The Effect of Sildenafil on Recuperation from Sciatic Nerve Injury in Rats

The Effect of Sildenafil on Recuperation from Sciatic Nerve Injury in Rats

Background: Severe functional and anatomical defects can be detected after the peripheral nerve injury. Pharmacological approaches are preferred rather than surgical treatment in the treatment of nerve injuries. Aims: The aim of this study is to perform histopathological, functional and bone densitometry examinations of the effects of sildenafil on nerve regeneration in a rat model of peripheral nerve crush injury. Study Design: Animal experiment. Methods: The study included a total of thirty adult Sprague-Dawley rats that were divided into three groups of ten rats each. In all rats, a crush injury was created by clamping the right sciatic nerve for one minute. One day before the procedure, rats in group 1 were started on a 28-day treatment consisting of a daily dose of 20 mg/kg body weight sildenafil citrate given orally via a nasogastric tube, while the rats in group 2 were started on an every-other-day dose of 10 mg/kg body weight sildenafil citrate. Rats from group 3 were not administered any drugs. Forty-two days after the nerve damage was created, functional and histopathological examination of both sciatic nerves and bone densitometric evaluation of the extremities were conducted. Results: During the rotarod test, rats from group 3 spent the least amount of time on the rod compared to the drug treatment groups at speeds of 20 rpm, 30 rpm and 40 rpm. In addition, the duration for which each animal could stay on the rod throughout the accelerod test significantly reduced in rats from group 3 compared to rats from groups 1 and 2 in the 4-min test. For the hot-plate latency time, there were no differences among the groups in either the basal level or after sciatic nerve injury. Moreover, there was no significant difference between the groups in terms of the static sciatic index (SSI) on the 42nd day (p=0.147). The amplitude was better evaluated in group 1 compared to the other two groups (p

