TSitologiya i Genetika 2022, vol. 56, no. 2, 21-37
Cytology and Genetics 2022, vol. 56, no. 2, 125–138, doi: https://www.doi.org/10.3103/S0095452722020086

The effect of implanting fibrin matrix, associated with neonatal brain cells, on the course of experimental spinal cord injury

Medvediev V.V., Oleksenko N.P., Pichkur L.D., Verbovska S.A., Savosko S.I., Draguntsova N.G., Lontkovskiy Yu.A., Vaslovych V.V., Tsymbalyuk V.I.

  1. Bogomolets National Medical University, 13,Tarasa Shevchenka Blv, Kyiv, 01601, Ukraine
  2. SI «Romodanov Neurosurgery Institute, National Academy of Medical Sciences of Ukraine» 32, Platona Mayborody Str., Kyiv, 04050, Ukraine
  3. Kamyanets-Podilsky city state hospital, 31, Pushkins’ka St., Kamianets-Podilskyi, Khmelnytskyi Oblast, 32301, Ukrainе
  4. National Academy of Medical Sciences of Ukraine, 12, Gercena St., Kyiv, 04050, Ukraine

SUMMARY. The efficacy of immediate implantation of fibrin matrix, associated with allogeneic neonatal brain neural cells of rats was investigated in a spinal cord injury (SCI) model. The animals used were white adult outbred rats (~260 g, 4–5 months old). The SCI model was a left-sided hemisection at the level of ~T13–L1 segments. The rehabilitation treatment consisted in the immediate transplantation of the human fibrin matrix, associated with rat neonatal brain cells (NBC, n = 9), into the injury area. The reference groups had isolated SCI (trauma, Tr, n = 7) and implantation of the human fibrin matrix only (Fb, n = 6) into the injury area. The assessment of motor activity of the paretic limb was conducted using the BBB scale, the assessment of spasticity – the Ashworth scale; the histological examination – silver impregnation staining of the spinal cord longitudinal sections obtained in the remote period of injury. The fibrin matrix promotes the activity, growth, and differentiation of the incorporated NBC. Starting from the 2nd to the 3rd week after implantation, the level of the motor function in groups Fb and NBC corresponded to ~11 points of BBB, in Tr group – ~6 points of BBB. No significant differences in this indicator between the NBC and Fb groups and between the Fb and Tr groups were recorded throughout the experiment; significant differences between the NBC and Tr groups were detected at 2 weeks, 1, 2, 3, and 5 months after injury modeling. A significant advantage of the spasticity level in the Tr group over the NBC and Fb groups was found at 6 and 7 weeks after the injury, respectively. Immediate implantation of the fibrin matrix in complex with NBC has a significant positive effect on the restoration of the motor function after laceration SCI.

Keywords: neurotransplantation, fibrin matrix, spinal cord injury, neonatal brain cells, locomotor function restoration, spasticity

TSitologiya i Genetika
2022, vol. 56, no. 2, 21-37

Current Issue
Cytology and Genetics
2022, vol. 56, no. 2, 125–138,
doi: 10.3103/S0095452722020086

