Investigation of the effects of electrical stimulation on BDNF and NGF levels in the sciatic nerve injury rat model

Egemen Işık; Filiz Kazak; Ziya Yurtal; Halil Alakuş

doi:10.33988/auvfd.1424698

Research Article

Investigation of the effects of electrical stimulation on BDNF and NGF levels in the sciatic nerve injury rat model

Year 2024, Accepted Papers, 1 - 7

Egemen Işık , Filiz Kazak , Ziya Yurtal , Halil Alakuş

https://doi.org/10.33988/auvfd.1424698

Abstract

The current study aimed to investigate the effects of electrical stimulation on brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) levels in rats with sciatic nerve injury. Twenty-eight rats were divided into four groups of sham (S, n=7), electrical stimulation (ES, n=7), sciatic nerve injury (SNI, n=7) and sciatic nerve injury+electrical stimulation (SNI+ES, n=7). An experimental nerve damage model was produced by applying a closing force to compress the sciatic nerve. Electrical stimulation was applied for twenty minutes at 200 μs, 2mA, and 20 Hz for fifteen days. Enzyme-linked immunosorbent assay analysis was used to evaluate the levels of NGF and BDNF. It was shown that the SNI group had higher brain BDNF levels than the other groups, while the S group had lower brain BDNF levels than the other groups (P<0.001). The ES and SNI groups had higher serum BDNF levels than the S and SNI+ES groups (P<0.01), while the SNI group had higher brain NGF levels than the S and SNI+ES groups (P<0.05). In comparison to the S and ES groups, the serum NGF levels in the SNI and SNI+ES groups were shown to be lower (P<0.01). Following the sciatic nerve damage, it was measured that the administration of electrical stimulation resulted in an increase in brain BDNF and a decrease in serum NGF. According to this research, electrical stimulation may have an impact on the release of NGF and BDNF after sciatic nerve damage.

Keywords

Brain-derived neurotrophic factor, electrical stimulation, nerve growth factor, sciatic nerve.

Ethical Statement

This study was carried out after the animal experiment was approved by Hatay Mustafa Kemal University Local Ethics Committee (Decision number: 2019/10-5, 17/12/2019).

Supporting Institution

Hatay Mustafa Kemal University Research Fund

Project Number

20.YL.004

Thanks

This study was extracted from thesis in Biochemistry Depertment of Veterinary Medicine Faculty, Hatay Mustafa Kemal University by Egemen Isik (master’s degree student). The abstract of this study has been presented as an oral presentation in the International Symposium of Scientific Research and Innovative Studies (ISSRIS’21) 22-25 February 2021.

