Contribution of the Distal Nerve Sheath to Nerve and Muscle Preservation Following Denervation and Sensory Protection

ABSTRACT

The goal of this study was to determine the contribution of the distal nerve sheath to sensory protection. Following tibial nerve transection, rats were assigned to one of the following groups: (1) saphenous-to-tibial nerve neurorrhaphy; (2) saphenous-to-gastrocnemius neurotization; (3) unprotected controls (tibial nerve transection); or (4) immediate common peroneal-to-tibial nerve neurorrhaphy. After a 6-month denervation period and motor reinnervation, ultrastructural, histologic, and morphometric analyses were performed on the distal tibial nerve and gastrocnemius muscle cross-sections. Sensory axons neurotized to muscle maintain existing muscle integrity, as demonstrated by less fibrosis, collagenization, and fat deposition, more than unprotected muscle, and preserve the distribution pattern of fast twitch fibers. However, neurorrhaphy of the sensory nerve to the distal tibial nerve (involving the distal nerve sheath) improves existing endoneurial sheath structure, demonstrated by reduced collagen, and enhances regeneration, shown by improved axon-to-Schwann cell coupling and increased axon area. The authors conclude that sensory protection of muscle does not require the distal nerve sheath, but that preservation of the distal sheath may contribute to enhanced nerve regeneration.