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Abbaszadeh, H.-A., Tiraihi, T., Delshad, A., et al., Differentiation of neurosphere-derived rat neural stem cells into oligodendrocyte-like cells by repressing PDGF-α and Olig2 with triiodothyronine, Tissue Cell, 2014, vol. 46, no. 6, pp. 462–469. https://doi.org/10.1016/j.tice.2014.08.003 Article CAS PubMed Google Scholar Amable, P.R., Carias, R.B.V., Teixeira, M.V.T., et al., Platelet-rich plasma preparation for regenerative medicine: optimization and quantification of cytokines and growth factors, Stem Cell Res. Ther., 2013, vol. 4, no. 3, art. ID 67. https://doi.org/10.1186/scrt218 Article CAS PubMed PubMed Central Google Scholar Arvanian, V.L., Schnell, L., Lou, L., et al., Chronic spinal hemisection in rats induces a progressive decline in transmission in uninjured fibers to motoneurons, Exp. Neurol., 2009, vol. 216, no. 2, pp. 471–480. https://doi.org/10.1016/j.expneurol.2009.01.004 Article PubMed PubMed Central Google Scholar Assinck, P., Duncan, G.J., Hilton, B.J., et al., Cell transplantation therapy for spinal cord injury, Nat. Neurosci., 2017, vol. 20, no. 5, pp. 637–647. https://doi.org/10.1016/j.stemcr.2020.05.017 Article CAS PubMed Google Scholar Basso, D.M., Beattie, M.S., and Bresnahan, J.C., A sensitive and reliable locomotor rating scale for open field testing in rats, J. Neurotrauma, 1995, vol. 12, no. 1, pp. 1–21. https://doi.org/10.1089/neu.1995.12.1 Article CAS PubMed Google Scholar Bento, A.R., Quelhas, P., Oliveira, M.J., et al., Three-dimensional culture of single embryonic stem-derived neural/stem progenitor cells in fibrin hydrogels: neuronal network formation and matrix remodeling, J. Tissue Eng. Regen. Med., 2017, vol. 11, no. 12, pp. 3494–3507. https://doi.org/10.1002/term.2262 Article CAS PubMed Google Scholar Blesch, A. and Tuszynski, M.H., Spinal cord injury: plasticity, regeneration and the challenge of translational drug development, Trends Neurosci., 2009, vol. 32, no. 1, pp. 41–47. https://doi.org/10.1016/j.tins.2008.09.008 Article CAS PubMed Google Scholar Brown, A. and Martinez, M., From cortex to cord: motor circuit plasticity after spinal cord injury, Neural Regener. Res., 2019, vol. 14, no. 12, pp. 2054–2062. https://doi.org/10.4103/1673-5374.262572 Article Google Scholar Burns, A.S., Marino, R.J., Kalsi-Ryan, S., Middleton, J.W., Tetreault, L.A., Dettori, J.R., Mihalovich, K.E., and Fehlings, M.G., Type and timing of rehabilitation following acute and subacute spinal cord injury: a systematic review, Global Spine J., 2017, vol. 7, no. 3, 175–194. https://doi.org/10.1177/2192568217703084 Article Google Scholar Cargnello, M. and Roux, P.P., Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases, Mol. Biol. Rev., 2011, vol. 75, no. 1, pp. 50–83. https://doi.org/10.1128/MMBR.00031-10 Article CAS Google Scholar Carlson, S.W. and Saatman, K.E., Central infusion of IGF-1 increases hyppocampal neurogenesis and improves neurobehavioral function following traumatic brain injury, J. Neurotrauma, 2018, vol. 35, no. 13, pp. 1467–1480. https://doi.org/10.1089/neu.2017.5374 Article PubMed PubMed Central Google Scholar Carriel, V., Garrido-Gomez, J., Hernandez-Cortes, P., et al., Combination of fibrin-agarose hydrogels and adipose-derived mesenchymal stem cells for peripheral nerve regeneration, J. Neural Eng., 2013, vol. 10, no. 2, art. ID 026022. https://doi.org/10.1088/1741-2560/10/2/026022 Article PubMed Google Scholar Carriel, V., Scionti, G., Campos, F., et al., In vitro characterization of a nanostructered fibrin agarose bio-artificial nerve substitute, J. Tissue Eng. Regener. Med., 2015, vol. 11, no. 5, pp. 1412–1426. https://doi.org/10.1002/term.2039 Article CAS Google Scholar Cizkova, D., Murgoci, A.N., and Cubinkova, V., Spinal cord injury: animal