Remote damage after spinal cord injury

Cover Page


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

After spinal cord injury pathological changes in the lesion site and adjacent segments are described in detail. Data are accumulating on the tissue response in the areas of the spinal cord and even the brain distant from the epicentre of spinal cord injury. The concept of plasticity and post-traumatic responses in remote lumbar regions, which contain a specific circuits of interneurons known as the central pattern generator, is particularly important for the recovery of motor function. Among the factors influencing the plasticity of neuronal connections and regenerative potential in the area remote from the lesion epicentre, myeloid infiltration, microglial reactivity, neuroinflammation, and molecular rearrangements of the extracellular matrix are only beginning to be systematically studied. After thoracic spinal cord injury rapid responses develop in the lumbar cord that are characteristic of disintegration of the axons of the descending tracts. These shifts are accompanied by glial reactivity, synapse elimination, imbalance between excitation and inhibition, and disruption of connections in neural networks. This severity of these remote changes depends on the type and severity of the injury, which determines the different involvement and degree of destruction of the descending motor pathways. The review presents an analysis of experimental data on the responses and reorganization of the neural network in the lumbar spinal cord after injury in the proximal regions. The lesional biomarkers are of particular interest as a possible cause of pathological changes in distant areas. These molecules are released from dying cells at the epicenter of injury, appear in the cerebrospinal fluid, and acting as injury-associated molecular patterns and alarmins, can exert a neurotoxic effect in areas remote from the epicenter of injury.

Full Text

Restricted Access

About the authors

Yuri A. Chelyshev

Kazan State Medical University

Author for correspondence.
Email: chelyshev-kzn@yandex.ru
ORCID iD: 0000-0002-6306-5843
SPIN-code: 1570-0209
Scopus Author ID: 190520-003977

