{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T16:16:03Z","timestamp":1788970563966,"version":"build-2803163510"},"reference-count":66,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,23]],"date-time":"2020-04-23T00:00:00Z","timestamp":1587600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["17GRNT33460327"],"award-info":[{"award-number":["17GRNT33460327"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1 R01 AI100987\u201001A1"],"award-info":[{"award-number":["1 R01 AI100987\u201001A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007727","name":"Biodesign Institute, Arizona State University","doi-asserted-by":"publisher","award":["Start-Up"],"award-info":[{"award-number":["Start-Up"]}],"id":[{"id":"10.13039\/100007727","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010621","name":"Uniwersytet Medyczny w Lublinie","doi-asserted-by":"publisher","award":["Grant"],"award-info":[{"award-number":["Grant"]}],"id":[{"id":"10.13039\/501100010621","id-type":"DOI","asserted-by":"publisher"}]},{"name":"VPC NeuroPath Consulting, Inc.","award":["Grant"],"award-info":[{"award-number":["Grant"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Spinal cord injury (SCI) results in massive secondary damage characterized by a prolonged inflammation with phagocytic macrophage invasion and tissue destruction. In prior work, sustained subdural infusion of anti-inflammatory compounds reduced neurological deficits and reduced pro-inflammatory cell invasion at the site of injury leading to improved outcomes. We hypothesized that implantation of a hydrogel loaded with an immune modulating biologic drug, Serp-1, for sustained delivery after crush-induced SCI would have an effective anti-inflammatory and neuroprotective effect. Rats with dorsal column SCI crush injury, implanted with physical chitosan-collagen hydrogels (CCH) had severe granulomatous infiltration at the site of the dorsal column injury, which accumulated excess edema at 28 days post-surgery. More pronounced neuroprotective changes were observed with high dose (100 \u00b5g\/50 \u00b5L) Serp-1 CCH implanted rats, but not with low dose (10 \u00b5g\/50 \u00b5L) Serp-1 CCH. Rats treated with Serp-1 CCH implants also had improved motor function up to 20 days with recovery of neurological deficits attributed to inhibition of inflammation-associated tissue damage. In contrast, prolonged low dose Serp-1 infusion with chitosan did not improve recovery. Intralesional implantation of hydrogel for sustained delivery of the Serp-1 immune modulating biologic offers a neuroprotective treatment of acute SCI.<\/jats:p>","DOI":"10.3390\/jcm9041221","type":"journal-article","created":{"date-parts":[[2020,4,23]],"date-time":"2020-04-23T10:46:22Z","timestamp":1587638782000},"page":"1221","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Local Serpin Treatment via Chitosan-Collagen Hydrogel after Spinal Cord Injury Reduces Tissue Damage and Improves Neurologic Function"],"prefix":"10.3390","volume":"9","author":[{"given":"Jacek M.","family":"Kwiecien","sequence":"first","affiliation":[{"name":"Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8S4L8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Personalized Diagnostics and Center for Immunotherapy, Vaccines and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4133-474X","authenticated-orcid":false,"given":"Jordan R.","family":"Yaron","sequence":"additional","affiliation":[{"name":"Center for Personalized Diagnostics and Center for Immunotherapy, Vaccines and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren N.","family":"Schutz","sequence":"additional","affiliation":[{"name":"Center for Personalized Diagnostics and Center for Immunotherapy, Vaccines and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian J.","family":"Kwiecien-Delaney","sequence":"additional","affiliation":[{"name":"Faculty of Science, McMaster University, Hamilton, ON L8S4L8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enkidia A.","family":"Awo","sequence":"additional","affiliation":[{"name":"Center for Personalized Diagnostics and Center for Immunotherapy, Vaccines and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Burgin","sequence":"additional","affiliation":[{"name":"Center for Personalized Diagnostics and Center for Immunotherapy, Vaccines and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0449-2375","authenticated-orcid":false,"given":"Wojciech","family":"Dabrowski","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology and Intensive Therapy, Medical University of Lublin, 20-400 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra R.","family":"Lucas","sequence":"additional","affiliation":[{"name":"Center for Personalized Diagnostics