Loading

Journal of Veterinary Medicine and Research

The Electric Fields and Neural Stem Cells in the Treatment of Neural Injury

Editorial | Open Access

  • 1. Department of Veterinary Medicine, Purdue University, USA
+ Show More - Show Less
Corresponding Authors
Department of Veterinary Medicine, Purdue University, Center for Paralysis Research, Basic Medical Sciences, Purdue University, West Lafayette, Indiana, USA
EDITORIAL

Nearly 1 of every 50 people (approximately 6 million) in the United States lives with at least some degree of paralysis. Paralysis occurs as the result of various nervous system injuries and/or neurological diseases. The research of treatment of paralysis is significant for the society. The application of electric fields (Efs) as a therapeutic strategy for the treatment of damaged nerves has been explored since the early twentieth century [1], with primary success to date being observed in amphibian, avian and mammalian models of neural injury.

Efs used in neural injuries, especially in spinal cord injury, have been studied for decades. In animal models of spinal cord injury, researchers found that artificially applied direct current electrical fields(DCEfs) increased the growth of axons after the transection of spinal cord in the larval lamprey Petromyzonmarinus [2] and in guinea pigs after transection of dorsal column axons [3]. The above studies suggest Efs play a critical role in the regeneration of neural injury. Evidence has showed that DCEfs induced neurite growth toward the cathode in Xenpus spinal neurons [4] and rat spiral ganglion neurons [5]. Pan and Borgens (2010, 2012) found that neurite growth in chick sympathetic neurons and dorsal root ganglion (DRG) was directed by DCEfs [6,7]. Neurites in both chick sympathetic neurons and DRG that were not perpendicular to the DCEfs rapidly began absorbing within minutes of exposure, and finished the absorption of the processes into the cell body within 1-3 hours. Over the next 3 hours, significant new neurite growth occurred, and was patterned perpendicular to the DCEfs. Another finding in these two studies was that the neurite orientation diminished after Efs were tuned off [6,7], supporting neurite outgrowth may be Ef-dependent. In addition to DCEfs, alternating current electrical fields (ACEfs) stimulation also affected neuronal growth and caused an increase in neurite length and better viability in PC12 cells [8]. Oscillating field stimulator (OFS), which delivers 500-600µV/mm of direct current and switch polarity every 15 minutes, can improve recovery of spinal cord injury in dogs [9]. OFS has also been used in a Phase 1 clinical trial, in which OFS was implanted into spinal cord injury patients and found improved recovery [10]. The results of Phase 1 clinical trial of OFS were found that oscillating electric field benefited spinal cord injury patients, indicating the efficacy and safety of the application of Efs. Asymmetrical alternating electrical fields (AACEfs), in which each component of the waveform, including the duration of positive and negative stimulation time as well as the relative intensity of both polarities can be adjusted, were first reported by Pan et al. in 2012 [11]. In this study, the effects of AACEfs on chick sympathetic neurons were investigated. The authors found that AACEfs induced a rapid retraction of neurites that prior to exposure were parallel/ tangential to the lines of force. The latter was determined to be less than 15° from perpendicular to the long axis of the experimental chamber (or alternately, perpendicular to the lines of force of the imposed AACEfs). These neurites retract rapidly beginning less than 5 min after exposure and began to regrow / re-extending to a preferred orientation perpendicular to the lines of force of the given AACEfs. The research by Pan et al. (2012) indicates that AACEfs direct neurite outgrowth of neurons and may be a potential therapy for neural injury. Those above in vivo and in vitro studies have built up a great support that Efs, including DCEfs, ACEfs, OFSand AACEfs, can benefit nerve system recovery after neural injuries.