models, imaging tools and the treatment strategies, Neurochem. Res., 2020, vol. 45, no. 1, pp. 134–143. https://doi.org/10.1007/s11064-019-02800-w Article CAS PubMed Google Scholar Cliffer, K.D., Tonra, J.R., Carson, S.R., et al., Consistent repeated M- and H-wave recording in the hind limb of rats, Muscle Nerve, 1998, vol. 21, no. 11, pp. 1405–1413. https://doi.org/10.1002/(sici)1097-4598(199811)21:11<1405::aidmus7>3.0.co;2-d Article CAS PubMed Google Scholar D’Amico, J.M., Condliffe, E.G., Martins, K.J., et al., Recovery of neuronal and network excitability after spinal cord injury and implications for spasticity, Front. Integr. Neurosci., 2014, vol. 8, art. ID 36. https://doi.org/10.3389/fnint.2014.00036 Article PubMed PubMed Central Google Scholar DeVivo, M.J., Epidemiology of traumatic spinal cord injury: trends and future implications, Spinal Cord, 2012, vol. 50, no. 5, pp. 365–372. https://doi.org/10.1038/sc.2011.178 Article CAS PubMed Google Scholar Dietz, V. and Schwab, M.E., From the rodent spinal cord injury model to human application: promises and challenges, J. Neurotrauma., 2017, vol. 34, no. 9, pp. 1826–1830. https://doi.org/10.1089/neu.2016.4513 Article PubMed Google Scholar Dijkers, M.P., Akers, K.G., and Dieffenbach, S., Systematic reviews of clinical benefits of exoskeleton use for gait and mobility in neurologic disorders: a tertiary study, Arch. Phys. Med. Rehabil., 2021, vol. 102, no. 2, pp. 300–313. https://doi.org/10.1016/j.apmr.2019.01.025 Article PubMed Google Scholar Dong, H.W., Wang, L.H., Zhang, M., et al., Decreased dynorphin A (1–17) in the spinal cord of spastic rats after the compressive injury, Brain Res. Bull., 2005, vol. 67, no. 3, pp. 189–195. https://doi.org/10.1016/j.brainresbull.2005.06.026 Article CAS PubMed Google Scholar Finnerup, N.B., Norrbrink, C., Trok, K., et al., Phenotypes and predictors of pain following traumatic spinal cord injury: a prospective study, J. Pain, 2014, vol. 15, no. 1, pp. 40–48. https://doi.org/10.1016/j.jpain.2013.09.008 Article PubMed Google Scholar Flynn, J.R., Graham, B.A., Galea, M.P., et al., The role of propriospinal interneurons in recovery from spinal cord injury, Neuropharmacology, 2011, vol. 60, no. 5, pp. 809–822. https://doi.org/10.1016/j.neuropharm.2011.01.016 Article CAS PubMed Google Scholar Garcia, E., Aguilar-Cevallos, J., Silva-Garcia, R., et al., Cytokine and growth factor activation in vivo and in vitro after spinal cord injury, Mediators Inflammation, 2016, vol. 2016, art. ID 9476020. https://doi.org/10.1155/2016/9476020 Article CAS Google Scholar GBD 2016 Traumatic Brain Injury and Spinal Cord Injury Collaborators, Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990–2016: a systematic analysis for the Global Burden of Disease Study, Lancet Neurol., 2019, vol. 18, no. 1, pp. 56–87. https://doi.org/10.1016/S1474-4422(18)30415-0 Gilerovich, E.G., Moshonkina, T.R., Fedorova, E.A., et al., Morphofunctional characteristics of the lumbar enlargement of the spinal cord in rats, Neurosci. Behav. Physiol., 2008, vol. 38, no. 8, pp. 855–860. https://doi.org/10.1007/s11055-008-9056-8 Article CAS PubMed Google Scholar Gonzalez-Perez, O., Romero-Rodriguez, R., Soriano-Navarro, M., et al., Epidermal growth factor induces the progeny of subventricular zone type B cells to migrate and differentiate into oligodendrocytes, Stem Cells, 2009, vol. 27, no. 