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J Reconstr Microsurg 2017; 33(05): 352-357
DOI: 10.1055/s-0037-1598619
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Muscle Response to Complete Peripheral Nerve Injury: Changes of Acetylcholine Receptor and Creatine Kinase Activity over Time

Shimon Rochkind
1   Division of Peripheral Nerve Reconstruction, Department of Neurosurgery, Tel Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel
2   Faculty of Life Science, Bar-Ilan University, Ramat-Gan, Israel
,
Asher Shainberg
2   Faculty of Life Science, Bar-Ilan University, Ramat-Gan, Israel
› Author Affiliations
Further Information

Publication History

03 September 2016

26 December 2016

Publication Date:
20 February 2017 (online)

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Abstract

Background This study was designed to assess the changes of acetylcholine receptor (AChR) and creatine kinase (CK) levels, which are important biochemical markers for muscle viability in cases of long-term muscle denervation. Scientists and peripheral nerve surgeons may find these data important regarding maximal range of muscle viability applicable for timing of effective peripheral nerve reconstructive surgery.

Methods The study was conducted on 48 rats (96 gastrocnemius muscles), whose right legs were denervated by removing a 10-mm segment of sciatic nerve, while their left legs remained intact. Under general anesthesia, the rats were euthanized at seven points in time, on days 7, 14, 21, 30, 60, 120, and 210. In both legs, AChR was quantified by 125I-α-bungarotoxin, whereas CK activity was measured using a spectrophotometric method.

Results CK levels in the denervated limb reached a minimal level of 34% on day 30 in comparison to the intact limb and remained at this level up to 210 days after operation. AChR levels in the denervated limb reached a minimal level of 38% on day 120 in comparison to the intact limb and remained at this level up to 210 days after operation.

Conclusion The present study shows that AChR and CK levels in rat denervated muscles remain constant at about third of its intact condition for a period of at least a third of rat's lifetime postinjury.

