbs. Proc Natl Acad Sci U S A 74(10):4528–4532CrossRefPubMedPubMedCentral
19.
Borgens RB, Vanable JW Jr, Jaffe LF (1979) Role of subdermal current shunts in the failure of frogs to regenerate. J Exp Zool 209(1):49–56CrossRefPubMed
20.
Shi R, Borgens RB (1994) Embryonic neuroepithelial sodium transport, the resulting physiological potential, and cranial development. Dev Biol 165(1):105–116CrossRefPubMed
21.
Hotary KB, Robinson KR (1992) Evidence of a role for endogenous electrical fields in chick embryo development. Development 114(4):985–996PubMed
22.
Shi R, Borgens RB (1995) Three-dimensional gradients of voltage during development of the nervous system as invisible coordinates for the establishment of embryonic pattern. Dev Dyn 202(2):101–114CrossRefPubMed
23.
Song B, Zhao M, Forrester JV, McCaig CD (2002) Electrical cues regulate the orientation and frequency of cell division and the rate of wound healing in vivo. Proc Natl Acad Sci U S A 99(21):13577–13582CrossRefPubMedPubMedCentral
24.
Metcalf MEM, Borgens RB (1994) Weak applied voltages interfere with amphibian morphogenesis and pattern. J Exp Zool 268(4):323–338CrossRef
25.
Hotary KB, Robinson KR (1994) Endogenous electrical currents and voltage gradients in Xenopus embryos and the consequences of their disruption. Dev Biol 166(2):789–800CrossRefPubMed
26.
McCaig CD (1987) Spinal neurite reabsorption and regrowth in vitro depend on the polarity of an applied electric field. Development 100(1):31–41PubMed
27.
Jaffe LF, Poo MM (1979) Neurites grow faster towards the cathode than the anode in a steady-field. J Exp Zool 209(1):115–127CrossRefPubMed
28.
Mccaig CD (1990) Nerve branching is induced and oriented by a small applied electric-field. J Cell Sci 95:605–615PubMed
29.
Rajnicek AM, Robinson KR, McCaig CD (1998) The direction of neurite growth in a weak DC electric field depends on the substratum: contributions of adhesivity and net surface charge. Dev Biol 203(2):412–423CrossRefPubMed
30.
Borgens R (2003) Restoring function to the injured human spinal cord. Springer-Verlag, BerlinCrossRef
31.
32.
33.
Yao L, Li Y (2016) The role of direct current electric field-guided stem cell migration in neural regeneration. Stem Cell Rev 12(3):365–375CrossRef
34.
Borgens RB, Jaffe LF, Cohen MJ (1980) Large and persistent electrical currents enter the transected lamprey spinal cord. Proc Natl Acad Sci U S A 77(2):1209–1213CrossRefPubMedPubMedCentral
35.
Roederer E, Goldberg NH, Cohen MJ (1983) Modification of retrograde degeneration in transected spinal axons of the lamprey by applied DC current. J Neurosci 3(1):153–160CrossRefPubMedPubMedCentral
36.
Strautman AF, Cork RJ, Robinson KR (1990) The distribution of free calcium in transected spinal axons and its modulation by applied electrical fields. J Neurosci 10(11):3564–3575CrossRefPubMedPubMedCentral
37.
Berliocchi L, Bano D, Nicotera P (2005) Ca2+ signals and death programmes in neurons. Philos Trans R Soc Lond Ser B Biol Sci 360(1464):2255–2258CrossRef
38.
39.
Borgens RB, Blight AR, McGinnis ME (1987) Behavioral recovery induced by applied electric fields after spinal cord hemisection in guinea pig. Science 238(4825):366–369CrossRefPubMed
40.
Borgens RB, Mourey ME, Blight AR (1993) Delayed application of direct current electric fields in experimental spinal cord injuries. Restor Neurol Neurosci 5(3):173–179PubMed
41.