M.D., D. Sci. (Med.), Prof., Depart. of Histology, Cytology and Embryology

Russian Federation, Kazan

References

  1. Chelyshev YA, Kabdesh IM, Mukhamedshina YO. Extracellular matrix in neural plasticity and regeneration. Cell Mol Neurobiol. 2022;42(3):647–664. doi: 10.1007/s10571-020-00986-0.
  2. Chelyshev Y. More attention on segments remote from the primary spinal cord lesion site. Front Biosci (Landmark Ed). 2022;27(8):235. doi: 10.31083/j.fbl2708235.
  3. Ohnishi Y, Yamamoto M, Sugiura Y et al. Rostro-caudal different energy metabolism leading to differences in degeneration in spinal cord injury. Brain Commun. 2021;3(2):fcab058. doi: 10.1093/braincomms/fcab058.
  4. Gosgnach S, Bikoff JB, Dougherty KJ et al. Delineating the diversity of spinal interneurons in locomotor Circuits. J Neurosci. 2017;37(45):10835–10841. doi: 10.1523/JNEUROSCI.1829-17.2017.
  5. Fink KL, Cafferty WBJ. Reorganization of intact descending motor circuits to replace lost connections after injury. Neurothe-rapeutics. 2016;13:370–381. doi: 10.1007/s13311-016-0422-x.
  6. Du Beau A, Shakya Shrestha S, Bannatyne BA et al. Neurotransmitter phenotypes of descending systems in the rat lumbar spinal cord. Neuroscience. 2012;227:67–79. doi: 10.1016/j.neuroscience.2012.09.037.
  7. Asboth L, Friedli L, Beauparlant J et al. Cortico-reticulo-spinal circuit reorganization enables functional recovery after severe spinal cord contusion. Nat Neurosci. 2018;21(4):576–588. doi: 10.1038/s41593-018-0093-5.
  8. Gazula VR, Roberts M, Luzzio C et al. Effects of limb exercise after spinal cord injury on motor neuron dendrite structure. J Comp Neurol. 2004;476(2):130–145. doi: 10.1002/cne.20204. PMID: 15248194.
  9. Liu N-K, Byers JS, Lam T et al. Inhibition of cPLA2 has neuroprotective effects on motoneuron and muscle atrophy following spinal cord injury. J Neurotrauma. 2014;38(9):1327–1337. doi: 10.1089/neu.2014.3690.
  10. Matson KJE, Russ DE, Kathe C et al. Single cell atlas of spinal cord injury in mice reveals a pro-regenerative signature in spinocerebellar neurons. Nat Commun. 2022;13(1):5628. doi: 10.1038/s41467-022-33184-1.
  11. Khalki L, Sadlaoud K, Lerond J et al. Changes in innervation of lumbar motoneurons and organization of premotor network following training of transected adult rats. Exp Neurol. 2018;299(Pt A):1–14. doi: 10.1016/j.expneurol.2017.09.002.
  12. Yokota K, Kubota K, Kobayakawa K et al. Pathological changes of distal motor neurons after complete spinal cord injury. Mol Brain. 2019;12(1):4. doi: 10.1186/s13041-018-0422-3.
  13. Fouad K, Rank MM, Vavrek R et al. Locomotion after spinal cord injury depends on constitutive activity in serotonin receptors. J Neurophysiol. 2010;104(6):2975–2984. doi: 10.1152/jn.00499.2010.
  14. Kathe C, Skinnider MA, Hutson TH et al. The neurons that restore walking after paralysis. Nature. 2022;611(7936):540–547. doi: 10.1038/s41586-022-05385-7.
  15. Anderson MA, Squair JW, Gautier M et al. Natural and targeted circuit reorganization after spinal cord injury. Nat Neurosci. 2022;25(12):1584–1596. doi: 10.1038/s41593-022-01196-1.
  16. Chen B, Li Y, Yu B et al. Reactivation of dormant relay pathways in injured spinal cord by KCC2 manipulations. Cell. 2018;174(3):521.e13–535.e13. doi: 10.1016/j.cell.2018.06.005.
  17. Hansen CN, Norden DM, Faw TD et al. Lumbar myeloid cell trafficking into locomotor networks after thoracic spinal cord injury. Exp Neurol. 2016;282:86–98. doi: 10.1016/j.expneurol.2016.05.019.
  18. Mazzone GL, Mohammadshirazi A, Aquino JB et al. GABAergic mechanisms can redress the tilted balance between excitation and inhibition in damaged spinal networks. Mol Neurobiol. 2021;58(8):3769–3786. doi: 10.1007/s12035-021-02370-5.
  19. Liabeuf S, Stuhl-Gourmand L, Gackière F et al. Prochlorperazine increases KCC2 function and reduces spasticity after spinal cord injury. J Neurotrauma. 2017;34(24):3397–3406. doi: 10.1089/neu.2017.5152.
  20. Han Q, Ordaz JD, Liu NK et al. Descending motor circuitry required for NT-3 mediated locomotor recovery after spinal cord injury in mice. Nat Commun. 2019;10(1):5815. doi: 10.1038/s41467-019-13854-3.
  21. Brommer B, He M, Zhang Z et al. Improving hindlimb locomotor function by non-invasive AAV-mediated manipulations of propriospinal neurons in mice with complete spinal cord injury. Nat Commun. 2021;12(1):781. doi: 10.1038/s41467-021-20980-4.
  22. Kwon BK, Streijger F, Fallah N et al. Cerebrospinal fluid biomarkers to stratify injury severity and predict outcome in human traumatic spinal cord injury. J Neurotrauma. 2017;34(3):567–580. doi: 10.1089/neu.2016.4435.
  23. Yang Z, Bramlett HM, Moghieb A et al. Temporal profile and severity correlation of a panel of rat spinal cord injury protein biomarkers. Mol Neurobiol. 2018;55(3):2174–2184. doi: 10.1007/s12035-017-0424-7.
  24. Albayar AA, Roche A, Swiatkowski P et al. Biomarkers in spinal cord injury: Prognostic insights and future potentials. Front Neurol. 2019;10:27. doi: 10.3389/fneur.2019.00027.