8, pp. 2032–2043. https://doi.org/10.1002/stem.119 Article CAS PubMed PubMed Central Google Scholar Hamid, R., Averbeck, M.A., Chiang, H., et al., Epidemiology and pathophysiology of neurogenic bladder after spinal cord injury, World J. Urol., 2018, vol. 36, no. 10, pp. 1517–1527. https://doi.org/10.1007/s00345-018-2301-z Article PubMed Google Scholar Hill, R.A., Patel, K.D., Medved, J., et al., NG2 cells in white matter but not gray matter proliferate in response to PDGF, J. Neurosci., 2013, vol. 33, no. 36, pp. 14558–14566. https://doi.org/10.1523/JNEUROSCI.2001-12.2013 Article CAS PubMed PubMed Central Google Scholar Holtz, K.A., Lipson, R., Noonan, V.K., et al., Prevalence and effect of problematic spasticity after traumatic spinal cord injury, Arch. Phys. Med. Rehabil., 2017, vol. 98, no. 6, pp. 1132–1138. https://doi.org/10.1016/j.apmr.2016.09.124 Article PubMed Google Scholar Hotwani, K. and Sharma, K., Platelet rich fibrin—a novel acumen into regenerative endodontic therapy, Restor. Dent. Endod., 2014, vol. 39, no.1, pp. 1–6. https://doi.org/10.5395/rde.2014.39.1.1 Article PubMed PubMed Central Google Scholar Hsieh, T.H., Tsai, J.Y., Wu, Y.N., et al., Time course quantification of spastic hypertonia following spinal hemisection in rats, Neuroscience, 2010, vol. 167, no. 1, pp. 185–198. https://doi.org/10.1016/j.neuroscience.2010.01.064 Article CAS PubMed Google Scholar Jeong, H.J., Yun, Y., Lee, S.J., et al., Biomaterials and strategies for repairing spinal cord lesions, Neurochem. Int., 2021, vol. 144, art. ID, 104973. https://doi.org/10.1016/j.neuint.2021.104973 Johnson, P.J., Parker, S.R., and Sakiyama-Elbert, S.E., Fibrin-based tissue engineering scaffolds enhance neural fiber sprouting and delay the accumulation of reactive astrocytes at the lesion in a subacute model of spinal cord injury, J. Biomed. Mater. Res., Part A, 2010, vol. 92, no. 1, pp. 152–163. https://doi.org/10.1002/jbm.a.32343 Article CAS Google Scholar Khan, S., Mafi, P., Mafi, R., et al., A systematic review of mesenchymal stem cells in spinal cord injury, intervertebral disc repair and spinal fusion, Curr. Stem Cell Res. Ther., 2018, vol. 13, no. 4, pp. 316–323. https://doi.org/10.2174/1574888x11666170907120030 Article CAS PubMed Google Scholar Khorasanizadeh, M., Yousefifard, M., Eskian, M., et al., Neurological recovery following traumatic spinal cord injury: a systematic review and meta-analysis, J. Neurosurg. Spine, 2019, vol. 15, pp. 1–17. https://doi.org/10.3171/2018.10.SPINE 18802 Ko, C.C., Tu, T.H., Wu, J.C., et al., Acidic fibroblast growth factor in spinal cord injury, Neurospine, 2019, vol. 16, no. 4, pp. 728–738. https://doi.org/10.14245/ns.1836216.108 Article PubMed PubMed Central Google Scholar Kolomiytsev, A.K., Chaikovskiy, I.B., and Tereshchenko, T.L., Rapid method of silver nitrate impregnation of elements of the peripheral nervous system suitable for paraffin and celloidin sections, Arkh. Anat., Gistol. Embriol., 1981, vol. 81, no. 8, pp. 93–96. Google Scholar Kopach, O., Medvediev, V., Krotov, V., et al., Opposite, bidirectional shifts in excitation and inhibition in specific types of dorsal horn interneurons are associated with spasticity and pain post-SCI, Sci. Rep., 2017, vol. 7, no. 1, art. ID 5884. https://doi.org/10.1038/s41598-017-06049-7 Article CAS PubMed PubMed Central Google Scholar Lemmon, V.P., Ferguson, A.R., Popovich, P.G., et