Neural stem cell transplantation as a promising therapeutic strategy for promoting tissue repair after neurological diseases has been widely studied in both the central and peripheral nervous systems. Since NSCs were first isolated, neural stem cell transplantation has been broadly used in many neurological disease models, e.g. Parkinson’s disease, fimbria-fornix lesions, and spinal cord injury [12-14]. In peripheral nervous injury, NSC transplantation can induce remyelination and axon regeneration [15,16]. Many studies have shown that NSC migration, proliferation and differentiation are regulated by both external and cell-intrinsic signals, including signalling molecules [17], growth factors [18], neurotransmitters [19], transcription factors [20,21], epigenetic regulators [22,23], as well as Efs [24, 25]. Among these factors, Efs are being studied more and more during the last decades [4,8,24,26]. Efs may guide NSCs to migrate to their appropriate destination and then induce NSCs to differentiate into different neural cells. The applied DCEfs of physiological magnitudes (up to 500 mV/mm)can guide neural stem cells that are derived from adult rats [24], human embryonic stem cells [26], and fetal rats [27] to migrate towards the negative pole. Biphasic electric current, a pulsed alternating current stimulation, has been reported to increase the proliferation of NSCs and promote the NSC differentiation into neurons [28]. In the study of biphasic electric current, the authors found that NSC proliferation and differentiation were related to the magnitude of the electric current and the duration time of stimulation [28]. Matos & Cicerone (2010) studied the effects of ACEfs with different frequency (0.1-10 Hz) and strength (2, 4, and 16V/m) on NSC differentiation [20]. They found high frequency (1Hz) induced more astrocyte differentiation over neuronal differentiation and marked peak in NSC viability, but high field strength (16V/m) was more associated with neuronal differentiation, indicating NSC differentiation is related to frequency and strength of ACEfs. Based on the above literature, the characteristic of Efs (e.g. field strength and frequency/pulse) can influence NSC migration, proliferation and differentiation. AACEfs were found to direct mouse NSC migration in an unpublished study. In this study, three different formats of the AACEfs were used. In these three formats of AACEfs, the current outputs and the positive polarity duration time were same, but the negative polarity duration time and the latency, which is prior to reversal of polarity, were different. The format of AACEfs, which had the shortest polarity duration time and latency, had the optimal effect on NSC migration and NSCs migrated towards negative pole dramatically compared to other two formats of AACEfs. One of the important advantages of AACEfs is that their waveform components can be adjusted optimally based on the request of NSC status, such as migration, proliferation or differentiation.

Therefore, adjustable waveform components of the applied Efs should be a better strategy for researchers to investigate the therapy of neural injury. The combined research of AACEf and NSC would serve as a positive impact for a therapy to treat neural injuries.

Citation

pan L (2014) The Electric Fields and Neural Stem Cells in the Treatment of Neural Injury. J Vet Med Res 1(3): 1011.

REFERENCES

1. Ingvar S. Reaction of cells to the galvanic current in tissue cultures. Proc. Soc. exp. Biol. Med. 1920; 17: 198-199.

2. Borgens RB, Roederer E, Cohen MJ. Enhanced spinal cord regeneration in lamprey by applied electric fields. Science. 1981; 213: 611-617.

3. Borgens RB, Blight AR, Murphy DJ, Stewart L. Transected dorsal column axons within the guinea pig spinal cord regenerate in the presence of an applied electric field. J Comp Neurol. 1986; 250: 168- 180.

4. Patel N, Poo MM. Orientation of neurite growth by extracellular electric fields. J Neurosci. 1982; 2: 483-496.

5. Li S, Li H, Wang Z. Orientation of spiral ganglion neurite extension in electrical fields of charge-balanced biphasic pulses and direct current in vitro. Hear Res. 2010; 267: 111-118.

6. Pan L, Borgens RB. Perpendicular organization of sympathetic neurons within a required physiological voltage. Exp Neurol. 2010; 222: 161-164.

7. Pan L, Borgens RB. Strict perpendicular orientation of neural crestderived neurons in vitro is dependent on an extracellular gradient of voltage. J Neurosci Res. 2012; 90: 1335-1346.

