Download PDF
J Reconstr Microsurg 2015; 31(03): 191-197
DOI: 10.1055/s-0034-1395414
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Effects of Intraperitoneally Administered Folic Acid on the Healing of Repaired Tibial Nerves in Rats

Ahmet Harma
1   Department of Orthopedics Surgery, Faculty of Medicine, Inonu University, Malatya, Turkey
,
Mehmet Sukru Sahin
2   Department of Orthopedics Surgery, Faculty of Medicine, Baskent University Alanya Hospital, Alanya, Antalya, Turkey
,
Suzan Zorludemir
3   Department of Pathology, Faculty of Medicine, Cukurova University, Adana, Turkey
› Author Affiliations
Further Information

Publication History

11 June 2014

06 September 2014

Publication Date:
25 November 2014 (online)

    Permissions and Reprints

Abstract

Background Complete nerve regeneration and clinical healing remain a challenge despite considerable advances in the treatment of peripheral nerve injuries. To improve nerve regeneration, several experimental molecular procedures have been attempted. This study aimed to investigate the effects of folic acid on peripheral nerve healing after transection and end-to-end suture repair of the tibial nerve in rats.

Methods In this study, 20 adult male Wistar Albino rats weighing 225 to 250 g were used. The right tibial nerves of 20 rats were explored, transected, and sutured using the end-to-end technique. The rats were randomly allocated to either the intraperitoneally administered folic acid group (test group) or the control group. Preoperative and 6-week postoperative neurophysiological studies were performed by the same researcher. Myelin-sheathed axons were counted.

Results The results demonstrated that the folic acid–treated group exhibited improved electromyographic results compared with the control group. Histological evaluation revealed that the axons were well preserved and that the axon quantity and density were increased in the test group compared with the control group. Quantitative results also increased in the test group compared with the control group (p = 0.001).

Conclusion In this study, 6-week intraperitoneal administration of 80 µg/kg of folic acid significantly improved peripheral nerve healing. Histological analysis of the group that received folic acid revealed increased axon myelination with little granular tissue or fibrosis. We propose that folic acid supplementation may be an effective component of peripheral nerve injury treatment.

