Effects of combining electrical stimulation with BDNF gene transfer on the regeneration of crushed rat sciatic nerve

Alrashdan, Mohammad S.; Sung, Mi-Ae; Kwon, Yunhee Kim; Chung, Hun-Jong; Kim, Sung-June; Lee, Jong-Ho

doi:10.1007/s00701-011-1054-x

Cited by 38 publications

(24 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It has recently been shown that BDNF induces neuropathological recovery in the nerve crush model [47]. Despite our results indicating that in vivo BM‐MSC TERT‐EGFP act through a neurotrophin‐independent mechanism, we assessed whether the same effect would be observed in Twitcher mice.…”

Section: Resultsmentioning

confidence: 87%

Systemic Delivery of Bone Marrow-Derived Mesenchymal Stromal Cells Diminishes Neuropathology in a Mouse Model of Krabbe's Disease

et al. 2011

View full text Add to dashboard Cite

In Krabbe's disease, a demyelinating disorder, add-on strategies targeting the peripheral nervous system (PNS) are needed, as it is not corrected by bone-marrow (BM) transplantation. To circumvent this limitation of BM transplantation, we assessed whether i.v. delivery of immortalized EGFP+ BM-derived murine mesenchymal stromal cells (BM-MSCTERT-EGFP) targets the PNS of a Krabbe's disease model, the Twitcher mouse. In vitro, BM-MSCTERT-EGFP retained the phenotype of primary BM-MSC and did not originate tumors upon transplantation in nude mice. In vivo, undifferentiated EGFP+ cells grafted the Twitcher sciatic nerve where an increase in Schwann cell precursors and axonal number was detected. The same effect was observed on BM-MSCTERT-EGFP i.v. delivery following sciatic nerve crush, a model of axonal regeneration. Reiterating the in vivo findings, in a coculture system, BM-MSCTERT-EGFP induced the proliferation of Twitcher-derived Schwann cells and the neurite outgrowth of both Twitcher-derived neurons and wild-type neurons grown in the presence of psychosine, the toxic substrate that accumulates in Krabbe's disease. In vitro, this neuritogenic effect was blocked by K252a, an antagonist of Trk receptors, and by antibody blockage of brain derived neurotrophic factor, a neurotrophin secreted by BM-MSCTERT-EGFP and induced in neighboring Schwann cells. In vivo, BM-MSCTERT-EGFP surmounted the effect of K252a, indicating their ability to act through a neurotrophin-independent mechanism. In summary, i.v. delivery of BM-MSCTERT-EGFP exerts a multilevel effect targeting neurons and Schwann cells, coordinately diminishing neuropathology. Therefore, to specifically target the PNS, MSC should be considered an add-on option to BM transplantation in Krabbe's disease and in other disorders where peripheral axonal loss occurs.

show abstract

Section: Resultsmentioning

confidence: 87%

Systemic Delivery of Bone Marrow-Derived Mesenchymal Stromal Cells Diminishes Neuropathology in a Mouse Model of Krabbe's Disease

et al. 2011

View full text Add to dashboard Cite

show abstract

“…This finding indicated that the diabetic rats in our study underwent chronic subthreshold stimulation, because the fixed 10 μA intensity utilized in this study was lower than the threshold. Several studies have reported that monophasic stimulation pulses combined with a subthreshold stimulation intensity (1-10 μA) constituted an optimal ES parameter combination that successfully facilitated neuronal cell growth in transected sciatic nerves, as evidenced by a more mature nerve structure with a smaller cross-sectional area, more myelinated fibers, higher axon density, and a higher ratio of blood vessels to total nerve area compared with that in control groups [21,[30][31][32]. Although the pudendal nerve was not crushed or transected in our study, the same stimulation parameters (i.e.…”

Section: Discussionmentioning

confidence: 99%

Chronic pudendal neuromodulation using an implantable microstimulator improves voiding function in diabetic rats