Borgens RB, Blight AR, McGinnis ME (1990) Functional recovery after spinal cord hemisection in guinea pigs: the effects of applied electric fields. J Comp Neurol 296(4):634–653CrossRefPubMed
42.
Fehlings MG, Tator CH, Linden RD (1988) The effect of direct-current field on recovery from experimental spinal cord injury. J Neurosurg 68(5):781–792CrossRefPubMed
43.
Fehlings MG, Tator CH (1992) The effect of direct current field polarity on recovery after acute experimental spinal cord injury. Brain Res 579(1):32–42CrossRefPubMed
44.
McGinnis ME, Murphy DJ (1992) The lack of an effect of applied d.c. electric fields on peripheral nerve regeneration in the guinea pig. Neuroscience 51(1):231–244CrossRefPubMed
45.
Borgens RB, Toombs JP, Blight AR, McGinnis M, Bauer MS, Widmer WR, Cook JR Jr (1993) Effects of applied electric fields on clinical cases of complete paraplegia in dogs. Restor Neurol Neurosci 5(5):305–322PubMed
46.
Borgens RB et al (1999) An imposed oscillating electrical field improves the recovery of function in neurologically complete paraplegic dogs. J Neurotrauma 16(7):639–657CrossRefPubMed
47.
Ruddle TL, Allen DA, Schertel ER, Barnhart MD, Wilson ER, Lineberger JA, Klocke NW, Lehenbauer TW (2006) Outcome and prognostic factors in non-ambulatory Hansen type I intervertebral disc extrusions: 308 cases. Vet Comp Orthop Traumatol 19(1):29–34CrossRefPubMed
48.
Ferreira AJ, Correia JH, Jaggy A (2002) Thoracolumbar disc disease in 71 paraplegic dogs: influence of rate of onset and duration of clinical signs on treatment results. J Small Anim Pract 43(4):158–163CrossRefPubMed
49.
Davis GJ, Brown DC (2002) Prognostic indicators for time to ambulation after surgical decompression in nonambulatory dogs with acute thoracolumbar disk extrusions: 112 cases. Vet Surg 31(6):513–518CrossRefPubMed
50.
Shapiro S, Borgens R, Pascuzzi R, Roos K, Groff M, Purvines S, Rodgers RB, Hagy S, Nelson P (2005) Oscillating field stimulation for complete spinal cord injury in humans: a phase 1 trial. J Neurosurg Spine 2(1):3–10CrossRefPubMed
51.
Shapiro S (2014) A review of oscillating field stimulation to treat human spinal cord injury. World Neurosurg 81(5–6):830–835CrossRefPubMed
52.
Bracken MB et al (1992) Methylprednisolone or naloxone treatment after acute spinal cord injury: 1-year follow-up data. Results of the second National Acute Spinal Cord Injury Study. J Neurosurg 76(1):23–31CrossRefPubMed
53.
Bracken MB, Shepard MJ, Holford TR, Leo-Summers L, Aldrich EF, Fazl M, Fehlings MG, Herr DL, Hitchon PW, Marshall LF, Nockels RP, Pascale V, Perot PL Jr, Piepmeier J, Sonntag VK, Wagner F, Wilberger JE, Winn HR, Young W (1998) Methylprednisolone or tirilazad mesylate administration after acute spinal cord injury: 1-year follow up. Results of the third National Acute Spinal Cord Injury randomized controlled trial. J Neurosurg 89(5):699–706CrossRefPubMed
54.
Coleman WP, Benzel E, Cahill DW, Ducker T, Geisler F, Green B, Gropper MR, Goffin J, Madsen PW III, Maiman DJ, Ondra SL, Rosner M, Sasso RC, Trost GR, Zeidman S (2000) A critical appraisal of the reporting of the National Acute Spinal Cord Injury Studies (II and III) of methylprednisolone in acute spinal cord injury. J Spinal Disord 13(3):185–199CrossRefPubMed
55.
Nesathurai S (1998) Steroids and spinal cord injury: revisiting the NASCIS 2 and NASCIS 3 trials. J Trauma 45(6):1088–1093CrossRefPubMed
56.
Walters BC (2010) Oscillating field stimulation in the treatment of spinal cord injury. PM R 2(12):S286–S291CrossRefPubMed