al., MIASCI Consortium, Minimum information about a spinal cord injury experiment: a proposed reporting standard for spinal cord injury experiments, J. Neurotrauma, 2014, vol. 31, no. 15, vol. 1354–1361. https://doi.org/10.1089/neu.2014.3400 Li, J.A., Zhao, C.F., Li, S.J. et al., Modified insulinlike growth factor 1 containing collagen-binding domain for nerve regeneration, Neural Regener. Res., 2018, vol. 13, no. 2, pp. 298–303. https://doi.org/10.4103/1673-5374.226400 Article CAS Google Scholar Li, L.S., Yu, H., Raynald, R., et al., Anatomical mechanism of spontaneous recovery in regions caudal to thoracic spinal cord injury lesions in rats, PeerJ., 2017, vol. 5, art. ID e2865. https://doi.org/10.7717/peerj.2865 Article PubMed PubMed Central Google Scholar Lin, L., Lin, H., Bai, S., et al., Bone marrow mesenchymal stem cells (BMSCs) improved functional recovery of spinal cord injury partly by promoting axonal regeneration, Neurochemistry, 2018, vol. 115, pp. 80–84. https://doi.org/10.1016/j.neuint.2018.02.007 Article CAS Google Scholar Litvinov, R.I., Gorkun, O.V., Owen, S.F., et al., Polymerization of fibrin: specificity, strength, and stability of knob-hole interactions studied at the single-molecule level, Blood, 2005, vol. 106, no. 9, pp. 2944–2951. https://doi.org/10.1182/blood-2005-05-2039 Article CAS PubMed PubMed Central Google Scholar Liu, S., Schackel, T., Weidner, N., and Puttagunta, R., Biomaterial-supported cell transplantation treatments for spinal cord injury: challenges and perspectives, Front. Cell. Neurosci., 2018, vol. 11, art. ID 430. https://doi.org/10.3389/fncel.2017.00430 Article CAS PubMed PubMed Central Google Scholar Liu, S., Xie, Y.Y., and Wang, B., Role and prospects of regenerative biomaterials in the repair of spinal cord injury, Neural Regener. Res., 2019, vol. 14, no. 8, pp. 1352–1363. https://doi.org/10.4103/1673-5374.253512 Article Google Scholar Lu, P., Wang, Y., Graham, L. et al., Long-distance growth and connectivity of neural stem cells after severe spinal cord injury, Cell, 2012, vol. 150, no. 6, pp. 1264–1273. https://doi.org/10.1016/j.cell.2012.08.020 Article CAS PubMed PubMed Central Google Scholar Lu, P., Grahman, L., Wang, Y., et al., Promotion of survival and differentiation of neural stem cells with fibrin and growth factor coctails after severe spinal cord injury, J. Visualized Exp., 2014, vol. 89, art. ID e50641. https://doi.org/10.3791/50641 Article CAS Google Scholar Majczynski, H. and Slawinska, U., Locomotor recovery after thoracic spinal cord lesions in cats, rats and humans, Acta Neurobiol. Exp., 2007, vol. 67, no. 3, pp. 235–257. Google Scholar Metz, G.A., Merkler, D., Dietz, V., et al., Efficient testing of motor function in spinal cord injured rats, Brain Res., 2000, vol. 883, no. 2, pp. 165–177. https://doi.org/10.1016/s0006-8993 (00)02778-5 Mills, C.D., Hains, B.C., Johnson, K.M., et al., Strain and model differences in behavioral outcomes after spinal cord injury in rat, J. Neurotrauma, 2001, vol. 18, no. 8, pp. 743– 756. https://doi.org/10.1089/089771501316919111 Article CAS PubMed Google Scholar Moonen, G., Satkunendrarajah, K., Wilcox, J.T., et al., A New acute impact-compression lumbar spinal cord injury model in the rodent, J. Neurotrauma, 2016, vol. 33, no. 3, pp. 278–289. https://doi.org/10.1089/neu.2015.3937 Article PubMed PubMed Central