et al. 2016

View full text Add to dashboard Cite

Abtract Objective. Few studies have investigated the feasibility of using chronic pudendal neuromodulation for improving voiding function in patients with diabetes who are also experiencing urinary retention. The present study investigated the effects of chronic electrical stimulation (ES) of the sensory branch of the pudendal nerve on voiding function in diabetic rats. Approach. A custom-made implantable microstimulation system was designed and manufactured for chronic implantation in normal control (NC) and diabetic rats. After three or six weeks of pudendal neuromodulation, the intravesical pressure, external urethral sphincter electromyograms (EUS-EMGs), and urine flow rate (UFR) of all rats were simultaneously recorded to assess the effects of chronic pudendal ES on voiding function. Morphological changes in pudendal axons were assessed through hematoxylin and eosin (H&E) staining. Results. Abnormal cystometric measurements, including an increased volume threshold, contraction amplitude, and residual volume (RV) as well as a decreased burst period (BP) indicated voiding dysfunction in the diabetic rats with sham ES for three or six weeks. However, real ES for three or six weeks reversed these abnormal results; these parameters became similar to those of the NC rats and, consequently, voiding efficiency (VE) increased significantly from 17%–45% to 51%–57%. The cross-sectional area and axonal density of the pudendal nerve decreased in all the diabetic rats with sham ES for six weeks; however, these values increased significantly after real ES for six weeks. Significance. This study demonstrated the feasibility of using chronic pudendal neuromodulation for improving voiding function in diabetic rats. These results may facilitate the development of an advanced neural prosthesis for restoring bladder function in clinical settings.

show abstract

“…29–31 Furthermore, a combination of strategies, such as multiple growth factors, electrical stimulation with gene transfer, and implanted stem cells as an adjuvant therapy with growth factors, have been utilized for the improved recovery of injured nerves. 32–34 …”

Section: Introductionmentioning

confidence: 99%

“…[29][30][31] Furthermore, a combination of strategies, such as multiple growth factors, electrical stimulation with gene transfer, and implanted stem cells as an adjuvant therapy with growth factors have been utilized for the improved recovery of injured nerves. [32][33][34] Various types of synthetic and natural materials have been studied in the field of biomedical engineering to improve tissue growth, ability, and regeneration, [35][36][37] and silk biomaterial has demonstrated biocompatibility with peripheral nervous tissue repair. [38][39][40][41][42][43][44] Silk can be processed into many material formats such as scaffolds, films, gels, fibers, hollow tubes, and microstructures [45][46][47][48] and is fully degradable to amino acids, thus avoiding complications such as nerve compression and chronic inflammation.…”

Section: Introductionmentioning

confidence: 99%

Neural responses to electrical stimulation on patterned silk films

Hronik-Tupaj

Raja

Tang-Schomer

et al. 2013

J Biomedical Materials Res

View full text Add to dashboard Cite

Peripheral nerve injury is a critical issue for trauma patients. Following injury, incomplete axon regeneration or misguided axon innervation into tissue will result in loss of sensory and motor functions. The objective of this study was to examine axon outgrowth and axon alignment in response to surface patterning and electrical stimulation. To accomplish our objective, metal electrodes with dimensions of 1.5 mm × 4 cm, were sputter coated onto micropatterned silk protein films, with surface grooves 3.5 μm wide × 500 nm deep. P19 neurons were seeded on the patterned electronic silk films and stimulated at 120 mV, 1 kHz, for 45 minutes each day for 7 days. Responses were compared to neurons on flat electronic silk films, patterned silk films without stimulation, and flat silk films without stimulation. Significant alignment was found on the patterned film groups compared to the flat film groups. Axon outgrowth was greater (p < 0.05) on electronic films on day 5 and day 7 compared to the unstimulated groups. In conclusion, electrical stimulation, at 120 mV, 1 kHz, for 45 minutes daily, in addition to surface patterning, of 3.5 μm wide × 500 nm deep grooves, offered control of nerve axon outgrowth and alignment.

show abstract

Effects of combining electrical stimulation with BDNF gene transfer on the regeneration of crushed rat sciatic nerve

Abstract: Both the ES and the BDNF-Ad treatments were effective techniques enhancing the sciatic nerve regeneration following a crush injury in rats. Nevertheless, the combined treatment with ES and BDNF-Ad produces neither a synergistic effect nor an improvement in this injury model.

Cited by 38 publications

References 31 publications

Systemic Delivery of Bone Marrow-Derived Mesenchymal Stromal Cells Diminishes Neuropathology in a Mouse Model of Krabbe's Disease

Systemic Delivery of Bone Marrow-Derived Mesenchymal Stromal Cells Diminishes Neuropathology in a Mouse Model of Krabbe's Disease

Chronic pudendal neuromodulation using an implantable microstimulator improves voiding function in diabetic rats

Neural responses to electrical stimulation on patterned silk films

Contact Info

Product

Resources

About