References

Al-Majed AA, Brushart TM, Gordon T (2000): Electrical stimulation accelerates and increases expression of BDNF and trkB mRNA in regenerating rat femoral motoneurons. Eur J Neurosci, 12, 4381-4390.
Alrashdan MS, Sung ME, Kwon YK, et al (2011): Effects of combining electrical stimulation with BDNF gene transfer on the regeneration of crushed rat sciatic nerve. Acta Neurochir, 153, 2021-2029.
Ashour FA, Elbazb AA, Sabekc NA, et al (2015): Effect of electrical stimulation and stem cells on experimentally induced peripheral nerve injury in rats. Menoufia Med J, 28, 742-747.
Bregman BS, McAtee M, Dai HN, et al (1997): Neurotrophic factors increase axonal growth after spinal cord injury and transplantation in the adult rat. Exp Neurol, 148, 475-494.
Frostick SP, Yin Q, Kemp GJ (1998): Schwann cells, neurotrophic factors, and peripheral nerve regeneration. Microsurgery, 18, 397-405.
Fu SY, Gordon T (1997): The cellular and molecular basis of peripheral nerve regeneration. Mol Neurobiol, 14, 67-116.
Gordon T, Brushart TM, Chan KM (2008): Augmenting nerve regeneration with electrical stimulation. Neurol Res, 30, 1012-1022.
Gravvanis AI, Tsoutsos DA, Tagaris GA, et al (2004): Beneficial effect of nerve growth factor-7S on peripheral nevre regeneration through inside-out vein grafts: an experimental study. Microsurgery, 24, 408-415.
Hammarberg H, Piehl F, Risling M, et al (2000): Differential regulation of trophic factor receptor mRNAs in spinal motoneurons after sciatic nerve transection and ventral root avulsion in the rat. J Comp Neurol, 426, 587–601.
Ho PR, Coan GM, Chang ET, et al (1998): Repair with collagen tubules linked with brain derived neurotrophic factor and ciliary neurotrophic factor in a rat sciatic nerve injury model. Arch Otolaryngol Head Neck Surg, 124, 761-766.
Huang J, Zhang Y, Lu L, et al (2013): Electrical stimulation accelerates nerve regeneration and functional recovery in delayed peripheral nerve injury in rats. Eur J Neurosci, 38, 3691-701.
Jung R, Ichihara K, Venkatasubramanian G, et al (2009): Chronic neuromuscular electrical stimulation of paralyzed hindlimbs in a rodent model. J Neurosci Methods, 183, 241-254.
Kanchiku T, Suzuki H, Imajo Y, et al (2015): The efficacy of neuromuscular electrical stimulation with alternating currents in the kilohertz frequency to stimulate gait rhythm in rats following spinal cord injury. Biomed Eng Online, 14:98.
Kazak F, Akalın PP, Yarım GF, et al (2021): Protective effects of nobiletin on cisplatin induced neurotoxicity in rats. Int J Neurosci, 1–7.
Kazak F, Yarım GF (2014): Neurotrophins. Kocatepe Vet J, 7, 47-57.
Kazak F, Yarım GF (2015): Brain Derived Neurotrophic Factor. Atatürk University J Vet Sci, 10, 120-129.
Knutson J, Sheffler L, Chae J (2014): Fonksiyonel Nöromuskuler Stimülasyon. Ed. Frontera W. Fiziksel Tıp ve Rehabilitasyon İlkeler ve Uygulamalar, Güneş Tıp Kitabevleri, İstanbul.
Kou Y, Wang Z, Wu Z, et al (2013): Epimedium extract promotes peripheral nerve regeneration in rats. Evid Based Complement Alternat Med, 2013, 954798.
Lee AC, Yu VM, Lowe JB 3rd, et al (2003): Controlled release of nerve growth factor enhances sciatic nerve regeneration. Exp Neurol, 184, 295-303.
Lewin SL, Utley DS, Cheng E, et al (1997): Simultaneous treatment with BDNF and CNTF after peripheral nerve transection and repair enhances rate of functional recovery compared with BDNF-treatment alone. Laryngoscope, 107, 992-999.
Lowry OH, Rosebrough NJ, Farr AL, et al (1951): Protein measurement with Folin phenol reagent. J Biol Chem, 193, 265-275.
Lu MC, Ho CY, Hsu SF, et al (2008): Effects of electrical stimulation at different frequencies on regeneration of transected peripheral nerve. Neurorehabil Neural Repair, 22, 367-373.
Meyer M, Matsuoka I, Wetmore C, et al (1992): Enhanced synthesis of brain-derived neurotrophic factor in the lesioned peripheral nerve: different mechanisms are responsible for the regulation of BDNF and NGF mRNA. J Cell Biol, 19, 45-54.
Midha R, Munro CA, Dalton PD, et al (2003): Growth factor enhancement of peripheral nerve regeneration through a novel synthetic hydrogel tube. J Neurosurg, 99, 555-565.
Ni L, Yao Z, Zhao Y, et al (2023): Electrical stimulation therapy for peripheral nerve injury. Front Neurol, 14, 1081458.
Nix WA, Hopf HC (1983): Electrical stimulation of regenerating nerve and its effect on motor recovery. Brain Res, 272, 21-25.
Obata K, Noguchi K (2006): BDNF in sensory neurons and chronic pain. Neurosci Res, 55, 1-10.
Pagnotta A, Tos P, Fornaro M, et al (2002): Neurotrophins and their receptors in early axonal regeneration along muscle-vein-combined grafts. Microsurgery, 22, 300-303.
Park BR, Hwang JH, Kim MS, et al (2004): Modulation of BDNF expression by electrical stimulation in hindlimb muscles of rats. Neurosci Res Comm, 34, 10-19.
Polat E, Dağlıoğlu E, Menekşe G, et al (2016): Neuroprotective effects of adalimumab on rats w ith experimental peripheral nerve injury: An electron microscopic and biochemical study. Ulus Travma Acil Cerrahi Derg, 22, 134138.
Shakhbazau A, Martinez JA, Xu QG, et al (2012): Evidence for a systemic regulation of neurotrophin synthesis in response to peripheral nerve injury. J Neurochem, 122, 501-511.
Sheng CY, Liang HC, Chuan TC, et al (2000): Peripheral nevre regeneration using silicone rubber chambers filled with collagen, laminin and fibronectin. Biomaterials, 21, 1541-1547.
Tyreman JG, Pettersson LME, Verge VM, et al (2008): BDNF-mediated acceleration of motor axonal regeneration by brief low frequency electrical stimulation (ES). Soc Neurosci, 33, 752-759.
Varejao AS, Melo-Pinto P, Meek MF, et al (2004): Methods for experimental functional assessment of rat sciatic nerve regeneration. Neurol Res, 26, 186-194.
Vögelin E, Baker JM, Gates J, et al (2006): Effects of local continuous release of brain derived neurotrophic factor (BDNF) on peripheral nerve regeneration in a rat model. Exp Neurol, 199, 348-353.
Wahlsten D (2011): Chapter 5 - Sample Size. In: Wahlsten, D. (ed.) Mouse Behavioral Testing. London: Academic Press.
Zhou XF, Rush RA (1996): Endogenous brain-derived neurotrophic factor is anterogradely transported in primary sensory neurons. Neuroscience, 74, 945-53.