Download PDF
J Reconstr Microsurg 2016; 32(04): 309-315
DOI: 10.1055/s-0035-1571198
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

A Time Course Study of Different Methods of Extraneural Scar Induction in a Rat Model

Leila Oriady Zanjani
1   Research Center for Neural Repair (RCNR), University of Tehran, Tehran, Iran
2   Department of Orthopedic and Trauma Surgery, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
,
Masoumeh Firouzi
1   Research Center for Neural Repair (RCNR), University of Tehran, Tehran, Iran
3   Tissue Repair Lab, Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran
,
Mohammad Hossein Nabian
1   Research Center for Neural Repair (RCNR), University of Tehran, Tehran, Iran
2   Department of Orthopedic and Trauma Surgery, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
,
Shayan Abdollah Zadegan
1   Research Center for Neural Repair (RCNR), University of Tehran, Tehran, Iran
3   Tissue Repair Lab, Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran
,
Mohsen Nategh
1   Research Center for Neural Repair (RCNR), University of Tehran, Tehran, Iran
3   Tissue Repair Lab, Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran
,
Reza Erfanian
1   Research Center for Neural Repair (RCNR), University of Tehran, Tehran, Iran
3   Tissue Repair Lab, Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran
,
Ahmad Mohebbi Ashtiani
1   Research Center for Neural Repair (RCNR), University of Tehran, Tehran, Iran
,
Reza Shahryar Kamrani
2   Department of Orthopedic and Trauma Surgery, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
› Author Affiliations
Further Information

Publication History

29 May 2015

15 November 2015

Publication Date:
05 February 2016 (online)

    Permissions and Reprints

Abstract

Background Extraneural scar formation is a challenging problem in nerve repair. Rodent models of scar induction, with their high regenerative capacity, suffer from lack of comparable similarities with human cases. In this study, we attempted to find a reliable and reproducible method of extraneural scarring with a significant impact on the peripheral nerve function.

Methods A total of 60 rats were divided into three scar induction groups: abrasion (with a small piece of compressed steel wool), mincing (with extracorporeal mincing of adductor muscle and a 5-mm wide strip of the anterior border of the biceps femoris), and electrocoagulation (with a bipolar coagulator). Extraneural scarring was evaluated macroscopically and histologically during 8 weeks. The tibial functional index was used for behavioral analysis.

Results Among three different physical methods of scar induction that were applied, electrocoagulation had the most functional impairment (p < 0.001, two-way analysis of variance); whereas mincing produced the most adhesive and intensive scar, morphologically (p < 0.001).

Conclusion We conclude that: (1) the impact of the extraneural scar on the nerve is morphologically and functionally different, based on the method of scarring; (2) to achieve a scar model comparable to the human situation, a method in which the involved nerve is functionally impaired, is preferred over the ones that merely produce a bulky scar.

