Behavioral recovery and spinal motoneuron remodeling after polyethylene glycol fusion repair of singly cut and ablated sciatic nerves

English version

Autoři: Cameron L. Ghergherehchi ^aff001; Emily A. Hibbard ^aff002; Michelle Mikesh ^aff003; George D. Bittner ^aff003; Dale R. Sengelaub ^aff002
Působiště autorů: Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, United States of America ^aff001; Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana, United States of America ^aff002; Department of Neuroscience, University of Texas at Austin, Austin, Texas, United States of America ^aff003
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0223443

Souhrn

Polyethylene glycol repair (PEG-fusion) of severed sciatic axons restores their axoplasmic and membrane continuity, prevents Wallerian degeneration, maintains muscle fiber innervation, and greatly improves recovery of voluntary behaviors. We examined alterations in spinal connectivity and motoneuron dendritic morphology as one potential mechanism for improved behavioral function after PEG-fusion. At 2–112 days after a single-cut or allograft PEG-fusion repair of transected or ablated sciatic nerves, the number, size, location, and morphology of motoneurons projecting to the tibialis anterior muscle were assessed by retrograde labeling. For both lesion types, labeled motoneurons were found in the appropriate original spinal segment, but also in inappropriate segments, indicating mis-pairings of proximal-distal segments of PEG-fused motor axons. Although the number and somal size of motoneurons was unaffected, dendritic distributions were altered, indicating that PEG-fusion preserves spinal motoneurons but reorganizes their connectivity. This spinal reorganization may contribute to the remarkable behavioral recovery seen after PEG-fusion repair.

Klíčová slova:

Nerve fibers – Nerves – Neuronal dendrites – Soleus muscles – Axons – Sciatic nerves – Muscle fibers – Muscle electrophysiology

Zdroje

1. Brushart TM. Nerve repair. New York: Oxford University Press; 2011.

2. Vanden Noven S, Wallace N, Muccio D, Turtz A, Pinter MJ. Adult spinal motoneurons remain viable despite prolonged absence of functional synaptic contact with muscle. Exp Neurol. 1993; 123: 147–156. doi: 10.1006/exnr.1993.1147 8405274

3. Wu CW, Kaas JH. Spinal cord atrophy and reorganization of motoneuron connections following long-standing limb loss in primates. Neuron. 2000; 28: 967–978. doi: 10.1016/s0896-6273(00)00167-7 11163280

4. Ma J, Novikov LN, Wiberg M, Kellerth J-O. Delayed loss of spinal motoneurons after peripheral nerve injury in adult rats: a quantitative morphological study. Exp Brain Res. 2002; 139: 216–223.

5. Grafstein B, McQuarrie EI. Role of the nerve cell body in axonal regeneration. In: Cotman CW, editor. Neuronal plasticity, New York: Raven Press; 1978. pp. 155–195.

6. Titmus MJ, Faber DS. Axotomy-induced alterations in the electrophysiological characteristics of neurons. Prog Neurobiol. 1990; 35: 1–51. 2217820

7. Bisby MA, Tetzlaff W. Changes in cytoskeletal protein synthesis following axon injury and during regeneration. Mol Neurobiol. 1992; 6: 107–123. doi: 10.1007/BF02780547 1476674

8. Wiberg R, Kingham PJ, Novikova LN. A morphological and molecular characterization of the spinal cord after ventral root avulsion or distal peripheral nerve axotomy injuries in adult rats. J Neurotrauma. 2017; 34: 652–660. doi: 10.1089/neu.2015.4378 27297543

9. Alvarez FJ, Titus-Mitchell HE, Bullinger KL, Kraszpulski M, Nardelli P, Cope TC. Permanent central synaptic disconnection of proprioceptors after nerve injury and regeneration. I. Loss of VGLUT1/IA synapses on motoneurons. J Neurophysiol. 2011; 106: 2450–2470. doi: 10.1152/jn.01095.2010 21832035

10. Rotterman TM, Nardelli P, Cope TC, Alvarez FJ. Normal distribution of VGLUT1 synapses on spinal motoneuron dendrites and their reorganization after nerve injury. J Neurosci. 2014; 34: 3475–3492. doi: 10.1523/JNEUROSCI.4768-13.2014 24599449

11. Bowe CM, Nyle HE, Vlacha V. Progressive morphological abnormalities observed in rat spinal motor neurons at extended intervals after axonal regeneration. J Comp Neurol. 1992; 312: 576–590.