Keywords

muscle denervation - acetylcholine receptors - creatine kinase
 

  • References

  • 1 Gutmann E, Zelena J. Morphological changes in the denervated muscle. In: Gutmann E, , ed. The Denervated Muscle. Prague, Czech Republic: Publishing House of the Czechoslovak Academy of Sciences; 1962: 57-102
    CrossrefGoogle Scholar
  • 2 Anzil AP, Wernig A. Muscle fibre loss and reinnervation after long-term denervation. J Neurocytol 1989; 18 (6) 833-845
    CrossrefPubMedGoogle Scholar
  • 3 Borisov AB, Carlson BM. Cell death in denervated skeletal muscle is distinct from classical apoptosis. Anat Rec 2000; 258 (3) 305-318
    CrossrefPubMedGoogle Scholar
  • 4 Schmalbruch H, Lewis DM. Dynamics of nuclei of muscle fibers and connective tissue cells in normal and denervated rat muscles. Muscle Nerve 2000; 23 (4) 617-626
    CrossrefPubMedGoogle Scholar
  • 5 Bolesta MJ, Garrett Jr WE, Ribbeck BM, Glisson RR, Seaber AV, Goldner JL. Immediate and delayed neurorrhaphy in a rabbit model: a functional, histologic, and biochemical comparison. J Hand Surg Am 1988; 13 (3) 352-357
    CrossrefPubMedGoogle Scholar
  • 6 Carlson BM, Faulkner JA. Reinnervation of long-term denervated rat muscle freely grafted into an innervated limb. Exp Neurol 1988; 102 (1) 50-56
    CrossrefPubMedGoogle Scholar
  • 7 Aydin MA, Mackinnon SE, Gu XM, Kobayashi J, Kuzon Jr WM. Force deficits in skeletal muscle after delayed reinnervation. Plast Reconstr Surg 2004; 113 (6) 1712-1718
    CrossrefPubMedGoogle Scholar
  • 8 Fu SY, Gordon T. Contributing factors to poor functional recovery after delayed nerve repair: prolonged denervation. J Neurosci 1995; 15 (5 Pt 2): 3886-3895
    CrossrefPubMedGoogle Scholar
  • 9 MacKinnon SE, Dellon AL. Surgery of the Peripheral Nerve. New York, NY: Thieme Medical Publishers; 1988
    Google Scholar
  • 10 Belzberg AJ, Dorsi MJ, Storm PB, Moriarity JL. Surgical repair of brachial plexus injury: a multinational survey of experienced peripheral nerve surgeons. J Neurosurg 2004; 101 (3) 365-376
    CrossrefPubMedGoogle Scholar
  • 11 Midha R. Mechanism and pathology of injury. In: Kline DG, Hudson AR, , eds. Nerve Injury. St. Louis, MO: Saunders Elsevier; 2008: 23-42
    Google Scholar
  • 12 Spinner RJ. Operative care and techniques. In: Kline DG, Hudson AR, , eds. Nerve Injury. Saunders Elsevier; 2008: 87-105
    Google Scholar
  • 13 Washabaugh CH, Ontell MP, Kant JA , et al. Effect of chronic denervation and denervation-reinnervation on cytoplasmic creatine kinase transcript accumulation. J Neurobiol 2001; 47 (3) 194-206
    CrossrefPubMedGoogle Scholar
  • 14 Lu D-X, Huang S-K, Carlson BM. Electron microscopic study of long-term denervated rat skeletal muscle. Anat Rec 1997; 248 (3) 355-365
    CrossrefPubMedGoogle Scholar
  • 15 Vrbova FG, Gordon T, Jones R. Nerve-Muscle Interactions. London, UK: Chapman and Hall; 1995
    Google Scholar
  • 16 Kline DG, Hackett ER. Reappraisal of timing for exploration of civilian peripheral nerve injuries. Surgery 1975; 78 (1) 54-65
    PubMedGoogle Scholar
  • 17 Narakas A. Surgical treatment of traction injuries of the brachial plexus. Clin Orthop Relat Res 1978; 133 (133) 71-90
    PubMedGoogle Scholar
  • 18 Rochkind S, Alon M. Microsurgical management of old injuries of the peripheral nerve and brachial plexus. J Reconstr Microsurg 2000; 16 (7) 541-546
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Rochkind S, Filmar G, Kluger Y, Alon M. Microsurgical management of penetrating peripheral nerve injuries: pre, intra- and postoperative analysis and results. Acta Neurochir Suppl (Wien) 2007; 100: 21-24
    PubMedGoogle Scholar
  • 20 Wallimann T, Wyss M, Brdiczka D, Nicolay K, Eppenberger HM. Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the ‘phosphocreatine circuit’ for cellular energy homeostasis. Biochem J 1992; 281 (Pt 1): 21-40
    CrossrefPubMedGoogle Scholar
  • 21 Goldspink DF. The effects of denervation on protein turnover of rat skeletal muscle. Biochem J 1976; 156 (1) 71-80
    CrossrefPubMedGoogle Scholar
  • 22 Lomo T, Westgaard RH. Further studies on the control of ACh sensitivity by muscle activity in the rat. J Physiol 1975; 252 (3) 603-626
    CrossrefPubMedGoogle Scholar
  • 23 Guzzini M, Raffa S, Geuna S , et al. Denervation-related changes in acetylcholine receptor density and distribution in the rat flexor digitorum sublimis muscle. Ital J Anat Embryol 2008; 113 (4) 209-216