Keywords

peripheral nerve - sciatic nerve - scar - regeneration - experimental model
 

  • References

  • 1 Ozgenel GY. Effects of hyaluronic acid on peripheral nerve scarring and regeneration in rats. Microsurgery 2003; 23 (6) 575-581
    CrossrefPubMedGoogle Scholar
  • 2 Gaudet AD, Popovich PG, Ramer MS. Wallerian degeneration: gaining perspective on inflammatory events after peripheral nerve injury. J Neuroinflammation 2011; 8: 110
    CrossrefPubMedGoogle Scholar
  • 3 Ilbay K, Etus V, Yildiz K, Ilbay G, Ceylan S. Topical application of mitomycin C prevents epineural scar formation in rats. Neurosurg Rev 2005; 28 (2) 148-153
    CrossrefPubMedGoogle Scholar
  • 4 Varejão AS, Meek MF, Ferreira AJ, Patrício JA, Cabrita AM. Functional evaluation of peripheral nerve regeneration in the rat: walking track analysis. J Neurosci Methods 2001; 108 (1) 1-9
    CrossrefPubMedGoogle Scholar
  • 5 Cheng DS, Rogers J, Wheeler A, Parker R, Teixeira L, Light RW. The effects of intrapleural polyclonal anti-tumor necrosis factor alpha (TNF alpha) Fab fragments on pleurodesis in rabbits. Lung 2000; 178 (1) 19-29
    CrossrefPubMedGoogle Scholar
  • 6 Bilaceroglu S, Guo Y, Hawthorne ML , et al. Oral forms of tetracycline and doxycycline are effective in producing pleurodesis. Chest 2005; 128 (5) 3750-3756
    CrossrefPubMedGoogle Scholar
  • 7 Wachter BG, Leonetti JP, Lee JM, Wurster RD, Young MR. Silver nitrate injury in the rat sciatic nerve: a model of facial nerve injury. Otolaryngol Head Neck Surg 2002; 127 (1) 48-54
    CrossrefPubMedGoogle Scholar
  • 8 Kalender AM, Dogan A, Bakan V, Yildiz H, Gokalp MA, Kalender M. Effect of Zofenopril on regeneration of sciatic nerve crush injury in a rat model. J Brachial Plex Peripher Nerve Inj 2009; 4: 6
    PubMedGoogle Scholar
  • 9 Smit X, van Neck JW, Afoke A, Hovius SE. Reduction of neural adhesions by biodegradable autocrosslinked hyaluronic acid gel after injury of peripheral nerves: an experimental study. J Neurosurg 2004; 101 (4) 648-652
    CrossrefPubMedGoogle Scholar
  • 10 Zuijdendorp HM, Smit X, Blok JH , et al. Significant reduction in neural adhesions after administration of the regenerating agent OTR4120, a synthetic glycosaminoglycan mimetic, after peripheral nerve injury in rats. J Neurosurg 2008; 109 (5) 967-973
    CrossrefPubMedGoogle Scholar
  • 11 Finsterbush A, Porat S, Rousso M, Ashur H. Prevention of peripheral nerve entrapment following extensive soft tissue injury, using silicone cuffing: an experimental study. Clin Orthop Relat Res 1982; (162) 276-281
    PubMedGoogle Scholar
  • 12 O. Zanjani L, Firouzi M, Nabian MH, Nategh M, Rahimi-Movaghar V, S. Kamrani R. Comparison and evaluation of current animal models for perineural scar formation in rat. Iran J Basic Med Sci 2013; 16 (7) 886-890
    PubMedGoogle Scholar
  • 13 Petersen J, Russell L, Andrus K, MacKinnon M, Silver J, Kliot M. Reduction of extraneural scarring by ADCON-T/N after surgical intervention. Neurosurgery 1996; 38 (5) 976-983 , discussion 983–984
    CrossrefPubMedGoogle Scholar
  • 14 Görgülü A, Imer M, Simşek O, Sencer A, Kutlu K, Cobanoğlu S. The effect of aprotinin on extraneural scarring in peripheral nerve surgery: an experimental study. Acta Neurochir (Wien) 1998; 140 (12) 1303-1307
    CrossrefPubMedGoogle Scholar
  • 15 Albayrak BS, Ismailoglu O, Ilbay K , et al. Doxorubicin for prevention of epineurial fibrosis in a rat sciatic nerve model: outcome based on gross postsurgical, histopathological, and ultrastructural findings. J Neurosurg Spine 2010; 12 (3) 327-333
    CrossrefPubMedGoogle Scholar
  • 16 Palatinsky EA, Maier KH, Touhalisky DK, Mock JL, Hingson MT, Coker GT. ADCON-T/N reduces in vivo perineural adhesions in a rat sciatic nerve reoperation model. J Hand Surg [Br] 1997; 22 (3) 331-335
    CrossrefPubMedGoogle Scholar
  • 17 Ikeda K, Yamauchi D, Osamura N, Hagiwara N, Tomita K. Hyaluronic acid prevents peripheral nerve adhesion. Br J Plast Surg 2003; 56 (4) 342-347
    CrossrefPubMedGoogle Scholar
  • 18 Yamamoto M, Endo N, Ito M , et al. Novel polysaccharide-derived hydrogel prevents perineural adhesions in a rat model of sciatic nerve adhesion. J Orthop Res 2010; 28 (3) 284-288