57.
Anderson KD (2004) Targeting recovery: priorities of the spinal cord-injured population. J Neurotrauma 21(10):1371–1383CrossRefPubMed
58.
Moriarty LJ, Borgens RB (2001) An oscillating extracellular voltage gradient reduces the density and influences the orientation of astrocytes in injured mammalian spinal cord. J Neurocytol 30(1):45–57CrossRefPubMed
59.
60.
61.
Hoare JI, Rajnicek AM, McCaig CD, Barker RN, Wilson HM (2016) Electric fields are novel determinants of human macrophage functions. J Leukoc Biol 99(6):1141–1151CrossRefPubMed
62.
Gensel JC, Zhang B (2015) Macrophage activation and its role in repair and pathology after spinal cord injury. Brain Res 1619:1–11CrossRefPubMed
63.
Li YC et al (2015) ARP2/3 complex is required for directional migration of neural stem cell-derived oligodendrocyte precursors in electric fields. Stem Cell Res Ther 6:41CrossRefPubMedPubMedCentral
64.
Feng JF, Liu J, Zhang XZ, Zhang L, Jiang JY, Nolta J, Zhao M (2012) Guided migration of neural stem cells derived from human embryonic stem cells by an electric field. Stem Cells 30(2):349–355CrossRefPubMedPubMedCentral
65.
Yao L, Li Y, Knapp J, Smith P (2015) Exploration of molecular pathways mediating electric field-directed Schwann cell migration by RNA-seq. J Cell Physiol 230(7):1515–1524CrossRefPubMedPubMedCentral
66.
Tator CH (2005) Phase 1 trial of oscillating field stimulation for complete spinal cord injury in humans. J Neurosurg Spine 2(1):1 discussion 1-2CrossRefPubMed
67.
Greenebaum B (2015) Calculated spinal cord electric fields and current densities for possible neurite regrowth from quasi-DC electrical stimulation. Bioelectromagnetics 36(8):564–575CrossRefPubMed
68.
Hernandez-Labrado GR et al (2011) Spinal cord direct current stimulation: finite element analysis of the electric field and current density. Med Biol Eng Comput 49(4):417–429CrossRefPubMed
69.
Ouyang H, Sun W, Fu Y, Li J, Cheng JX, Nauman E, Shi R (2010) Compression induces acute demyelination and potassium channel exposure in spinal cord. J Neurotrauma 27(6):1109–1120CrossRefPubMedPubMedCentral
Metadata
Title
Weak direct current (DC) electric fields as a therapy for spinal cord injuries: review and advancement of the oscillating field stimulator (OFS)
Author
Jianming Li
Publication date
01-12-2019
Publisher
Springer Berlin Heidelberg
Published in
Neurosurgical Review / Issue 4/2019
Print ISSN: 0344-5607
Electronic ISSN: 1437-2320
DOI
https://doi.org/10.1007/s10143-018-01068-y

Other articles of this Issue 4/2019

Neurosurgical Review 4/2019 Go to the issue

Review

Posterior epidural migration of herniated lumbar disc fragment: a literature review

Original Article

Pre-operative embolisation of spinal tumours: neither neglect the neighbour nor blindly follow the gold standard

Original Article

Clinical outcomes of symptomatic thoracic disk herniations treated surgically through minimally invasive lateral transthoracic approach

Original Article

Accuracy and revision rate of intraoperative computed tomography point-to-point navigation for lateral mass and pedicle screw placement: 11-year single-center experience in 1054 patients

ORIGINAL ARTICLE

A literature review concerning contralateral approaches to paraclinoid internal carotid artery aneurysms

Original Article

Vasospasm of the basilar artery following spontaneous SAH—clinical observations and implications for vascular research