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  • Avci G, Akan M, Yildirim S, Akoz T. Sinir onarimi ve gref- tleme. T Klin J Med Sci 2002;22:428-37.
  • Rummler L, Gupta R. Peripheral nerve repair: a Review. Curr Opin Orthop 2004;15:215-9. [CrossRef]
  • Erbayraktar S, Grasso G, Sfacteria A, Xie QW, Coleman T, Kreilgaard M, et al. Asialoerythropoietin is a nonerythropoi- etic cytokine with broad neuroprotective activity in vivo. P Natl Acad Sci USA 2003;100:6741-6. [CrossRef]
  • Korkmaz HA, Maltepe F, Erbayraktar S, Yilmaz O, Guray M, Canda MS, et al. Antinociceptive and neurotoxicologic screening of chronic intrathecal administration of ketorolac tromethamine in the rat. Anesthesia Analg 2004;98:148-52. [CrossRef]
  • Seddon HJ, Medawar PB, Smith H. Rate of regeneration of pe- ripheral nerves in man. J Physiol 1943;102:191-215. [CrossRef]
  • Varejao AS, Meek MF, Ferreira AJ, Patricio JA, Cabrita AM. Functional evaluation of peripheral nerve regenera- tion in the rat: walking track analysis. J Neurosci Methods 2001;108:1-9. [CrossRef]
  • Das S, Maulik N, Das DK, Kadowitz PJ, Bivalacqua TJ. Car- dioprotection with sildenafil, a selective inhibitor of cyclic 3',5'-monophosphate-specific phosphodiesterase 5. Drugs Exp Clin Res 2002;28:213-9.
  • Salloum F, Yin C, Xi L, Kukreja RC. Sildenafil induces de- layed preconditioning through inducible nitric oxide synthase- dependent pathway in mouse heart. Circ Res 2003;92:595-7. [CrossRef]
  • Bandera BC, Pham T, Hill-Pryor C, Bah-Sow M, Franco N, Prasad BM, et al. Role of Growth Factors in Improved Skin Flap Viability Caused by Phosphodiesterase-5 Inhibitor. Am Surg 2010;76:614-7.
  • Mulhall JP, Muller A, Donohue JF, Mullerad M, Kobylarz K, Paduch DA, et al. The functional and structural consequences of cavernous nerve injury are ameliorated by sildenafil ci- trate. J Sex Med 2008;5:1126-36. [CrossRef]
  • Yucel A, Aydogan MS, Parlakpinar H, Erdogan MA, Kurt A, Ucar M, et al. Effects of propofol and dexmedetomidine on motor coordination and analgesia: A comparative analysis. Int J Clin Pharmacol Ther 2012;50:678-82. [CrossRef]
  • Baptista AF, Gomes JR, Oliveira JT, Santos SM, Vannier- Santos MA, Martinez AM. A new approach to assess func- tion after sciatic nerve lesion in the Mouse adaptation of the sciatic static index. J Neurosci Methods 2007;161:259-64. [CrossRef]
  • Ali Erdogan M, Polat A, Yucel A, Aydogan MS, Parlakpinar H, Tekin S, et al. Effects of perineural administration of dex- medetomidine in combination with levobupivacaine in a rat sciatic nerve block. Curr Ther Res Clin Exp 2013;74:74-8. [CrossRef]
  • Arslan E, Milcan A, Unal S, Demirkan F, Polat A, Bagdatoglu O, et al. The effects of carnitine on distally-burned dorsal skin flap: an experimental study in rats. Burns 2003;29:221- 7. [CrossRef]
  • Bagdatoglu C, Saray A, Surucu HS, Ozturk H, Tamer L. Ef- fect of trapidil in ischemia/reperfusion injury of peripheral nerves. Neurosurgery 2002;51:212-9; discussion 219-20. [CrossRef]
  • Zochodne DW, Ho LT. Endoneurial microenvironment and acute nerve crush injury in the rat sciatic nerve. Brain Res 1990;535:43-8. [CrossRef]
  • Sunderland S. The anatomy and physiology of nerve injury. Muscle Nerve 1990;13:771-84. [CrossRef]
  • Seddon H. Three types of nerve injury. Brain 1943;66:237- 88. [CrossRef]
  • Al-Bishri A, Dahlin L, Sunzel B, Rozenquist J. Systemic be- tamethasone accelerates functional recovery after a crush in- jury to rat sciatic nerve. J Oral Maxillofac Surg 2005;63:973- 7. [CrossRef]
  • Ditor DS, John SM, Roy J, Marx JC, Kittmer C, Weaver LC. Effects of polyethylene glycol and magnesium sul- fate administration on clinically relevant neurological out- comes after spinal cord injury in the rat. J Neurosci Res 2007;85:1458-67. [CrossRef]
  • Le Prell CG, Hughes LF, Miller JM. Free radical scavengers vitamins A, C, and E plus magnesium reduce noise trauma. Free Radic Biol Med 2007;42:1454-63. [CrossRef]
  • Lee M, Doolabh VB, Mackinnon SE, Jost S. FK506 promotes functional recovery in crushed rat sciatic nerve. Muscle Nerve 2000;23:633-40. [CrossRef]
  • Subbanna PK, Prasanna CG, Gunale BK, Tyagi MG. Acetyl salicylic acid augments functional recovery following sci- atic nerve crush in mice. J Brachial Plex Peripher Nerve Inj 2007;2:3.
  • Wilson AD, Hart A, Brannstrom T, Wiberg M, Terenghi G. Delayed acetyl-L-carnitine administration and its effect on sensory neuronal rescue after peripheral nerve injury. J Plast Reconstr Aesthet Surg 2007;60:114-8. [CrossRef]
  • Gordon T, Sulaiman O, Boyd JG. Experimental strategies to promote functional recovery after peripheral nerve injuries. J Peripher Nerv Syst 2003;8:236-50. [CrossRef]
  • Stoll G, Muller HW. Nerve injury, axonal degeneration and neural regeneration: basic insights. Brain Pathol 1999;9:313- 25. [CrossRef]
  • Gudemez E, Ozer K, Cunningham B, Siemionow K, Browne E, Siemionow M. Dehydroepiandrosterone as an enhancer of functional recovery following crush injury to rat sciatic nerve. Microsurgery 2002;22:234-41. [CrossRef]
  • Oliveira EF, Mazzer N, Barbieri CH, Selli M. Correlation be- tween functional index and morphometry to evaluate recovery of the rat sciatic nerve following crush injury: Experimental study. J Reconstr Microsurg 2001;17:69-75. [CrossRef]
  • Rempel D, Dahlin L, Lundborg G. Pathophysiology of nerve compression syndromes: Response of peripheral nerves to loading. J Bone Joint Surg Am 1999;81A:1600-10.
  • Johnson EO, Zoubos AB, Soucacos PN. Regeneration and re- pair of peripheral nerves. Injury 2005;36:S24-9. [CrossRef]
  • Galtrey CM, Fawcett GJW. Characterization of tests of func- tional recovery after median and ulnar nerve injury and re- pair in the rat forelimb. J Peripher Nerv Syst 2007;12:11-27. [CrossRef]
  • Novak CB, Mackinnon SE. Nerve injury in repetitive motion disorders. Clin Orthop Relat Res 1998;10-20. [CrossRef]
  • Zuo YX, Perkins NM, Tracey DJ, Geczy CL. Inflammation and hyperalgesia induced by nerve injury in the rat: a key role of mast cells. Pain 2003;105:467-79. [CrossRef]
  • Yang J, Li XH, Al-Lamki RS,Wu C, Weiss A, Berk J, et al. Sildenafil Potentiates Bone Morphogenetic Protein Signal- ing in Pulmonary Arterial Smooth Muscle Cells and in Ex- perimental Pulmonary Hypertension. Arterioscl Throm Vas 2013;33:34-42. [CrossRef]
  • Yaman F, Atilgan S, Gunes N, Agacayak S, Günay A, Ucan MC, et al. Phosphodiesterase-5 inhibitors may facilitate bone defect recovery. Eur Rev Med Pharmacol Sci 2011;15:1301- 5.
  • Histing T, Marciniak K, Scheuer C, Garcia P, Holstein JH, Klein M, et al. Sildenafil Accelerates Fracture Healing in Mice. J Orthop Res 2011;29:867-73. [CrossRef]
  • Sun L, Pan JP, Peng YZ, Wu Y, Li J, Liu X, et al. Anabolic steroids reduce spinal cord injury-related bone loss in rats associated with increased Wnt signaling. J Spinal Cord Med 2013;36:616-22. [CrossRef]
  • Jiang SD, Jiang LS, Dai LY. Spinal cord injury causes more damage to bone mass, bone structure, biomechanical proper- ties and bone metabolism than sciatic neurectomy in young rats. Osteoporos Int 2006;17:1552-61. [CrossRef]
  • Suyama H, Moriwaki K, Niida S, Maehara Y, Kawamoto M, Yuge O. Osteoporosis following chronic constriction injury of sciatic nerve in rats. J Bone Miner Metab 2002;20:91-7. [CrossRef]
  • Cardozo CP, Qin WP, Peng YZ, Liu X, Wu Y, Pan J, et al. Nandro- lone slows hindlimb bone loss in a rat model of bone loss due to denervation. Ann Ny Acad Sci 2010;1192:303-6.[CrossRef]
Balkan Medical Journal-Cover
  • ISSN: 2146-3123
  • Başlangıç: 2015
  • Yayıncı: Erkan Mor
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