    PubMedGoogle Scholar
  • 19 Ikeda K, Yamauchi D, Tomita K. Preliminary study for prevention of neural adhesion using an absorbable oxidised regenerated cellulose sheet. Hand Surg 2002; 7 (1) 11-14
    CrossrefPubMedGoogle Scholar
  • 20 Ohsumi H, Hirata H, Nagakura T , et al. Enhancement of perineurial repair and inhibition of nerve adhesion by viscous injectable pure alginate sol. Plast Reconstr Surg 2005; 116 (3) 823-830
    CrossrefPubMedGoogle Scholar
  • 21 Ngeow WC, Atkins S, Morgan CR , et al. The effect of Mannose-6-Phosphate on recovery after sciatic nerve repair. Brain Res 2011; 1394: 40-48
    CrossrefPubMedGoogle Scholar
  • 22 Koshima I, Harii K. Experimental study of vascularized nerve grafts: multifactorial analyses of axonal regeneration of nerves transplanted into an acute burn wound. J Hand Surg Am 1985; 10 (1) 64-72
    Google Scholar
  • 23 Ngeow WC. Scar less: a review of methods of scar reduction at sites of peripheral nerve repair. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010; 109 (3) 357-366
    CrossrefPubMedGoogle Scholar
  • 24 Firouzi MS, Firouzi M, Nabian MH , et al. The effects of picric acid (2,4,6-trinitrophenol) and a bite-deterrent chemical (denatonium benzoate) on autotomy in rats after peripheral nerve lesion. Lab Anim (NY) 2015; 44 (4) 141-145
    CrossrefPubMedGoogle Scholar
  • 25 de Medinaceli L, DeRenzo E, Wyatt RJ ; de ML. Rat sciatic functional index data management system with digitized input. Comput Biomed Res 1984; 17 (2) 185-192
    CrossrefPubMedGoogle Scholar
  • 26 Bain JR, Mackinnon SE, Hunter DA. Functional evaluation of complete sciatic, peroneal, and posterior tibial nerve lesions in the rat. Plast Reconstr Surg 1989; 83 (1) 129-138
    CrossrefPubMedGoogle Scholar
  • 27 Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods 2012; 9 (7) 671-675
    CrossrefPubMedGoogle Scholar
  • 28 Mayhew TM. An efficient sampling scheme for estimating fibre number from nerve cross sections: the fractionator. J Anat 1988; 157: 127-134
    PubMedGoogle Scholar
  • 29 Larsen JO. Stereology of nerve cross sections. J Neurosci Methods 1998; 85 (1) 107-118
    CrossrefPubMedGoogle Scholar
  • 30 Gundersen HJ. Stereology of arbitrary particles. A review of unbiased number and size estimators and the presentation of some new ones, in memory of William R. Thompson. J Microsc 1986; 143 (Pt 1) 3-45
    CrossrefPubMedGoogle Scholar
  • 31 Geuna S, Tos P, Battiston B, Guglielmone R. Verification of the two-dimensional disector, a method for the unbiased estimation of density and number of myelinated nerve fibers in peripheral nerves. Ann Anat 2000; 182 (1) 23-34
    CrossrefPubMedGoogle Scholar
  • 32 Brenner MJ, Moradzadeh A, Myckatyn TM , et al. Role of timing in assessment of nerve regeneration. Microsurgery 2008; 28 (4) 265-272
    CrossrefPubMedGoogle Scholar
  • 33 Chen FM, Zhao YM, Jin Y, Shi S. Prospects for translational regenerative medicine. Biotechnol Adv 2012; 30 (3) 658-672
    CrossrefPubMedGoogle Scholar
  • 34 Adanali G, Verdi M, Tuncel A, Erdogan B, Kargi E. Effects of hyaluronic acid-carboxymethylcellulose membrane on extraneural adhesion formation and peripheral nerve regeneration. J Reconstr Microsurg 2003; 19 (1) 29-36
    Article in Thieme ConnectPubMedGoogle Scholar
  • 35 van der Veer WM, Bloemen MC, Ulrich MM , et al. Potential cellular and molecular causes of hypertrophic scar formation. Burns 2009; 35 (1) 15-29
    CrossrefPubMedGoogle Scholar
  • 36 Wang XQ, Kravchuk O, Winterford C, Kimble RM. The correlation of in vivo burn scar contraction with the level of α-smooth muscle actin expression. Burns 2011; 37 (8) 1367-1377
    CrossrefPubMedGoogle Scholar
  • 37 Abe Y, Doi K, Kawai S. An experimental model of peripheral nerve adhesion in rabbits. Br J Plast Surg 2005; 58 (4) 533-540
    CrossrefPubMedGoogle Scholar
  • 38 Muschler GF, Raut VP, Patterson TE, Wenke JC, Hollinger JO. The design and use of animal models for translational research in bone tissue engineering and regenerative medicine. Tissue Eng Part B Rev 2010; 16 (1) 123-145
    PubMedGoogle Scholar