12. O’Hanlon GM, Lowrie MB. Nerve injury in adult rats causes abnormalities in the motoneuron dendritic field that differ from those seen following neonatal nerve injury. Exp Brain Res. 1995; 103: 243–250. doi: 10.1007/bf00231710 7789431

13. Brännström T, Havton I, Kellerth J-O. Changes in size and dendritic arborization patterns of adult cat spinal α-motoneurons following permanent axotomy. J Comp Neurol. 1992a; 318: 439–451. doi: 10.1002/cne.903180408 1578011

14. Sumner BEH, Watson WE. Retraction and expansion of the dendritic tree of motor neurons of adult rats induced in vivo. Nature. 1971; 233: 273–275. doi: 10.1038/233273a0 4938371

15. Brännström T, Havton I, Kellerth J-O. Restorative effects of reinnervation on the size and dendritic arborization patterns of axotomized cat spinal α-motoneurons. J Comp Neurol. 1992b; 318: 452–461. doi: 10.1002/cne.903180409 1578012

16. Standler NA, Bernstein JJ. Degeneration and regeneration of motoneuron dendrites after ventral root crush: Computer reconstruction of dendritic fields. Exp Neurol. 1982; 75: 600–615. doi: 10.1016/0014-4886(82)90028-0 7060690

17. Rose PK, Odlozinski M. Expansion of the dendritic tree of motoneurons innervating neck muscles of the adult cat after permanent axotomy. J Comp Neurol. 1998; 390: 392–411. doi: 10.1002/(sici)1096-9861(19980119)390:3<392::aid-cne7>3.0.co;2-x 9455900

18. Yang LY, Verhovshek T, Sengelaub DR. BDNF and androgen interact in the maintenance of dendritic morphology in a sexually dimorphic rat spinal nucleus. Endocrinology. 2004; 145: 161–168. doi: 10.1210/en.2003-0853 14512438

19. Brushart TM. Preferential reinnervation of motor nerves by regenerating motor axons. J Neurosci. 1988; 8: 1026–1031. 3346713

20. O’Daly A, Rohde C, Brushart T. The topographic specificity of muscle reinnervation predicts function. Eur J Neurosci. 2015; 43: 443–450. doi: 10.1111/ejn.13058 26332647

21. Navarro X, Vivo M, Valero-Cabre A. Neural plasticity after peripheral nerve injury and regeneration. Prog Neurobiol. 2007; 82: 163–201. doi: 10.1016/j.pneurobio.2007.06.005 17643733

22. Socolovsky M, Malessy M, Lopez D, Guedes F, Flores L. Current concepts in plasticity and nerve transfers: relationship between surgical techniques and outcomes. Neurosurg Focus. 2017; 42: E13.

23. Britt JM, Kane JR, Spaeth CS, Zuzek A, Robinson GL, Gbanaglo MY, et al. Polyethylene glycol rapidly restores axonal integrity and improves the rate of motor behavior recovery after sciatic nerve crush injury. J Neurophysiol. 2010; 104: 695–703. doi: 10.1152/jn.01051.2009 20445038

24. Ghergherehchi CL, Bittner GD, Hastings RL, Mikesh M, Riley DC, Trevino RC, et al. Effects of extracellular calcium and surgical techniques on restoration of axonal continuity by polyethylene glycol fusion following complete cut or crush severance of rat sciatic nerves. J Neurosci Res. 2016; 94: 231–245. doi: 10.1002/jnr.23704 26728662

25. Mikesh M, Ghergherehchi CL, Hastings RL, Ali A, Rahesh S, Jagannath K, et al. Polyethylene glycol solutions rapidly restore and maintain axonal continuity, neuromuscular structures and behaviors lost after sciatic nerve transections in female rats. J Neurosci Res. 2018a; 96: 1223–1242. doi: 10.1002/jnr.24225 29659058

26. Mikesh M, Ghergherehchi CL, Rahesh S, Jagannath K, Ali A, Sengelaub DR., et al. Polyethylene glycol treated allografts not tissue matched nor immunosuppressed rapidly repair sciatic nerve gaps, maintain neuromuscular functions, and restore voluntary behaviors in female rats. J Neurosci Res. 2018b; 96: 1243–1264.