KEYWORDS

Sensory protection - denervation

REFERENCES

• 1 Cormack D H. Ham's Histology, 9th edition. Philadelphia J.B. Lippincott Company; 1987
• 2 Morris J H, Hudson A R, Weddell G A. A study of degeneration and regeneration in the divided rat sciatic nerve based on electron microscopy. II. The development of the “regenerating unit”.  Z Zellforschung. 1972;  124 103-130
• 3 Fu S Y, Gordon T. Contributing factors to poor functional recovery after delayed nerve repair: prolonged denervation.  J Neurosci. 1995;  15 3886-3895
• 4 Fu S Y, Gordon T. Contributing factors to poor functional recovery after delayed nerve repair: prolonged axotomy.  J Neurosci. 1995;  15 3876-3885
• 5 Waller A. Experiments on the section of the glossopharyngeal and hypoglossal nerves of the frog and observations of the alterations produced thereby in the structure of their primitive fibres.  Philosophical Transactions of the Royal Society of London. 1850;  140 423-429
• 6 Reynolds M L, Woolf C J. Terminal Schwann cells elaborate extensive processes following denervation of the motor endplate.  J Neurocytol. 1992;  21 50-66
• 7 Helgren M E, Squinto S P, Davis H L et al.. Trophic effect of ciliary neurotrophic factor on denervated skeletal muscle.  Cell. 1994;  76 493-504
• 8 Irintchev A, Draguhn A, Wernig A. Reinnervation and recovery of mouse soleus muscle after long-term denervation.  Neurosci. 1990;  39 231-243
• 9 Sunderland S. Factors influencing the development of severity of the changes in denervated muscle. In: Nerve Injuries and their Repair NY; Churchill Livingstone 1991
• 10 Weiss P, Edds J R. Sensory-motor nerve crosses in the rat.  J Neurophysiol. 1945;  8 173-193
• 11 Gutmann E. The reinnervation of muscle by sensory nerve fibers.  J Anatomy. 1945;  79 1-8
• 12 Dautel G, Da Silva J B, Floquet J, Merle M. Etude experimentale des effets trophiques de la reinnervation des lambeaux musculaires pedicules.  Chirurgie. 1992;  118 122-130
• 13 Karpati G, Carpenter S, Pena S. Tracer and marker techniques in the microscopic study of skeletal muscles.  Methods Achiev Exp Pathol. 1981;  10 101-137
• 14 Ebert D, Terzis J K. Denervated muscle preservation by sensory protection: a new animal model. Presented at: the 44th Annual Meeting of the Plastic Surgery Research Council Pittsburgh; 1999
• 15 Papakonstantinou K, Kamin E, Terzis J K. Muscle preservation by prolonged sensory protection.  J Reconstr Microsurg. 2002;  18 173-182
• 16 Zhang F, Lineaweaver W C, Ustuner T et al.. Comparison of muscle mass preservation in denervated muscle and transplanted muscle flaps after motor and sensory reinnervation and neurotization.  Plast Reconstr Surg. 1997;  99 803-814
• 17 Wang H, Gu Y, Xu J, Shen L, Li J. Comparative study of different surgical procedures using sensory nerves or neurons for delaying atrophy of denervated skeletal muscle.  J Hand Surg. 2001;  26A 326-331
• 18 Ochi M, Kwong W H, Kimori K, Chow S P, Ikuta Y. Reinnervation of denervated skeletal muscles by grafted dorsal root ganglion.  Exp Neurol. 1992;  118 291-301
• 19 Ochi M, Kwong W H, Kimori K, Takemoto S, Chow S P, Ikuta Y. Delay of the denervation process in skeletal muscle by sensory ganglion graft and its clinical application.  Plast Reconstr Surg. 1996;  97 577-586
• 20 Hynes N M, Bain J R, Thoma A, Veltri K, Maguire J A. Preservation of denervated muscle by sensory protection in rats.  J Reconstr Microsurg. 1997;  13 337-343
• 21 Bain J R, Veltri K L, Chamberlain D, Fahnestock M. Improved functional recovery of denervated skeletal muscle after temporary sensory nerve innervation.  Neurosci. 2001;  103 503-510
• 22 Carr M M, Best T J, Mackinnon S E, Evans P J. Strain differences in autotomy in rats undergoing sciatic nerve transection or repair.  Ann Plast Surg. 1992;  28 538-544
• 23 Harsh C, Archibald S J, Madison R D. Double-labelling of saphenous nerve neuron pools: a model for determining the accuracy of axon regeneration at the single neuron level.  J Neurosci Methods. 1991;  39 123-150
• 24 Brunelli G. Direct neurotization of severely damaged muscles.  J Hand Surg. 1982;  7 572-579
• 25 Kobayashi J, Mackinnon S E, Watanabe O et al.. The effect of duration of muscle denervation on functional recovery in the rat model.  Muscle Nerve. 1997;  20 858-866
• 26 David S, Aguayo A J. Axonal regeneration after crush injury of rat central nervous system fibers innervating peripheral nerve grafts.  J Neurocytol. 1985;  14 1-12
• 27 Kroeber M W, Diao E, Hida S I, Liebenberg E. Peripheral nerve lengthening by controlled isolated distraction: a new animal model.  J Orthopaedic Res. 2001;  19 70-77
• 28 Ghalib N, Houst'Ava L, Haninec P, Dubov P. Morphometric analysis of early regeneration of motor axons through motor and cutaneous nerve grafts.  Ann Anatomy. 2001;  183 363-368