8. Park JS, Park K, Moon HT, Woo DG, Yang HN, Park KH. Electrical pulsed stimulation of surfaces homogeneously coated with gold nanoparticles to induce neurite outgrowth of PC12 cells. Langmuir. 2009; 25: 451-457.

9. Borgens RB, Toombs JP, Breur G, Widmer WR, Waters D, Harbath AM, March P, et al.. An imposed oscillating electrical field improves the recovery of function in neurologically complete paraplegic dogs. J Neurotrauma. 1999;16(7):639-57.

10. Shapiro S, Borgens R, Pascuzzi R, Roos K, Groff M, Purvines S, Rodgers RB. Oscillating field stimulation for complete spinal cord injury in humans: a phase 1 trial. J Neurosurg Spine. 2005; 2: 3-10.

11. Pan L, Cirillo J, Borgens RB. Neuronal responses to an asymmetrical alternating current field can mimic those produced by an imposed direct current field in vitro. 2012; 90: 1522-1532. .

12. Anton R, Kordower JH, Maidment NT, Manaster JS, Kane DJ, Rabizadeh S, Schueller SB. Neural-targeted gene therapy for rodent and primate hemiparkinsonism. Exp Neurol. 1994; 127: 207-218.

13. Martínez-Serrano A, Lundberg C, Horellou P, Fischer W, Bentlage C, Campbell K, et al. CNS-derived neural progenitor cells for gene transfer of nerve growth factor to the adult rat brain: complete rescue of axotomized cholinergic neurons after transplantation into the septum. J Neurosci. 1995; 15: 5668-5680.

14. McDonald JW, Liu XZ, Qu Y, Liu S, Mickey SK, Turetsky D, et al. Transplanted embryonic stem cells survive, differentiate and promote recovery in injured rat spinal cord. Nat Med. 1999; 5: 1410-1412.

15. Cui L, Jiang J, Wei L, Zhou X, Fraser JL, Snider BJ, et al. Transplantation of embryonic stem cells improves nerve repair and functional recovery after severe sciatic nerve axotomy in rats. Stem Cells. 2008; 26: 1356-1365.

16. Hsu SH, Su CH, Chiu IM. A novel approach to align adult neural stem cells on micropatterned conduits for peripheral nerve regeneration: a feasibility study. Artif Organs. 2009; 33: 26-35.

17. Qu Q, Sun G, Li W, Yang S, Ye P, Zhao C, et al. Orphan nuclear receptor TLX activates Wnt/beta-catenin signalling to stimulate neural stem cell proliferation and self-renewal. Nat Cell Biol. 2010; 12: 31-40.

18. Jin K, Zhu Y, Sun Y, Mao XO, Xie L, Greenberg DA. Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo. Proc Natl Acad Sci U S A. 2002; 99: 11946-11950.

19. Höglinger GU, Rizk P, Muriel MP, Duyckaerts C, Oertel WH, Caille I, et al. Dopamine depletion impairs precursor cell proliferation in Parkinson disease. Nat Neurosci. 2004; 7: 726-735.

20. Shi Y, Chichung Lie D, Taupin P, Nakashima K, Ray J, Yu RT, et al. Expression and function of orphan nuclear receptor TLX in adult neural stem cells. Nature. 2004; 427: 78-83.

21. Kohwi M, Osumi N, Rubenstein JL, Alvarez-Buylla A. Pax6 is required for making specific subpopulations of granule and periglomerular neurons in the olfactory bulb. J Neurosci. 2005; 25: 6997-7003.

22. Cheng LC, Pastrana E, Tavazoie M, Doetsch F. miR-124 regulates adult neurogenesis in the subventricular zone stem cell niche. Nat Neurosci. 2009; 12: 399-408.

23. Molofsky AV, He S, Bydon M, Morrison SJ, Pardal R. Bmi-1 promotes neural stem cell self-renewal and neural development but not mouse growth and survival by repressing the p16Ink4a and p19Arf senescence pathways. Genes Dev. 2005; 19: 1432-1437.