27. Riley DC, Bittner GD, Mikesh M, Cardwell NL, Pollins AC, Ghergherehchi CL, et al. Polyethylene glycol-fused allografts produce rapid behavioral recovery after ablation of sciatic nerve segments. J Neurosci Res. 2015; 93: 572–583. doi: 10.1002/jnr.23514 25425242

28. Ghergherehchi CL, Mikesh M, Sengelaub DR, Jackson D., Smith T, Nguyen J, et al. Polyethylene glycol (PEG) and other bioactive solutions with neurorrhaphy for rapid and dramatic repair of peripheral nerve lesions by PEG-fusion. J Neurosci Methods. 2019; 314: 1–12. doi: 10.1016/j.jneumeth.2018.12.015 30586569

29. de Medinaceli L, Freed WJ, Wyatt RJ. An index of the functional condition of rat sciatic nerve based on measurements made from walking tracks. Exp Neurol. 1982; 77: 634–643. doi: 10.1016/0014-4886(82)90234-5 7117467

30. Carlton JM, Goldberg NH. Quantitating integrated muscle function following reinnervation. Surg Forum. 1986; 37: 611–612.

31. Kang H, Tian L, Son YJ, Zuo Y, Procaccino D, Love F, et al. Regulation of the intermediate filament protein nestin at rodent neuromuscular junctions by innervation and activity. J Neurosci. 2007; 27, 5948–5957. doi: 10.1523/JNEUROSCI.0621-07.2007 17537965

32. Kurz EM, Sengelaub DR, Arnold AP. Androgens regulate the dendritic length of mammalian motoneurons in adulthood. Science. 1986; 232: 395–398. doi: 10.1126/science.3961488 3961488

33. Alisky JM, van de Weyering CI, Davidson BL. Widespread dispersal of cholera toxin subunit b to brain and spinal cord neurons following systemic delivery. Exp Neurol. 2002; 178: 139–146. doi: 10.1006/exnr.2002.8031 12460616

34. Lappi D, Feldman J, Sengelaub D, McGaughy J. Nervous system research with RIP conjugates: From determination of function to therapy. In: Stirpe F, Lappi D, editors. Ribosome-inactivating Proteins: Ricin and Related Proteins. New York: Wiley-Blackwell; 2014. pp. 253–269.

35. Molander C, Xu Q, Grant G. The cytoarchitectonic organization of the spinal cord in the rat. I. The lower thoracic and lumbosacral cord. J Comp Neurol. 1984; 230: 133–141. doi: 10.1002/cne.902300112 6512014

36. Nicolopoulos-Stournaras S, lies JF. Motor neuron columns in the lumbar spinal cord of the rat. J Comp Neurol. 1983; 217: 75–85. doi: 10.1002/cne.902170107 6875053

37. Little CM, Coons KD, Sengelaub DR. Neuroprotective effects of testosterone on the morphology and function of somatic motoneurons following the death of neighboring motoneurons. J Comp Neurol. 2009; 512: 359–372. doi: 10.1002/cne.21885 19003970

38. Peyronnard J-M, Charron L. Motor and sensory neurons of the rat sural nerve: a horseradish peroxidase study. Muscle Nerve. 1982; 5: 654–660. doi: 10.1002/mus.880050811 7155177

39. Schrøder HD. Organization of the motoneurons innervating the pelvic muscles of the male rat. J Comp Neurol. 1980; 192: 567–587. doi: 10.1002/cne.901920313 7419745

40. Gundersen HJG. The nucleator. J Microsc. 1988; 151: 3–21. doi: 10.1111/j.1365-2818.1988.tb04609.x 3193456

41. Kurz EM, Brewer RG, Sengelaub DR. Hormonally mediated plasticity of motoneuron morphology in the adult rat spinal cord: a cholera toxin-HRP study. J Neurobiol. 1991; 22: 976–988. doi: 10.1002/neu.480220909 1795161

42. Goldstein LA, Kurz EM, Kalkbrenner AE, Sengelaub DR. Changes in dendritic morphology of rat spinal motoneurons during development and after unilateral target deletion. Dev Brain Res.1993; 73: 151–163.

43. Byers JS, Huguenard AL, Kuruppu D, Liu NK, Xu XM, Sengelaub DR. Neuroprotective effects of testosterone on motoneuron and muscle morphology following spinal cord injury. J Comp Neurol. 2012; 520: 2683–2696. doi: 10.1002/cne.23066 22314886

44. Hebbeler SL, Sengelaub DR. Development of a sexually dimorphic neuromuscular system in male rats after spinal transection: morphologic changes and implications for estrogen sites of action. J Comp Neurol. 2003; 467: 80–96. doi: 10.1002/cne.10911 14574681

45. Lore AB, Hubbell JA, Bobb DS Jr, Ballinger ML, Loftin KL, Smith JW, et al. Rapid induction of functional and morphological continuity between severed ends of mammalian or earthworm myelinated axons. J Neurosci. 1999; 19: 2442–2454. 10087059