    PubMedGoogle Scholar
  • 24 Lapalombella R, Kern H, Adami N , et al. Persistence of regenerative myogenesis in spite of down-regulation of activity-dependent genes in long-term denervated rat muscle. Neurol Res 2008; 30 (2) 197-206
    CrossrefPubMedGoogle Scholar
  • 25 Willand MP, Rosa E, Michalski B , et al. Electrical muscle stimulation elevates intramuscular BDNF and GDNF mRNA following peripheral nerve injury and repair in rats. Neuroscience 2016; 334: 93-104
    CrossrefPubMedGoogle Scholar
  • 26 Artioli GG, De Oliveira Silvestre JG, Guilherme JP , et al. Embryonic stem cells improve skeletal muscle recovery after extreme atrophy in mice. Muscle Nerve 2015; 51 (3) 346-352
    CrossrefPubMedGoogle Scholar
  • 27 Rochkind S, Geuna S, Shainberg A. Phototherapy and nerve injury: focus on muscle response. Int Rev Neurobiol 2013; 109: 99-109
    PubMedGoogle Scholar
  • 28 Borisov AB, Dedkov EI, Carlson BM. Interrelations of myogenic response, progressive atrophy of muscle fibers, and cell death in denervated skeletal muscle. Anat Rec 2001; 264 (2) 203-218
    CrossrefPubMedGoogle Scholar
  • 29 Dow DE, Cederna PS, Hassett CA, Kostrominova TY, Faulkner JA, Dennis RG. Number of contractions to maintain mass and force of a denervated rat muscle. Muscle Nerve 2004; 30 (1) 77-86
    CrossrefPubMedGoogle Scholar
  • 30 Rochkind S, Geuna S, Shainberg A. Chapter 25: Phototherapy in peripheral nerve injury: effects on muscle preservation and nerve regeneration. Int Rev Neurobiol 2009; 87: 445-464
    PubMedGoogle Scholar
  • 31 Schmalbruch H. Growth and denervation response of skeletal muscle fibers of newborn rats. Muscle Nerve 1990; 13 (5) 421-432
    CrossrefPubMedGoogle Scholar
  • 32 Trachtenberg JT. Fiber apoptosis in developing rat muscles is regulated by activity, neuregulin. Dev Biol 1998; 196 (2) 193-203
    CrossrefPubMedGoogle Scholar
  • 33 Almon RR, Andrew CG, Appel SH. Acetylcholine receptor in normal and denervated slow and fast muscle. Biochemistry 1974; 13 (27) 5522-5528
    CrossrefPubMedGoogle Scholar
  • 34 Chin H, Almon RR. Fiber-type effects of castration on the cholinergic receptor population in skeletal muscle. J Pharmacol Exp Ther 1980; 212 (3) 553-559
    PubMedGoogle Scholar
  • 35 Oliver IT. A spectrophotometric method for the determination of creatine phosphokinase and myokinase. Biochem J 1955; 61 (1) 116-122
    CrossrefPubMedGoogle Scholar
  • 36 Shainberg A, Yagil G, Yaffe D. Alterations of enzymatic activities during muscle differentiation in vitro. Dev Biol 1971; 25 (1) 1-29
    CrossrefPubMedGoogle Scholar
  • 37 Battiston B, Geuna S, Ferrero M, Tos P. Nerve repair by means of tubulization: literature review and personal clinical experience comparing biological and synthetic conduits for sensory nerve repair. Microsurgery 2005; 25 (4) 258-267
    CrossrefPubMedGoogle Scholar
  • 38 Wada K, Katsuta S, Soya H. Formation process and fate of the nuclear chain after injury in regenerated myofiber. Anat Rec (Hoboken) 2008; 291 (1) 122-128
    CrossrefPubMedGoogle Scholar
  • 39 Yang B, Jiang JH, Zhou YC, Zhang Y, Li ST. Denervation stage differentially influences resistance to neuromuscular blockers in rat gastrocnemius. J Surg Res 2013; 180 (2) 266-273
    CrossrefPubMedGoogle Scholar
  • 40 Irintchev A, Draguhn A, Wernig A. Reinnervation and recovery of mouse soleus muscle after long-term denervation. Neuroscience 1990; 39 (1) 231-243
    CrossrefPubMedGoogle Scholar
  • 41 Kloosterboer HJ, van Faassen H, Stoker-de Vries SA, Hommes FA. Effect of cyclic nucleotides on weight of gastrocnemius and creatine kinase activity after denervation of muscle in young rats. Biol Neonate 1979; 36 (03/04): 160-167
    CrossrefPubMedGoogle Scholar
  • 42 Sadeh M, Stern LZ, Czyzewski K, Finley PR, Russell DH. Increased activities of MB and BB isozymes of creatine kinase in denervated neonatal and adult rat muscle. Exp Neurol 1984; 83 (3) 640-645
    CrossrefPubMedGoogle Scholar
  • 43 Sunderland S, Ray LJ. Denervation changes in mammalian striated muscle. J Neurol Neurosurg Psychiatry 1950; 13 (3) 159-177
    CrossrefPubMedGoogle Scholar
  • 44 Dedkov EI, Kostrominova TY, Borisov AB, Carlson BM. Reparative myogenesis in long-term denervated skeletal muscles of adult rats results in a reduction of the satellite cell population. Anat Rec 2001; 263 (2) 139-154
    CrossrefPubMedGoogle Scholar
  • 45 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