24. Arocena M, Zhao M, Collinson JM, Song B. A time-lapse and quantitative modelling analysis of neural stem cell motion in the absence of directional cues and in electric fields. J Neurosci Res. 2010; 88: 3267- 3274.

25. Matos MA, Cicerone MT. Alternating current electric field effects on neural stem cell viability and differentiation. 2010; 26: 664-670.

26. Feng JF, Liu J, Zhang XZ, Zhang L, Jiang JY, Nolta J, et al. Guided migration of neural stem cells derived from human embryonic stem cells by an electric field. 2012; 30: 349-355.

27. Meng X, Arocena M, Penninger J, Gage FH, Zhao M, Song B. PI3K mediated electrotaxis of embryonic and adult neural progenitor cells in the presence of growth factors. 2011; 227: 210-217.

28. Chang KA, Kim JW, Kim JA, Lee SE, Kim S, Suh WH, et al. Biphasic electrical currents stimulation promotes both proliferation and differentiation of fetal neural stem cells. 2011; 6: e18738

Received : 26 Sep 2014
Accepted : 27 Sep 2014
Published : 27 Sep 2014
Journals
Annals of Otolaryngology and Rhinology
ISSN : 2379-948X
Launched : 2014
JSM Schizophrenia
Launched : 2016
Journal of Nausea
Launched : 2020
JSM Internal Medicine
Launched : 2016
JSM Hepatitis
Launched : 2016
JSM Oro Facial Surgeries
ISSN : 2578-3211
Launched : 2016
Journal of Human Nutrition and Food Science
ISSN : 2333-6706
Launched : 2013
JSM Regenerative Medicine and Bioengineering
ISSN : 2379-0490
Launched : 2013
JSM Spine
ISSN : 2578-3181
Launched : 2016
Archives of Palliative Care
ISSN : 2573-1165
Launched : 2016
JSM Nutritional Disorders
ISSN : 2578-3203
Launched : 2017
Annals of Neurodegenerative Disorders
ISSN : 2476-2032
Launched : 2016
Journal of Fever
ISSN : 2641-7782
Launched : 2017
JSM Bone Marrow Research
ISSN : 2578-3351
Launched : 2016
JSM Mathematics and Statistics
ISSN : 2578-3173
Launched : 2014
Journal of Autoimmunity and Research
ISSN : 2573-1173
Launched : 2014
JSM Arthritis
ISSN : 2475-9155
Launched : 2016
JSM Head and Neck Cancer-Cases and Reviews
ISSN : 2573-1610
Launched : 2016
JSM General Surgery Cases and Images
ISSN : 2573-1564
Launched : 2016
JSM Anatomy and Physiology
ISSN : 2573-1262
Launched : 2016
JSM Dental Surgery
ISSN : 2573-1548
Launched : 2016
Annals of Emergency Surgery
ISSN : 2573-1017
Launched : 2016
Annals of Mens Health and Wellness
ISSN : 2641-7707
Launched : 2017
Journal of Preventive Medicine and Health Care
ISSN : 2576-0084
Launched : 2018
Journal of Chronic Diseases and Management
ISSN : 2573-1300
Launched : 2016
Annals of Vaccines and Immunization
ISSN : 2378-9379
Launched : 2014
JSM Heart Surgery Cases and Images
ISSN : 2578-3157
Launched : 2016
Annals of Reproductive Medicine and Treatment
ISSN : 2573-1092
Launched : 2016
JSM Brain Science
ISSN : 2573-1289
Launched : 2016
JSM Biomarkers
ISSN : 2578-3815
Launched : 2014
JSM Biology
ISSN : 2475-9392
Launched : 2016
Archives of Stem Cell and Research
ISSN : 2578-3580
Launched : 2014
Annals of Clinical and Medical Microbiology
ISSN : 2578-3629
Launched : 2014
JSM Pediatric Surgery
ISSN : 2578-3149
Launched : 2017