46. Rupp A, Dornseifer U, Fischer A, Schmahl W, Rodenacker K, Jutting U, et al. Electrophysiologic assessment of sciatic nerve regeneration in the rat: surrounding limb muscles feature strongly in recordings from the gastrocnemius muscle. J Neurosci Methods. 2007; 166: 266–277. doi: 10.1016/j.jneumeth.2007.07.015 17854904

47. Swett JE, Woolf CJ. The somatotopic organization of primary afferent terminals in the superficial laminae of the dorsal horn of the rat spinal cord. J Comp Neurol. 1985; 231: 66–77. doi: 10.1002/cne.902310106 3968229

48. Badia J, Pascual-Font A, Vivo M, Udina E, Navarro X. Topographical distribution of motor fascicles in the sciatic-tibial nerve of the rat. Muscle Nerve. 2009; 42: 192–201.

49. Christensen MB, Tresco PA. Differences exist in the left and right sciatic nerves of naïve rats and cats. Anat Rec. 2015; 298: 1492–1501.

50. Helmbrecht MS, Soellner H, Castiblanco-Urbina MA, Wizneck S, Sundermeier J, Theis FJ., et al. A critical period for postnatal adaptive plasticity in a model of motor axon miswiring. PLoS One. 2015; 10: e0123643. doi: 10.1371/journal.pone.0123643 25874621

51. de Ruiter GCW, Malessy MJA, Alaid AO, Spinner RJ, Engelstad JK, Sorenson EJ, et al. Misdirection of regenerating motor axons after nerve injury and repair in the rat sciatic nerve model. Exp Neurol. 2007; 211: 339–350.

52. Tung TH, Mackinnon SE. Nerve transfers: Indications, techniques, and outcomes. J Hand Surg Am. 2010; 35: 332–341. doi: 10.1016/j.jhsa.2009.12.002 20141906

53. Miner N. Integumental specification of sensory fibers in the development of cutaneous local sign. J Comp Neurol. 1956; 105: 161–170. doi: 10.1002/cne.901050109 13367248

54. Cameron WE, Averill DB, Berger AJ. Quantitative analysis of the dendrites of cat phrenic motoneurons stained intracellularly with horseradish peroxidase. J Comp Neurol. 1985; 231: 91–101. doi: 10.1002/cne.902310108 3968230

55. Burke RE. Spinal cord: Ventral horn. In: Sheperd GM, editor. The Synaptic Organization of the Brain. New York: Oxford University Press; 1990. pp. 88–132.

56. Chen XY, Wolpaw J.R. Triceps surae motoneuron morphology in the rat: a quantitative light microscopic study. J Comp Neurol. 1994; 343: 143–157. doi: 10.1002/cne.903430111 8027432

57. Cullheim S, Fleshman JW, Glenn LL, Burke RE. Membrane area and dendritic structure in type-identified triceps surae alpha motoneurons. J Comp Neurol. 1987a; 255: 68–81. doi: 10.1002/cne.902550106 3819010

58. Cullheim S, Fleshman JW, Glenn LL, Burke RE. Three-dimensional architecture of dendritic trees in type-identified a-motoneurons. J Comp Neurol. 1987b; 255: 82–96. doi: 10.1002/cne.902550107 3819011

59. Furicchia JV, Goshgarian HG. Dendritic organization of phrenic motoneurons in the adult rat. Exp Neurol. 1987; 96: 621–634. doi: 10.1016/0014-4886(87)90224-x 3446220

60. Schoenen J. Dendritic organization of the human spinal cord: The motoneurons. J Comp Neurol. 1982; 211: 226–247. doi: 10.1002/cne.902110303 7174892

61. Ritz LA, Bailey SM, Murray CR, Sparkes ML. Organizational and morphological features of cat sacrocaudal motoneurons. J Comp Neurol. 1992; 318: 209–221. doi: 10.1002/cne.903180206 1583160

62. Brown PB, Busch GR, Whittington J. Anatomical changes in cat dorsal horn cells after transection of a single dorsal root. Exp Neurol. 1979; 64: 453–468. doi: 10.1016/0014-4886(79)90224-3 89040

Behavioral recovery and spinal motoneuron remodeling after polyethylene glycol fusion repair of singly cut and ablated sciatic nerves

Souhrn

Klíčová slova:

Zdroje

PLOS One

INSIGHTS from European Respiratory Congress

Současné pohledy na riziko v parodontologii

Svět praktické medicíny 3/2024 (znalostní test z časopisu)

Kardiologické projevy hypereozinofilií

Střevní příprava před kolonoskopií