Google Scholar Muheremu, A., Peng, J., and Ao, Q., Stem cell based therapies for spinal cord injury, Tissue Cell, 2016, vol. 48, no. 4, pp. 328–333. https://doi.org/10.1016/j.tice.2016.05.008 Article PubMed Google Scholar Muller, Ì.F., Ris, I., and Ferry, J.D., Electron microscopy of fine fibrin clots and fine and coarse fibrin films. Observations of fibers in cross-section and in deformed states, J. Mol. Biol., 1984, vol. 174, no. 2, pp. 369–384. https://doi.org/10.1016/0022-2836(84)90343-7 Article CAS PubMed Google Scholar Oliveri, R.S., Bello, S., and Biering-Sørensen, F., Mesenchymal stem cells improve locomotor recovery in traumatic spinal cord injury: systematic review with meta-analyses of rat models, Neurobiol. Dis., 2014, vol. 62, pp. 338–353. https://doi.org/10.1016/j.nbd.2013.10.014 Article CAS PubMed Google Scholar Olude, M.A., Mustapha, O.A., Ogunbunmi, T.K., et al., The vertebral column, ribs, and sternum of the African giant rat (Cricetomys gambianus Waterhouse), Sci. World J., 2013, vol. 2013, art. ID 973537. https://doi.org/10.1155/2013/973537 Article Google Scholar Ozturk, A.M., Sozbilen, M.C., Sevgili, E., et al., Epidermal growth factor regulate apoptosis and oxidative stress in a rat model of spinal cord injury, Injury, 2018, vol. 49, no. 6, pp. 1038–1045. https://doi.org/10.1016/j.injury.2018.03.021 Article PubMed Google Scholar Özkan, Z.E., Macro-anatomical investigations on the skeletons of mole-rat (Spalax leucodon Nordmann) III. Skeleton axiale, Vet. Arhiv, 2007, vol. 77, pp. 281–289. Google Scholar Park, M.N., Lee, J.Y., Jeong, M.S., et al., The roll of Purkinje cell-derived VEGF in cerebellar astrogliosis in Niemann-Pick type C mice, BMB Rep., 2018, vol. 51, no. 2, pp. 79– 84. https://doi.org/10.5483/bmbrep.2018.51.2.168 Article CAS PubMed PubMed Central Google Scholar Pertici, V., Amendola, J., Laurin, J., et al., The use of poly(N-(2-hydroxypropyl)-methacrylamide) hydrogel to repair a T10 spinal cord hemisection in rat: a behavioural, electrophysiological and anatomical examination, ASN Neuro, 2013, vol. 5, no. 2, art. ID e00114. https://doi.org/10.1042/AN20120082 Article CAS PubMed PubMed Central Google Scholar Pretz, C.R., Kozlowski, A.J., Chen, Y., et al., Trajectories of life satisfaction after spinal cord injury, Arch. Phys. Med. Rehabil., 2016, vol. 97, no. 10, pp. 1706–1713. https://doi.org/10.1016/j.apmr.2016.04.022 Article PubMed Google Scholar Robinson, J. and Lu, P., Optimization of trophic support for stem cell graft in sites of spinal cord injury, Exp. Neurol., 2017, vol. 291, pp. 87–97. https://doi.org/10.1016/j.exp neurol.2017.02.007 Rao, S.N. and Pearse, D.D., Regulating axonal responses to injury: the intersection between signaling pathways involved in axon myelination and the inhibition of axon regeneration, Front. Mol. Neurosci., 2016, vol. 9, art. ID 33.https://doi.org/10.3389/fnmol.2016.00033 Article CAS PubMed PubMed Central Google Scholar Sachdeva, R., Gao, F., Chan, C.C.H., and Krassioukov, A.V., Cognitive function after spinal cord injury: a systematic review, Neurology, 2018, vol. 91, no. 13, pp. 611–621. https://doi.org/10.1212/WNL.0000000000006244 Article PubMed PubMed Central Google Scholar Schuh, C.M., Morton, T.J., Banerjee, A., et al., Activation of Schwann cell-like cells on aligned fibrinpoly (lactic-co-glycolic acid) structures: a novel construct for application