  25. Holmström U, Tsitsopoulos PP, Holtz A et al. Cerebrospinal fluid levels of GFAP and pNF-H are elevated in patients with chronic spinal cord injury and neurological deterioration. Acta Neurochir (Wien). 2020;162(9):2075–2086. doi: 10.1007/s00701-020-04422-6.
  26. Wang KKW, Kobeissy FH, Shakkour Z, Tyndall JA. Thorough overview of ubiquitin C-terminal hydrolase-L1 and glial fibrillary acidic protein as tandem biomarkers recently cleared by US Food and Drug Administration for the evaluation of intracranial injuries among patients with traumatic brain injury. Acute Med Surg. 2021;8(1):e622. doi: 10.1002/ams2.622.
  27. Chmielewska N, Szyndler J, Makowska K et al. Looking for novel, brain-derived, peripheral biomarkers of neurological disorders. Neurol Neurochir Pol. 2018;52:318–325. doi: 10.1016/j.pjnns.2018.02.002.
  28. De Menezes MF, Nicola F, da Silva IRV et al. Glial fibrillary acidic protein levels are associated with global histone H4 acetylation after spinal cord injury in rats. Neural Regen Res. 2018;13(11):1945–1952. doi: 10.4103/1673-5374.239443.
  29. Nguyen T, Mao Y, Sutherland T, Gorrie CA. Neural progenitor cells but not astrocytes respond distally to thoracic spinal cord injury in rat models. Neural Regen Res. 2017;12(11):1885–1894. doi: 10.4103/1673-5374.219051.
  30. Gwak YS, Kang J, Unabia GC, Hulsebosch CE. Spatial and temporal activation of spinal glial cells: Role of gliopathy in central neuropathic pain following spinal cord injury in rats. Exp Neurol. 2012;234:362–372. doi: 10.1016/j.expneurol.2011.10.010.
  31. Minta K, Brinkmalm G, Thelin EP et al. Cerebrospinal fluid brevican and neurocan fragment patterns in human traumatic brain injury. Clin Chim Acta. 2021;512:74–83. doi: 10.1016/j.cca.2020.11.017.
  32. Abeysinghe HC, Phillips EL, Chin-Cheng H et al. Modulating astrocyte transition after stroke to promote brain rescue and functional recovery: Emerging targets include Rho kinase. Int J Mol Sci. 2016;17(3):288. doi: 10.3390/ijms17030288.
  33. Schmitz J, Owyang A, Oldham E et al. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity. 2005;23(5):479–490. doi: 10.1016/j.immuni.2005.09.015.
  34. Braun M, Vaibhav K, Saad NM et al. White matter damage after traumatic brain injury: A role for damage associated molecular patterns. Biochim Biophys Acta Mol Basis Dis. 2017;1863(10(Pt B)):2614–2626. doi: 10.1016/j.bbadis.2017.05.020.
  35. Chen R, Kang R, Tang D. The mechanism of HMGB1 secretion and release. Exp Mol Med. 2022;54(2):91–102. doi: 10.1038/s12276-022-00736-w.
  36. Papatheodorou A, Stein A, Bank M et al. High-mobility group box 1 (HMGB1) is elevated systemically in persons with acute or chronic traumatic spinal cord injury. J Neurotrauma. 2017;34(3):746–754. doi: 10.1089/neu.2016.4596.
  37. Fan H, Tang HB, Chen Z et al. Inhibiting HMGB1-RAGE axis prevents pro-inflammatory macrophages/microglia polari-zation and affords neuroprotection after spinal cord injury. J Neuroinflammation. 2020;17(1):295. doi: 10.1186/s12974-020-01973-4.
  38. Wang H, Liu NK, Zhang YP et al. Treadmill training induced lumbar motoneuron dendritic plasticity and behavior recovery in adult rats after a thoracic contusive spinal cord injury. Exp Neurol. 2015;271:368–378. doi: 10.1016/j.expneurol.2015.07.004.
  39. McKay SM, Brooks DJ, Hu P, McLachlan EM. Distinct types of microglial activation in white and grey matter of rat lumbosacral cord after mid-thoracic spinal transection. J Neuropathol Exp Neurol. 2007;66:698–710. doi: 10.1097/nen.0b013e3181256b32.
  40. Detloff MR, Fisher LC, McGaughy V et al. Remote activation of microglia and pro-inflammatory cytokines predict the onset and severity of below-level neuropathic pain after spinal cord injury in rats. Exp Neurol. 2008;212(2):337–347. doi: 10.1016/j.expneurol.2008.04.009.
  41. Honjoh K, Nakajima H, Hirai T et al. Relationship of inflammatory cytokines from M1-type microglia/macrophages at the injured site and lumbar enlargement with neuropathic pain after spinal cord injury in the CCL21 knockout (plt) mouse. Front Cell Neurosci. 2019;13:525. doi: 10.3389/fncel.2019.00525.
  42. Nakajima H, Honjoh K, Watanabe S et al. Distribution and polarization of microglia and macrophages at injured sites and the lumbar enlargement after spinal cord injury. Neurosci Lett. 2020;737:135152. doi: 10.1016/j.neulet.2020.135152.
  43. Norden DM, Faw TD, McKim DB et al. Bone marrow-derived monocytes drive the inflammatory microenvironment in local and remote regions after thoracic spinal cord injury. J Neurotrauma. 2019;36(6):937–949. doi: 10.1089/neu.2018.5806.
  44. Andrews EM, Richards RJ, Yin FQ et al. Alterations inchondroitin sulfate proteoglycan expression occur both at and far from the site of spinal contusion injury. Exp Neurol. 2012;235(1):174–187. doi: 10.1016/j.expneurol.2011.09.008.
  45. David G, Pfyffer D, Vallotton K et al. Longitudinal changes of spinal cord grey and white matter following spinal cord injury. J Neurol Neurosurg Psychiatry. 2021;92(11):1222–1230. doi: 10.1136/jnnp-2021-326337.

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2023 Eco-Vector



СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 75562 от 12 апреля 2019 года.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies