Axotomy: A Model of neurotrauma in the peripheral nervous system
Abstract
Neurotrauma is one of the main causes of disability and death in the world, especially in young and middle-aged men. however, the mechanisms that mediate the survival and death of cells of the peripheral nervous system are still not fully understood. Therefore, studies of the cellular-molecular mechanisms of damage to the peripheral nervous system on model objects are relevant.
MATERIALS AND METHODS: This review focuses on the obtained date from the Laboratory of molecular Neurobiology, the Southern Federal University, plus initial Pubmed search (https://pubmed.ncbi.nlm.nih.gov/), including the unique characteristic and perspectives these axotomy models as an object for studying molecular and cellular changes caused by axotomy of the peripheral nervous system.
RESULTS. In our studies, we used three experimental models of neurotrauma in vertebrates and invertebrates: mechanoreceptor neurons (MRN) and ganglia of the crayfish ventral nerve cord (VNC), as well as the axotomized dorsal root ganglia (DRG) of the rat spinal cord, obtained by the sciatic nerve transection. Thus, the use of these models helps to clarify the complex mechanisms of different types of neurotrauma leading to the death of neurons and glial cells.
CONCLUSION. The acquired knowledge will underlie a theoretical background, which will help to better understand the fundamental mechanisms of survival and death of neurons and glial cells after nerve damage. The discovery of pathways of injury in neurons and glia of axotomized ganglia may identify new targets for the treatment of neurotrauma and its consequences.
Supporting agencies: This study was funded by a grant from the Ministry of Education and Science of the Russian Federation No. 0852-2020-0028 and a stipend from the President of the Russian Federation for young researchers.
About the Author
V. A. Dzreyan
Southern Federal University, Academy of Biology and Biotechnology, Laboratory of Molecular Neurobiology
Russian Federation
Russian Federation
Dzreyan Valentina Aleksandrovna
Rostov-on-Don
References
1. Rishal I, Fainzilber M. Axon-soma communication in neuronal injury. Nat rev Neurosci. 2014;15(1):32–42. doi:10.1038/nrn3609
2. Richardson PM, Miao T, Wu D, Zhang y, Yeh J, Bo X. Responses of the nerve cell body to axotomy. Neurosurgery. 2009;65(4 Suppl): a74-a79. doi:10.1227/01.NeU.0000352378.26755.C3
3. Abe N, Cavalli V. Nerve injury signaling. Curr opin Neurobiol. 2008;18(3):276–283. doi:10.1016/j.conb.2008.06.005
4. Casas C, Isus L, Herrando-Grabulosa M, et al. Network-based proteomic approaches reveal the neurodegenerative, neuroprotective and pain-related mechanisms involved after retrograde axonal damage. Sci rep. 2015;5:9185. published 2015 Mar 18. doi:10.1038/srep09185
5. Gandhi S, Abramov Ay. Mechanism of oxidative stress in neurodegeneration. oxid Med Cell longev. 2012;2012:428010. doi:10.1155/2012/428010
6. Batulan Z, Taylor DM, Aarons RJ, et al. Induction of multiple heat shock proteins and neuroprotection in a primary culture model of familial amyotrophic lateral sclerosis. Neurobiol dis. 2006;24(2):213– 225. doi:10.1016/j.nbd.2006.06.017
7. Li r, Liu Z, Pan Y, Chen l, Zhang Z, Lu L. Peripheral nerve injuries treatment: a systematic review. Cell Biochem Biophys. 2014;68(3):449–454. doi:10.1007/s12013-013-9742-1
8. Wang HC, Ma YB. Experimental models of traumatic axonal injury. j Clin Neurosci. 2010;17(2):157–162. doi:10.1016/j.jocn.2009.07.099
9. Challa SR. Surgical animal models of neuropathic pain: pros and Cons. Int j Neurosci. 2015;125(3):170–174. doi:10.3109/00207454.2014.922559
10. Hill CS, Coleman MP, Menon DK. Traumatic axonal Injury: Mechanisms and Translational opportunities. Trends Neurosci. 2016;39(5):311–324. doi:10.1016/j.tins.2016.03.002
11. Magharious MM, D’Onofrio PM, Koeberle PD. Optic nerve transection: a model of adult neuron apoptosis in the central nervous system. j Vis exp. 2011;(51):2241. published 2011 May 12. doi:10.3791/2241