in peripheral nerve regeneration, Cells Tissues Organs, 2015, vol. 200, no. 5, pp. 287–299. https://doi.org/10.1159/000437091 Article CAS PubMed Google Scholar Shah, M., Peterson, C., and Yilmaz, E., Current advancements in the management of spinal cord injury: a comprehensive review of literature, Surg. Neurol. Int., 2020, vol. 11, art. ID. 2. https://doi.org/10.25259/SNI_568_2019 Singh, A., Tetreault, L., Kalsi-Ryan, S., et al., Global prevalence and incidence of traumatic spinal cord injury, Clin. Epidemiol., 2014, vol. 23, no. 6, pp. 309–331. https://doi.org/10.2147/CLEP.S68889 Article Google Scholar Steeves, J.D., Bench to bedside: challenges of clinical translation, Prog. Brain Res., 2015, vol. 218, pp. 227–239. https://doi.org/10.1016/bs.pbr.2014.12.008 Article PubMed Google Scholar Swieck, K., Conta-Steencken, A., Middleton, F.A., et al., Effect of lesion proximity on the regenerative response of long descending propriospinal neurons after spinal transection injury, BMC Neurosci., 2019, vol. 20, no. 1, art. ID 10. https://doi.org/10.1186/s12868-019-0491-y Article PubMed PubMed Central Google Scholar Tatullo, M., Marrelli, M., Cassetta, M., et al., Platelet rich fibrin (P.R.F.) in reconstructive surgery of atrophied maxillary bones: Clinical and histological evaluations, Int. J. Med. Sci., 2012, vol. 9, pp. 872–880. https://doi.org/10.7150/ijms.5119 Article PubMed PubMed Central Google Scholar Tran, A.P., Warren, P.M., Silver, J., et al., The biology of regeneration failure and success after spinal cord injury, Physiol. Rev., 2018, vol. 98, no. 2, pp. 881–917. https://doi.org/10.1152/physrev.00017.2017 Article CAS PubMed PubMed Central Google Scholar Wan, F.J., Chien, W.C., Chung, C.H., et al., Association between traumatic spinal cord injury and affective and other psychiatric disorders – A nationwide cohort study and effects of rehabilitation therapies, J. Affective Disord., 2020, vol. 265, vol. 381–388. https://doi.org/10.1016/j.jad.2020.01.063 Wang, Y., Tan, H., and Hui, X., Biomaterial scaffolds in regenerative therapy of the central nervous system, Biomed. Res. Int., 2018, vol. 2018, art. ID 784890.1 https://doi.org/10.1155/2018/7848901 Webb, A.A. and Muir, G.D., Compensatory locomotor adjustments of rats with cervical or thoracic spinal cord hemisections, J. Neurotrauma, 2002, vol. 19, no. 2, vol. 239–256. https://doi.org/10.1089/08977150252806983 Yao, S., Liu, X., Yu, S., et al., Co-effects of matrix low elasticity and aligned topography on stem cell neurogenic differentiation and rapid neurite outgrowth, Nanoscale, 2016, vol. 8, no. 19, pp. 10252–10265. https://doi.org/10.1039/c6nr01169a Article CAS PubMed Google Scholar Zhang, Q., Shi, B., and Ding, J., Polymer scaffolds facilitate spinal cord injury repair, Acta Biomater., 2019, vol. 88, pp. 57–77. https://doi.org/10.1016/j.actbio.2019.01.056 Article CAS PubMed Google Scholar Zhang, Q., Yan, S., You, R., et al., Multichannel silk protein/laminin grafts for spinal cord injury repair, J. Biomed. Mater. Res., Part A, 2016, vol. 104, no. 12, pp. 3045–3057. https://doi.org/10.1002/jbm.a.35851 Article CAS Google Scholar Zhao, Y.Y., Yuan, Y., Chen, Y., et al., Histamine promotes locomotion recovery after spinal cord hemisection via inhibiting astrocytic scar formation, CNS Neurosci. Ther., 2015, vol. 21, no. 5, pp. 454–462. https://doi.org/10.1111/cns.12379