• 29 Loeb G E, Gans C. Anatomical Techniques. Chicago; The University of Chicago Press 1986: 334
• 30 Jenq C B, Coggeshall R E. Numbers of regenerating axons in parent and tributary peripheral nerves in the rat.  Brain Res. 1985;  326 27-40
• 31 Weiss L, Greep R O. Histology, 4th ed. Toronto; McGraw-Hill Book Company 1977
• 32 Nitz A J, Matulionis D H. Ultrastructural changes in rat peripheral nerve following pneumatic tourniquet compression.  J Neurosurg. 1982;  57 660-666
• 33 Grinspan J B, Marchionni M A, Reeves M, Coulaloglou M, Scherer S S. Axonal interactions regulate Schwann cell apoptosis in developing peripheral nerve: neuregulin receptors and the role of neuregulins.  J Neurosci. 1996;  16 6107-6118
• 34 Bradley J L, Abernethy D A, King RH M, Muddle J R, Thomas P K. Neural architecture in transected rabbit sciatic nerve after prolonged nonreinnervation.  J Anat. 1998;  192 529-538
• 35 Dubovicz V. Muscle Biopsy: A Practical Approach, 2nd ed. London; Balliere Tindall 1985
• 36 Daemen M A, Kurvers H A, Bullens P H et al.. Motor denervation induces altered muscle fiber type densities and atrophy in a rat model of neurotrophic pain.  Neurosci Lett. 1998;  247 204-208
• 37 Karpati G, Engel W K. Correlative histochemical study of skeletal muscle after suprasegmental denervation, peripheral nerve section and skeletal fixation.  Neurology. 1968;  18 681-692
• 38 Syroid D E, Maycox P R, Burrola P G et al.. Cell death in the Schwann cell lineage and its regulation by neuregulin.  Proc Natl Acad Sci USA. 1996;  93 9229-9234
• 39 Schmalbruch H. Fiber composition of the rat sciatic nerve.  Anat Rec. 1986;  215 71-81
• 40 Jessen K R, Mirsky R. Schwann cells and their precursors emerge as major regulators of nerve development.  Trends Neurosci. 1999;  22 402-410
• 41 De Waegh S M, Lee V M, Brady S T. Local modulation of neurofilament phosphorylation, axonal calibre, and slow axonal transport by myelinating Schwann cells.  Cell. 1992;  68 451-463
• 42 Black J A, Kocsis J D, Waxman S G. Ion channel organization of the myelinated fiber.  Trends Neurosci. 1990;  13 48-54
• 43 Gutmann E, Young J Z. The reinnervation of muscle after various periods of atrophy.  J Anatomy. 1944;  78 15-44
• 44 Gutmann E. Effect of delay of innervation on recovery of muscle after nerve lesions.  J Neurophysiol. 1948;  11 279-294
• 45 Savolainen J, Myllyla V, Myllyla R et al.. Effects of denervation and immobilization on collagen synthesis in rat skeletal muscle and tendon.  Am J Physiol. 1988;  254 R897-R902
• 46 Engel W K. The essentiality of histo- and cytochemical studies of skeletal muscle in the investigation of neuromuscular disease.  Neurology. 1962;  12 778-794
• 47 Lexell J, Downham D, Sjostram M. Distribution of different fiber types in human skeletal muscles. A statistical and computational model for the study of fiber type grouping and early diagnosis of skeletal muscle fiber denervation and reinnervation.  J Neurol Sci. 1983;  61 301-314
• 48 Lexell J, Downham D, Sjostrom M. Distribution of different fiber types in human skeletal muscles. Fiber type arrangement in m. vastus lateralis from three groups of healthy men between 15 and 83 years.  J Neurol Sci. 1986;  72 211-222
• 49 Lexell J, Wilson C, Downham D. Detection of fiber type grouping: further improvements to the enclosed fiber method.  Muscle Nerve. 1989;  12 1024-1026
• 50 Lexell J, Downham D Y. The occurrence of fiber-type grouping in healthy human muscle: a quantitative study of cross-sections of whole vastus lateralis from men between 15 and 83 years.  Acta Neuropathol (Berl). 1991;  81 377-381
• 51 Zhang Z, Soucacos P N, Beris A E, Bo J, Ioachim E, Johnson E O. Long-term evaluation of rat peripheral nerve repair with end-to-side neurorrhaphy.  J Reconstr Microsurg. 2000;  16 303-311
• 52 Griesbeck O, Parsadanian A Sh, Sendtner M, Thoenen H. Expression of neurotrophins in skeletal muscle: quantitative comparison and significance for motoneuron survival and maintenance of function.  J Neurosci Res. 1995;  42 21-33
• 53 James R, Tonra J R, Curtis R et al.. Axotomy upregulates the anterograde transport and expression of brain derived neurotrophic factor in sensory neurons.  J Neurosci. 1998;  18 4371-4383
• 54 Michael G J, Averill S, Nitkunan A et al.. Nerve growth factor increases brain derived neurotrophic factor selectively in TrkA expressing dorsal root ganglion cells and in their central terminations within the spinal cord.  J Neurosci. 1997;  17 8476-8490
• 55 Falempin M, Ternaux J P, Palouzier B, Chamoin M C. Presence of cholinergic neurons in the vagal afferent system: involvement in a heterogenous reinnervation.  J Auton Nerv Syst. 1989;  28 243-250