12. Purice MD, Ray A, Münzel EJ, et al. A novel drosophila injury model reveals severed axons are cleared through a draper/MMp-1 signaling cascade. elife. 2017;6: e23611. published 2017 aug 21. doi:10.7554/elife.23611
13. Nagashima M, Fujikawa C, Mawatari K, Mori Y, Kato S. HSp70, the earliest-induced gene in the zebrafish retina during optic nerve regeneration: its role in cell survival. Neurochem Int. 2011;58(8):888– 895. doi:10.1016/j.neuint.2011.02.017
14. Gower DJ, Hollman C, Lee KS, Tytell M. Spinal cord injury and the stress protein response. j Neurosurg. 1989;70(4):605–611. doi:10.3171/jns.1989.70.4.0605
15. Batulan Z, Taylor DM, Aarons RJ, et al. Induction of multiple heat shock proteins and neuroprotection in a primary culture model of familial amyotrophic lateral sclerosis. Neurobiol dis. 2006;24(2):213– 225. doi:10.1016/j.nbd.2006.06.017
16. Batulan Z, Nalbantoglu J, durham HD. Nonsteroidal anti-inflammatory drugs differentially affect the heat shock response in cultured spinal cord cells. Cell Stress Chaperones. 2005;10(3):185– 196. doi:10.1379/csc-30r.1
17. Newfry GA, Jones KJ. Differential effects of facial nerve transection on heat shock protein 70 expression in the developing and adult hamster facial nucleus. Metab Brain dis. 1998;13(3):253–257. doi:10.1023/a:1023280110386
18. Demyanenko S, Dzreyan V, Uzdensky A. Axotomy-Induced Changes of the protein profile in the Crayfish Ventral Cord ganglia. j Mol Neurosci. 2019;68(4):667–678. doi:10.1007/s12031-019-01329-5
19. Fedorenko GM, Uzdensky AB. dynamics of ultrastructural changes in the isolated crayfish mechanoreceptor neuron under photodynamic impact. j Neurosci res. 2008;86(6):1409–1416. doi:10.1002/jnr.21587
20. Khaitin aM, Rudkovskii MV, Uzdensky AB. The method of isolation of the crayfish abdominal stretch receptor maintaining a connection of the sensory neuron to the ventral nerve cord ganglion. Invert Neurosci. 2015;15(1):176. doi:10.1007/s10158-014-0176-2
21. Rudkovskii MV, Fedorenko AG, Khaitin AM, Pitinova MA, Uzdensky AB. The effect of axotomy on firing and ultrastructure of the crayfish mechanoreceptor neurons and satellite glial cells. Mol Cell Neurosci. 2020;107:103534. doi:10.1016/j.mcn.2020.103534
22. Rodkin S, Khaitin A, Pitinova M, et al. The localization of p53 in the Crayfish Mechanoreceptor Neurons and Its role in axotomy-Induced death of Satellite glial Cells remote from the axon Transection Site. j Mol Neurosci. 2020;70(4):532–541. doi:10.1007/s12031-019-01453-2
23. Demyanenko S, Nikul V, Rodkin S, Davletshin A, Evgen’ev MB, Garbuz DG. Exogenous recombinant Hsp70 mediates neuroprotection after photothrombotic stroke. Cell Stress Chaperones. 2021;26(1):103–114. doi:10.1007/s12192-020-01159-0
24. Purice MD, Ray A, Münzel EJ, et al. A novel drosophila injury model reveals severed axons are cleared through a draper/MMp-1 signaling cascade. elife. 2017;6: e23611. published 2017 aug 21. doi:10.7554/elife.23611
25. Spaeth CS, Fan JD, Spaeth EB, Robison T, Wilcott RW, Bittner GD. Neurite transection produces cytosolic oxidation, which enhances plasmalemmal repair. j Neurosci res. 2012;90(5):945–954. doi:10.1002/jnr.22823
26. Mcgill CH, Bhupanapadu Sunkesula Sr, Poon AD, Mikesh M, Bittner GD. Sealing frequency of B 104 cells declines exponentially with decreasing transection distance from the axon hillock [published correction appears in exp Neurol. 2017 Nov;297:190]. exp Neurol. 2016;279:149–158. doi:10.1016/j.expneurol.2016.02.001
27. Yoo S, Nguyen MP, Fukuda M, Bittner GD, Fishman HM. Plasmalemmal sealing of transected mammalian neurites is a gradual process mediated by Ca(2+)-regulated proteins. j Neurosci res. 2003;74(4):541–551. doi:10.1002/jnr.10771
28. Spira ME, Benbassat D, Dormann A. Resealing of the proximal and distal cut ends of transected axons: electrophysiological and ultrastructural analysis. j Neurobiol. 1993;24(3):300–316. doi:10.1002/neu.480240304
29. Eddleman CS, Smyers ME, Lore A, Fishman HM, Bittner GD. Anomalies associated with dye exclusion as a measure of axolemmal repair in invertebrate axons. Neurosci lett. 1998;256(3):123–126. doi:10.1016/s0304–3940(98)00709-5