Journal of Memory Disorder and Rehabilitation
ISSN : 2578-319X
Launched : 2016
JSM Tropical Medicine and Research
ISSN : 2578-3165
Launched : 2016
JSM Head and Face Medicine
ISSN : 2578-3793
Launched : 2016
JSM Cardiothoracic Surgery
ISSN : 2573-1297
Launched : 2016
JSM Bone and Joint Diseases
ISSN : 2578-3351
Launched : 2017
JSM Bioavailability and Bioequivalence
ISSN : 2641-7812
Launched : 2017
JSM Atherosclerosis
ISSN : 2573-1270
Launched : 2016
Journal of Genitourinary Disorders
ISSN : 2641-7790
Launched : 2017
Journal of Fractures and Sprains
ISSN : 2578-3831
Launched : 2016
Journal of Autism and Epilepsy
ISSN : 2641-7774
Launched : 2016
Annals of Marine Biology and Research
ISSN : 2573-105X
Launched : 2014
JSM Health Education & Primary Health Care
ISSN : 2578-3777
Launched : 2016
JSM Communication Disorders
ISSN : 2578-3807
Launched : 2016
Annals of Musculoskeletal Disorders
ISSN : 2578-3599
Launched : 2016
Annals of Virology and Research
ISSN : 2573-1122
Launched : 2014
JSM Renal Medicine
ISSN : 2573-1637
Launched : 2016
Journal of Muscle Health
ISSN : 2578-3823
Launched : 2016
JSM Genetics and Genomics
ISSN : 2334-1823
Launched : 2013
JSM Anxiety and Depression
ISSN : 2475-9139
Launched : 2016
Clinical Journal of Heart Diseases
ISSN : 2641-7766
Launched : 2016
Annals of Medicinal Chemistry and Research
ISSN : 2378-9336
Launched : 2014
JSM Pain and Management
ISSN : 2578-3378
Launched : 2016
JSM Women's Health
ISSN : 2578-3696
Launched : 2016
Clinical Research in HIV or AIDS
ISSN : 2374-0094
Launched : 2013
Journal of Endocrinology, Diabetes and Obesity
ISSN : 2333-6692
Launched : 2013
Journal of Substance Abuse and Alcoholism
ISSN : 2373-9363
Launched : 2013
JSM Neurosurgery and Spine
ISSN : 2373-9479
Launched : 2013
Journal of Liver and Clinical Research
ISSN : 2379-0830
Launched : 2014
Journal of Drug Design and Research
ISSN : 2379-089X
Launched : 2014
JSM Clinical Oncology and Research
ISSN : 2373-938X
Launched : 2013
JSM Bioinformatics, Genomics and Proteomics
ISSN : 2576-1102
Launched : 2014
JSM Chemistry
ISSN : 2334-1831
Launched : 2013
Journal of Trauma and Care
ISSN : 2573-1246
Launched : 2014
JSM Surgical Oncology and Research
ISSN : 2578-3688
Launched : 2016
Annals of Food Processing and Preservation
ISSN : 2573-1033
Launched : 2016
Journal of Radiology and Radiation Therapy
ISSN : 2333-7095
Launched : 2013
JSM Physical Medicine and Rehabilitation
ISSN : 2578-3572
Launched : 2016
Annals of Clinical Pathology
ISSN : 2373-9282
Launched : 2013
Annals of Cardiovascular Diseases
ISSN : 2641-7731
Launched : 2016
Journal of Behavior
ISSN : 2576-0076
Launched : 2016
Annals of Clinical and Experimental Metabolism
ISSN : 2572-2492
Launched : 2016
Clinical Research in Infectious Diseases
ISSN : 2379-0636
Launched : 2013
JSM Microbiology
ISSN : 2333-6455
Launched : 2013
Journal of Urology and Research
ISSN : 2379-951X
Launched : 2014
Journal of Family Medicine and Community Health
ISSN : 2379-0547
Launched : 2013
Annals of Pregnancy and Care
ISSN : 2578-336X
Launched : 2017
JSM Cell and Developmental Biology