Keywords

folic acid - peripheral nerve - nerve repair - regeneration
 

  • References

  • 1 Gordon T, Tyreman N, Raji MA. The basis for diminished functional recovery after delayed peripheral nerve repair. J Neurosci 2011; 31 (14) 5325-5334
    CrossrefPubMedGoogle Scholar
  • 2 Lundborg G, Dahlin L, Danielsen N, Zhao Q. Trophism, tropism, and specificity in nerve regeneration. J Reconstr Microsurg 1994; 10 (5) 345-354
    Article in Thieme ConnectPubMedGoogle Scholar
  • 3 Özgenel GY. Effects of hyaluronic acid on peripheral nerve scarring and regeneration in rats. Microsurgery 2003; 23 (6) 575-581
    CrossrefPubMedGoogle Scholar
  • 4 Ozgenel GY, Filiz G. Effects of human amniotic fluid on peripheral nerve scarring and regeneration in rats. J Neurosurg 2003; 98 (2) 371-377
    CrossrefPubMedGoogle Scholar
  • 5 Jesse FG. Case study: folate bioavailability, bioavailability of nutrients and other bioactive components from dietary supplements. J Nutr 2001; 131: 1376-1382
    PubMedGoogle Scholar
  • 6 Kim YI. Folate, colorectal carcinogenesis, and DNA methylation: lessons from animal studies. Environ Mol Mutagen 2004; 44 (1) 10-25
    CrossrefPubMedGoogle Scholar
  • 7 Iskandar BJ, Nelson A, Resnick D , et al. Folic acid supplementation enhances repair of the adult central nervous system. Ann Neurol 2004; 56 (2) 221-227
    CrossrefPubMedGoogle Scholar
  • 8 Frykman GK, McMillan PJ, Yegge S. A review of experimental methods measuring peripheral nerve regeneration in animals. Orthop Clin North Am 1988; 19 (1) 209-219
    PubMedGoogle Scholar
  • 9 al-Qattan MM, al-Thunyan A. Variables affecting axonal regeneration following end-to-side neurorrhaphy. Br J Plast Surg 1998; 51 (3) 238-242
    CrossrefPubMedGoogle Scholar
  • 10 Rodriguez FJ, Valero-Cabre A, Navarro X. Regeneration and functional recovery following peripheral nerve injury. Drug Discov Today 2004; 1 (2) 177-185
    PubMedGoogle Scholar
  • 11 Zhao JZ, Chen ZW, Chen TY. Nerve regeneration after terminolateral neurorrhaphy: experimental study in rats. J Reconstr Microsurg 1997; 13 (1) 31-37
    Article in Thieme ConnectPubMedGoogle Scholar
  • 12 Scharpf J, Meirer R, Zielinski M , et al. A novel technique for peripheral nerve repair. Laryngoscope 2003; 113 (1) 95-101
    CrossrefPubMedGoogle Scholar
  • 13 Matsuyama T, Mackay M, Midha R. Peripheral nerve repair and grafting techniques: a review. Neurol Med Chir (Tokyo) 2000; 40 (4) 187-199
    CrossrefPubMedGoogle Scholar
  • 14 Zhang F, Fischer KA. End-to-side neurorrhaphy. Microsurgery 2002; 22 (3) 122-127
    CrossrefPubMedGoogle Scholar
  • 15 Millesi H. Progress in peripheral nerve reconstruction. World J Surg 1990; 14 (6) 733-747
    CrossrefPubMedGoogle Scholar
  • 16 Bodine-Fowler SC, Meyer RS, Moskovitz A, Abrams R, Botte MJ. Inaccurate projection of rat soleus motoneurons: a comparison of nerve repair techniques. Muscle Nerve 1997; 20 (1) 29-37
    CrossrefPubMedGoogle Scholar
  • 17 Young C, Miller E, Nicklous DM, Hoffman JR. Nerve growth factor and neurotrophin-3 affect functional recovery following peripheral nerve injury differently. Restor Neurol Neurosci 2001; 18 (4) 167-175
    PubMedGoogle Scholar
  • 18 Madura T, Tomita K, Terenghi G. Ibuprofen improves functional outcome after axotomy and immediate repair in the peripheral nervous system. J Plast Reconstr Aesthet Surg 2011; 64 (12) 1641-1646
    CrossrefPubMedGoogle Scholar
  • 19 Rieger S, Sagasti A. Hydrogen peroxide promotes injury-induced peripheral sensory axon regeneration in the zebrafish skin. PLoS Biol 2011; 9 (5) e1000621
    CrossrefPubMedGoogle Scholar
  • 20 Yin ZS, Zhang H, Bo W, Gao W. Erythropoietin promotes functional recovery and enhances nerve regeneration after peripheral nerve injury in rats. AJNR Am J Neuroradiol 2010; 31 (3) 509-515
    CrossrefPubMedGoogle Scholar
  • 21 Ayan I, Esenkaya I, Karakaplan M , et al. The effect of human placental suspension on rat sciatic nerve healing [in Turkish]. Acta Orthop Traumatol Turc 2007; 41 (2) 140-146
    PubMedGoogle Scholar
  • 22 Saceda J, Isla A, Santiago S , et al. Effect of recombinant human growth hormone on peripheral nerve regeneration: experimental work on the ulnar nerve of the rat. Neurosci Lett 2011; 504 (2) 146-150
    CrossrefPubMedGoogle Scholar
  • 23 Luria S, Cohen A, Safran O, Firman S, Liebergall M. Immune system augmentation by glatiramer acetate of peripheral nerve regeneration-crush versus transection models of rat sciatic nerve. J Reconstr Microsurg 2013; 29 (8) 495-500
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 Konofaos P, Terzis JK. FK506 and nerve regeneration: past, present, and future. J Reconstr Microsurg 2013; 29 (3) 141-148
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Ali SA, Economides DL. Folic acid supplementation. Curr Opin Obstet Gynecol 2000; 12 (6) 507-512
    CrossrefPubMedGoogle Scholar
  • 26 Iskandar BJ, Rizk E, Meier B , et al. Folate regulation of axonal regeneration in the rodent central nervous system through DNA methylation. J Clin Invest 2010; 120 (5) 1603-1616
    CrossrefPubMedGoogle Scholar
  • 27 Wang KK, Nemeth IR, Seckel BR , et al. Hyaluronic acid enhances peripheral nerve regeneration in vivo. Microsurgery 1998; 18 (4) 270-275
    CrossrefPubMedGoogle Scholar
  • 28 Almquist EE, Smith OA, Fry L. Nerve conduction velocity, microscopic, and electron microscopy studies comparing repaired adult and baby monkey median nerves. J Hand Surg Am 1983; 8 (4) 406-410
    CrossrefPubMedGoogle Scholar
  • 29 Oh SJ. Normal values for common nerve conduction tests. In: Retfort DC, , ed. Clinical Electromyography: Nerve Conduction Studies. 2nd ed. Philadelphia, PA: Williams & Wilkins; 1993: 84-104
    Google Scholar
  • 30 de Araujo MP. Electrodiagnosis in compression neuropathies of the upper extremities. Orthop Clin North Am 1996; 27 (2) 237-244
    PubMedGoogle Scholar
  • 31 Krarup C, Archibald SJ, Madison RD. Factors that influence peripheral nerve regeneration: an electrophysiological study of the monkey median nerve. Ann Neurol 2002; 51 (1) 69-81
    CrossrefPubMedGoogle Scholar