30. Lichstein JW, Ballinger ML, Blanchette AR, Fishman HM, Bittner GD. Structural changes at cut ends of earthworm giant axons in the interval between dye barrier formation and neuritic outgrowth. j Comp Neurol. 2000;416(2):143–157. doi:10.1002/(sici)1096-9861(20000110)416:23.0.co;2–3
31. Berezhnaya EV, Bibov MY, Komandirov MA, Neginskaya MA, Rudkovskii MV, Uzdensky AB. Involvement of MapK, akt/gSK-3β and aMpK/mTor signaling pathways in protection of remote glial cells from axotomy-induced necrosis and apoptosis in the isolated crayfish stretch receptor. Mol Cell Neurosci. 2017;83:1–5. doi:10.1016/j.mcn.2017.06.003
32. Fedorenko GM, Uzdensky AB. Dynamics of ultrastructural changes in the isolated crayfish mechanoreceptor neuron under photodynamic impact. j Neurosci res. 2008;86(6):1409–1416. doi:10.1002/jnr.21587
33. Seichter HA, Blumenthal F, Smarandache-Wellmann CR. The swimmeret system of crayfish: a practical guide for the dissection of the nerve cord and extracellular recordings of the motor pattern. j Vis exp. 2014;(93): e52109. published 2014 Nov 25. doi:10.3791/52109
34. Skinner K. The structure of the fourth abdominal ganglion of the crayfish, procambarus clarki (girard). II. Synaptic neuropils. j Comp Neurol. 1985;234(2):182–191. doi:10.1002/cne.902340205
35. Mulloney B, Tschuluun N, Hall WM. Architectonics of crayfish ganglia. Microsc res Tech. 2003;60(3):253–265. doi:10.1002/jemt.10265
36. Attwell CL, Van Zwieten M, Verhaagen J, Mason MRJ. The dorsal Column lesion Model of Spinal Cord Injury and Its Use in deciphering the Neuron-Intrinsic Injury response. dev Neurobiol. 2018;78(10):926–951. doi:10.1002/dneu.22601
37. Esposito MF, Malayil R, Hanes M, Deer T. Unique Characteristics of the dorsal root ganglion as a Target for Neuromodulation. pain Med. 2019;20(Suppl 1): S 23-S 30. doi:10.1093/pm/pnz012
38. Weng YL, Joseph J, An R, Song H, Ming GL. Epigenetic regulation of axonal regenerative capacity. epigenomics. 2016;8(10):1429–1442. doi:10.2217/epi-2016–0058
39. Martin SL, Reid AJ, Verkhratsky A, Magnaghi V, Faroni A. Gene expression changes in dorsal root ganglia following peripheral nerve injury: roles in inflammation, cell death and nociception. Neural regen res. 2019;14(6):939–947. doi:10.4103/1673–5374.250566
40. Dzreyan V, Rodkin S, Nikul V, Pitinova M, Uzdensky A. The expression of e 2F1, p53, and Caspase 3 in the rat dorsal root ganglia after Sciatic Nerve Transection. j Mol Neurosci. 2021;71(4):826–835. doi:10.1007/s12031-020-01705-6
41. Savastano LE, Laurito SR, Fitt MR, Rasmussen JA, Gonzalez Polo V, Patterson SI. Sciatic nerve injury: a simple and subtle model for investigating many aspects of nervous system damage and recovery. j Neurosci Methods. 2014;227:166–180. doi:10.1016/j.jneumeth.2014.01.020
42. Dubový P, Klusáková I, Hradilová-Svíženská I, Joukal M. Expression of regeneration-associated proteins in primary Sensory Neurons and regenerating axons after Nerve Injury-an overview. anat rec (Hoboken). 2018;301(10):1618–1627. doi:10.1002/ar.23843
43. Dzreyan VA, Rodkin SV, Pitinova MA, Uzdensky AB. HdaC 1 expression, Histone deacetylation, and protective role of Sodium Valproate in the rat dorsal root ganglia after Sciatic Nerve Transection. Mol Neurobiol. 2021;58(1):217–228. doi:10.1007/s12035-020-02126-7
44. Abe N, Cavalli V. Nerve injury signaling. Curr opin Neurobiol. 2008;18(3):276–283. doi:10.1016/j.conb.2008.06.005
45. McKay Hart A, Brannstrom T, Wiberg M, Terenghi g. primary sensory neurons and satellite cells after peripheral axotomy in the adult rat: timecourse of cell death and elimination. exp Brain res. 2002;142(3):308–318. doi:10.1007/s00221-001-0929-0
Review
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Dzreyan V.A. Axotomy: A Model of neurotrauma in the peripheral nervous system. Russian Neurosurgical Journal named after Professor A. L. Polenov. 2022;14(2):204-210. (In Russ.)
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