{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T20:07:08Z","timestamp":1778443628282,"version":"3.51.4"},"reference-count":54,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2017,10,24]],"date-time":"2017-10-24T00:00:00Z","timestamp":1508803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Traumatic spinal cord injury (SCI) causes dramatic disability and dysfunction in the motor, sensory and autonomic systems. The severe inflammatory reaction that occurs after SCI is strongly associated with further tissue damage. As such, immunomodulatory strategies have been developed, aimed at reducing inflammation, but also at shaping the immune response in order to protect, repair and promote regeneration of spared neural tissue. One of those promising strategies is the intraspinal administration of the cytokine interleukin-4 (IL-4) that was shown to promote a phenotype on specific immune cells associated with neuroprotection and repair. In this work, we evaluated if a systemic delivery of IL-4 for a 7-days period was also capable of promoting neuroprotection after SCI by analyzing different neural cells populations and motor recovery. IL-4 treatment promoted an elevation of the anti-inflammatory cytokine IL-10 in the serum both at 24 h and 7 days after injury. Locally, treatment with IL-4 led to a reduction on cells expressing markers associated with inflammation, CD11b\/c and iNOS. Importantly, IL-4 treatment increased the neuronal markers \u03b2III-tubulin and NeuN, and the oligodendrocyte marker O4, suggesting a neuroprotective effect. Moreover, 100% of the animals treated with IL-4 were able to recover weight support against only 33% of saline treated animals. Overall, these results show that systemic administration of IL-4 positively impacts different aspects of spinal cord injury, creating a more favorable environment for recovery to take place.<\/jats:p>","DOI":"10.3390\/ph10040083","type":"journal-article","created":{"date-parts":[[2017,10,24]],"date-time":"2017-10-24T10:39:18Z","timestamp":1508841558000},"page":"83","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Systemic Interleukin-4 Administration after Spinal Cord Injury Modulates Inflammation and Promotes Neuroprotection"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4208-2011","authenticated-orcid":false,"given":"Rui","family":"Lima","sequence":"first","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, Braga\/Guimaraes, Portugal"}]},{"given":"Susana","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, Braga\/Guimaraes, Portugal"}]},{"given":"Jos\u00e9","family":"Lopes","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, Braga\/Guimaraes, Portugal"}]},{"given":"Pedro","family":"Barradas","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, Braga\/Guimaraes, Portugal"}]},{"given":"Nat\u00e1lia","family":"Vasconcelos","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, Braga\/Guimaraes, Portugal"}]},{"given":"Eduardo","family":"Gomes","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, Braga\/Guimaraes, Portugal"}]},{"given":"Rita","family":"Assun\u00e7\u00e3o-Silva","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, Braga\/Guimaraes, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1461-9077","authenticated-orcid":false,"given":"F\u00e1bio","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, Braga\/Guimaraes, Portugal"}]},{"given":"M\u00f3nica","family":"Morais","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, Braga\/Guimaraes, Portugal"}]},{"given":"Nuno","family":"Sousa","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, Braga\/Guimaraes, Portugal"}]},{"given":"Ant\u00f3nio","family":"Salgado","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, Braga\/Guimaraes, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1061-1716","authenticated-orcid":false,"given":"Nuno","family":"Silva","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, Braga\/Guimaraes, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2017,10,24]]},"reference":[{"key":"ref_1","unstructured":"National Spinal Cord Injury Statistical Center (2005). Facts and figures at a glance. J. Spinal Cord Med., 28, 379\u2013380."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1002\/(SICI)1096-9861(19970120)377:3<443::AID-CNE10>3.0.CO;2-S","article-title":"Cellular inflammatory response after spinal cord injury in sprague-dawley and lewis rats","volume":"377","author":"Popovich","year":"1997","journal-title":"J. Comp. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/sj.sc.3101483","article-title":"Post-traumatic inflammation following spinal cord injury","volume":"41","author":"Hausmann","year":"2003","journal-title":"Spinal Cord"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1089\/neu.2011.1888","article-title":"Anti-inflammatory treatments during the chronic phase of spinal cord injury improve locomotor function in adult mice","volume":"28","author":"Arnold","year":"2011","journal-title":"J. Neurotrauma"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1006\/exnr.2000.7488","article-title":"Inhibition of monocyte\/macrophage migration to a spinal cord injury site by an antibody to the integrin \u03b1D: A potential new anti-inflammatory treatment","volume":"166","author":"Mabon","year":"2000","journal-title":"Exp. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1056\/NEJM199005173222001","article-title":"A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the second national acute spinal cord injury study","volume":"322","author":"Bracken","year":"1990","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1089\/neu.2015.3963","article-title":"Methylprednisolone for the treatment of patients with acute spinal cord injuries: A propensity score-matched cohort study from a canadian multi-center spinal cord injury registry","volume":"32","author":"Evaniew","year":"2015","journal-title":"J. Neurotrauma"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1227\/NEU.0b013e318276ee7e","article-title":"Updated guidelines for the management of acute cervical spine and spinal cord injury","volume":"72","author":"Resnick","year":"2013","journal-title":"Neurosurgery"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.pneurobio.2013.11.002","article-title":"From basics to clinical: A comprehensive review on spinal cord injury","volume":"114","author":"Silva","year":"2014","journal-title":"Prog. Neurobiol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Shechter, R., London, A., Varol, C., Raposo, C., Cusimano, M., Yovel, G., Rolls, A., Mack, M., Pluchino, S., and Martino, G. (2009). Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice. PLoS Med., 6.","DOI":"10.1371\/journal.pmed.1000113"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.neuron.2015.05.019","article-title":"Dealing with danger in the cns: The response of the immune system to injury","volume":"87","author":"Gadani","year":"2015","journal-title":"Neuron"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1172\/JCI76210","article-title":"MHCII-independent cCD4+ T cells protect injured cns neurons via IL-4","volume":"125","author":"Walsh","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.expneurol.2007.06.009","article-title":"Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury","volume":"209","author":"Donnelly","year":"2008","journal-title":"Exp. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nrn2398","article-title":"Can the immune system be harnessed to repair the CNS?","volume":"9","author":"Popovich","year":"2008","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1186\/s12974-016-0623-6","article-title":"The immunomodulator decoy receptor 3 improves locomotor functional recovery after spinal cord injury","volume":"13","author":"Chiu","year":"2016","journal-title":"J. Neuroinflammation"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.bbi.2014.11.007","article-title":"Adoptive transfer of M2 macrophages promotes locomotor recovery in adult rats after spinal cord injury","volume":"45","author":"Ma","year":"2015","journal-title":"Brain. Behav. Immun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.expneurol.2016.01.002","article-title":"Differential effects of myelin basic protein-activated Th1 and Th2 cells on the local immune microenvironment of injured spinal cord","volume":"277","author":"Hu","year":"2016","journal-title":"Exp. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1002\/glia.23041","article-title":"IL-4 drives microglia and macrophages toward a phenotype conducive for tissue repair and functional recovery after spinal cord injury","volume":"64","year":"2016","journal-title":"Glia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s12974-015-0463-9","article-title":"Cyclic amp is a key regulator of m1 to M2a phenotypic conversion of microglia in the presence of Th2 cytokines","volume":"13","author":"Ghosh","year":"2016","journal-title":"J. Neuroinflammation"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"13435","DOI":"10.1523\/JNEUROSCI.3257-09.2009","article-title":"Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord","volume":"29","author":"Kigerl","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8904","DOI":"10.1523\/JNEUROSCI.1146-14.2014","article-title":"IL-4 signaling drives a unique arginase+\/IL-1\u03b2+ microglia phenotype and recruits macrophages to the inflammatory CNS: Consequences of age-related deficits in IL-4R\u03b1 after traumatic spinal cord injury","volume":"34","author":"Fenn","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4685","DOI":"10.1073\/pnas.88.11.4685","article-title":"Characterization of posttranslational modifications in neuron-specific class III \u03b2-tubulin by mass spectrometry","volume":"88","author":"Alexander","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/0012-1606(81)90477-2","article-title":"Monoclonal antibodies (O1 to O4) to oligodendrocyte cell surfaces: An immunocytological study in the central nervous system","volume":"83","author":"Sommer","year":"1981","journal-title":"Dev. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1073\/pnas.1523212113","article-title":"Beneficial effects of IL-37 after spinal cord injury in mice","volume":"113","author":"Bufler","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1186\/s12974-016-0566-y","article-title":"Interleukin-25 is detrimental for recovery after spinal cord injury in mice","volume":"13","author":"Dooley","year":"2016","journal-title":"J. Neuroinflammation"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1146\/annurev.immunol.19.1.683","article-title":"Interleukin-10 and the interleukin-10 receptor","volume":"19","author":"Moore","year":"2001","journal-title":"Annu. Rev. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/BF00918147","article-title":"Biological properties of interleukin 10","volume":"12","author":"Howard","year":"1992","journal-title":"J. Clin. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1089\/neu.1999.16.851","article-title":"Systemically administered interleukin-10 reduces tumor necrosis factor-alpha production and significantly improves functional recovery following traumatic spinal cord injury in rats","volume":"16","author":"Bethea","year":"1999","journal-title":"J. Neurotrauma"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.expneurol.2009.08.018","article-title":"IL-10 promotes neuronal survival following spinal cord injury","volume":"220","author":"Zhou","year":"2009","journal-title":"Exp. Neurol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1006\/exnr.1999.7173","article-title":"Neuroprotective effects of interleukin-10 following excitotoxic spinal cord injury","volume":"159","author":"Brewer","year":"1999","journal-title":"Exp. Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1523\/JNEUROSCI.3593-06.2007","article-title":"The Ca2+-activated K+ channel KCNN4\/KCa3. 1 contributes to microglia activation and nitric oxide-dependent neurodegeneration","volume":"27","author":"Kaushal","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1523\/JNEUROSCI.5643-07.2008","article-title":"Mechanisms of microglia-mediated neurotoxicity in a new model of the stroke penumbra","volume":"28","author":"Kaushal","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1089\/089771502753754109","article-title":"Temporal and segmental distribution of constitutive and inducible nitric oxide synthases after traumatic spinal cord injury: Effect of aminoguanidine treatment","volume":"19","author":"Chatzipanteli","year":"2002","journal-title":"J. Neurotrauma"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1089\/0897715041651105","article-title":"Increased expression of cyclo-oxygenase 2 and vascular endothelial growth factor in lesioned spinal cord by transplanted olfactory ensheathing cells","volume":"21","author":"Navarro","year":"2004","journal-title":"J. Neurotrauma"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1093\/jnen\/62.11.1096","article-title":"Comparison of inos inhibition by antisense and pharmacological inhibitors after spinal cord injury","volume":"62","author":"Pearse","year":"2003","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3521","DOI":"10.1038\/s41598-017-03780-z","article-title":"Image based machine learning for identification of macrophage subsets","volume":"7","author":"Rostam","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.expneurol.2006.04.028","article-title":"Immune-mediated neuroprotection of axotomized mouse facial motoneurons is dependent on the IL-4\/STAT6 signaling pathway in cd4+ t cells","volume":"201","author":"DeBoy","year":"2006","journal-title":"Exp. Neurol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2721","DOI":"10.1111\/j.1460-9568.2006.05155.x","article-title":"The cytokine\/neurotrophin axis in peripheral axon outgrowth","volume":"24","author":"Uhlmann","year":"2006","journal-title":"Eur. J. Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1002\/jnr.490330218","article-title":"Proliferation and differentiation of O4+ oligodendrocytes in postnatal rat cerebellum: Analysis in unfixed tissue slices using anti-glycolipid antibodies","volume":"33","author":"Warrington","year":"1992","journal-title":"J. Neurosci. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.mcn.2005.10.006","article-title":"Microglia activated by IL-4 or IFN-\u03b3 differentially induce neurogenesis and oligodendrogenesis from adult stem\/progenitor cells","volume":"31","author":"Butovsky","year":"2006","journal-title":"Mol. Cell. Neurosc."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1093\/brain\/123.10.2005","article-title":"TNFR1 signalling is critical for the development of demyelination and the limitation of T-cell responses during immune-mediated cns disease","volume":"123","author":"Probert","year":"2000","journal-title":"Brain"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"a020602","DOI":"10.1101\/cshperspect.a020602","article-title":"Central nervous system regenerative failure: Role of oligodendrocytes, astrocytes, and microglia","volume":"7","author":"Silver","year":"2015","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.conb.2006.09.004","article-title":"The role of extracellular matrix in CNS regeneration","volume":"17","author":"Busch","year":"2007","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.1523\/JNEUROSCI.3547-03.2004","article-title":"Reactive astrocytes protect tissue and preserve function after spinal cord injury","volume":"24","author":"Faulkner","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1038\/nm1425","article-title":"Conditional ablation of STAT3 or SOCS3 discloses a dual role for reactive astrocytes after spinal cord injury","volume":"12","author":"Okada","year":"2006","journal-title":"Nat. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/nature17623","article-title":"Astrocyte scar formation aids central nervous system axon regeneration","volume":"532","author":"Anderson","year":"2016","journal-title":"Nature"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1089\/scd.2012.0524","article-title":"Combining adult stem cells and olfactory ensheathing cells: The secretome effect","volume":"22","author":"Silva","year":"2013","journal-title":"Stem Cells Dev."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Assun\u00e7\u00e3o-Silva, R.C., Gomes, E.D., Sousa, N., Silva, N.A., and Salgado, A.J. (2015). Hydrogels and cell based therapies in spinal cord injury regeneration. Stem Cells Int., 2015.","DOI":"10.1155\/2015\/948040"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/0014-4886(85)90119-0","article-title":"Spinal cord contusion in the rat: Morphometric analyses of alterations in the spinal cord","volume":"88","author":"Noble","year":"1985","journal-title":"Exp. Neurol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1016\/j.spinee.2016.04.013","article-title":"Combining neuroprotective agents: Effect of riluzole and magnesium in a rat model of thoracic spinal cord injury","volume":"16","author":"Vasconcelos","year":"2016","journal-title":"Spine J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1006\/exnr.2000.7604","article-title":"Effects of interleukin-10 (IL-10) on pain behavior and gene expression following excitotoxic spinal cord injury in the rat","volume":"168","author":"Plunkett","year":"2001","journal-title":"Exp. Neurol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1093\/brain\/awp322","article-title":"Quantitative analysis of cellular inflammation after traumatic spinal cord injury: Evidence for a multiphasic inflammatory response in the acute to chronic environment","volume":"133","author":"Beck","year":"2010","journal-title":"Brain"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1089\/neu.1995.12.1","article-title":"A sensitive and reliable locomotor rating scale for open field testing in rats","volume":"12","author":"Basso","year":"1995","journal-title":"J. Neurotrauma"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Anderson, C.R., Ashwell, K.W.S., Collewijn, H., Conta, A., Harvey, A., Heise, C., Hodgetts, S., Holstege, G., Kayalioglu, G., and Keast, J.R. (2009). The spinal cord: A christopher and dana reeve foundation text and atlas. The Spinal Cord, Academic Press.","DOI":"10.1016\/B978-0-12-374247-6.50001-8"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/10\/4\/83\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:48:19Z","timestamp":1760208499000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/10\/4\/83"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10,24]]},"references-count":54,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["ph10040083"],"URL":"https:\/\/doi.org\/10.3390\/ph10040083","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,10,24]]}}}