ISSN : 2379-061X
Launched : 2013
Annals of Aquaculture and Research
ISSN : 2379-0881
Launched : 2014
Clinical Research in Pulmonology
ISSN : 2333-6625
Launched : 2013
Journal of Immunology and Clinical Research
ISSN : 2333-6714
Launched : 2013
Annals of Forensic Research and Analysis
ISSN : 2378-9476
Launched : 2014
JSM Biochemistry and Molecular Biology
ISSN : 2333-7109
Launched : 2013
Annals of Breast Cancer Research
ISSN : 2641-7685
Launched : 2016
Annals of Gerontology and Geriatric Research
ISSN : 2378-9409
Launched : 2014
Journal of Sleep Medicine and Disorders
ISSN : 2379-0822
Launched : 2014
JSM Burns and Trauma
ISSN : 2475-9406
Launched : 2016
Chemical Engineering and Process Techniques
ISSN : 2333-6633
Launched : 2013
Annals of Clinical Cytology and Pathology
ISSN : 2475-9430
Launched : 2014
JSM Allergy and Asthma
ISSN : 2573-1254
Launched : 2016
Journal of Neurological Disorders and Stroke
ISSN : 2334-2307
Launched : 2013
Annals of Sports Medicine and Research
ISSN : 2379-0571
Launched : 2014
JSM Sexual Medicine
ISSN : 2578-3718
Launched : 2016
Annals of Vascular Medicine and Research
ISSN : 2378-9344
Launched : 2014
JSM Biotechnology and Biomedical Engineering
ISSN : 2333-7117
Launched : 2013
Journal of Hematology and Transfusion
ISSN : 2333-6684
Launched : 2013
JSM Environmental Science and Ecology
ISSN : 2333-7141
Launched : 2013
Journal of Cardiology and Clinical Research
ISSN : 2333-6676
Launched : 2013
JSM Nanotechnology and Nanomedicine
ISSN : 2334-1815
Launched : 2013
Journal of Ear, Nose and Throat Disorders
ISSN : 2475-9473
Launched : 2016
JSM Ophthalmology
ISSN : 2333-6447
Launched : 2013
Journal of Pharmacology and Clinical Toxicology
ISSN : 2333-7079
Launched : 2013
Annals of Psychiatry and Mental Health
ISSN : 2374-0124
Launched : 2013
Medical Journal of Obstetrics and Gynecology
ISSN : 2333-6439
Launched : 2013
Annals of Pediatrics and Child Health
ISSN : 2373-9312
Launched : 2013
JSM Clinical Pharmaceutics
ISSN : 2379-9498
Launched : 2014
JSM Foot and Ankle
ISSN : 2475-9112
Launched : 2016
JSM Alzheimer's Disease and Related Dementia
ISSN : 2378-9565
Launched : 2014
Journal of Addiction Medicine and Therapy
ISSN : 2333-665X
Launched : 2013
Annals of Public Health and Research
ISSN : 2378-9328
Launched : 2014
Annals of Orthopedics and Rheumatology
ISSN : 2373-9290
Launched : 2013
Journal of Clinical Nephrology and Research
ISSN : 2379-0652
Launched : 2014
Annals of Community Medicine and Practice
ISSN : 2475-9465
Launched : 2014
Annals of Biometrics and Biostatistics
ISSN : 2374-0116
Launched : 2013
JSM Clinical Case Reports
ISSN : 2373-9819
Launched : 2013
Journal of Cancer Biology and Research
ISSN : 2373-9436
Launched : 2013
Journal of Surgery and Transplantation Science
ISSN : 2379-0911
Launched : 2013
Journal of Dermatology and Clinical Research
ISSN : 2373-9371
Launched : 2013
JSM Gastroenterology and Hepatology
ISSN : 2373-9487
Launched : 2013
Annals of Nursing and Practice
ISSN : 2379-9501
Launched : 2014
JSM Dentistry
ISSN : 2333-7133
Launched : 2013
Author Information X