and Center for Immunotherapy, Vaccines and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/S1474-4422(18)30415-0","article-title":"Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990\u20132016: A systematic analysis for the Global Burden of Disease Study 2016","volume":"18","author":"James","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3879","DOI":"10.1038\/s41467-019-11707-7","article-title":"Moving beyond the glial scar for spinal cord repair","volume":"10","author":"Bradbury","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Kwiecien, J.M., Dabrowski, W., D\u0105browska-Bouta, B., Sulkowski, G., Oakden, W., Kwiecien-Delaney, C.J., Yaron, J.R., Zhang, L., Schutz, L., and Marzec-Kotarska, B. (2020). Prolonged inflammation leads to ongoing damage after spinal cord injury. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0226584"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1089\/neu.2014.3429","article-title":"Modulating inflammatory cell responses to spinal cord injury: All in good time","volume":"31","author":"Bowes","year":"2014","journal-title":"J. Neurotrauma"},{"key":"ref_5","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_6","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s11940-011-0162-5","article-title":"Acute Treatment Options for Spinal Cord Injury","volume":"14","author":"Markandaya","year":"2012","journal-title":"Curr. Treat. Options Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s00383-011-3012-3","article-title":"A review: The role of high dose methylprednisolone in spinal cord trauma in children","volume":"28","author":"Pettiford","year":"2012","journal-title":"Pediatr. Surg. Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1097\/BRS.0b013e31829ef226","article-title":"Spinal Injuries in United States Military Personnel Deployed to Iraq and Afghanistan: an epidemiological investigation involving 7877 combat casualties from 2005 to 2009","volume":"38","author":"Schoenfeld","year":"2013","journal-title":"Spine"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s12028-018-0537-5","article-title":"Current Topics in the Management of Acute Traumatic Spinal Cord Injury","volume":"30","author":"Shank","year":"2019","journal-title":"Neurocrit. Care"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Ahuja, C.S., Martin, A.R., and Fehlings, M. (2016). Recent advances in managing a spinal cord injury secondary to trauma. F1000Research, 5.","DOI":"10.12688\/f1000research.7586.1"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Guizar-Sahagun, G., Martinez-Cruz, A., Franco-Bourland, R.E., Cruz-Garc\u00eda, E., Corona-Juarez, A., Diaz-Ruiz, A., Grijalva, I., Reyes-Alva, H.J., and Madrazo, I. (2017). Creation of an intramedullary cavity by hemorrhagic necrosis removal 24 h after spinal cord contusion in rats for eventual intralesional implantation of restorative materials. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0176105"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"41","DOI":"10.5114\/fn.2015.49973","article-title":"Subdural infusion of dexamethasone inhibits leukomyelitis after acute spinal cord injury in a rat model","volume":"1","author":"Kwiecien","year":"2015","journal-title":"Folia Neuropathol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"41","DOI":"10.5114\/fn.2019.83830","article-title":"Myxoma virus derived immune modulating proteins, M-T7 and Serp-1, reduce early inflammation after spinal cord injury in the rat model","volume":"57","author":"Kwiecien","year":"2019","journal-title":"Folia Neuropathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.spinee.2005.11.001","article-title":"Methylprednisolone treatment in acute spinal cord injury: The myth challenged through a structured analysis of published literature","volume":"6","author":"Sayer","year":"2006","journal-title":"Spine J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1089\/neu.2015.4192","article-title":"Methylprednisolone for the treatment of patients with acute spinal cord injuries: A systematic review and meta-analysis","volume":"33","author":"Evaniew","year":"2016","journal-title":"J. Neurotrauma"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1227\/NEU.0b013e31827765c6","article-title":"Pharmacological therapy for acute spinal cord injury","volume":"72","author":"Hurlbert","year":"2013","journal-title":"Neurosurgery"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4658","DOI":"10.1523\/JNEUROSCI.0498-17.2017","article-title":"Insights into the dual role of inflammation after spinal cord injury","volume":"37","author":"Rust","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.pjnns.2015.10.006","article-title":"An in vivo model of anti-inflammatory activity of subdural dexamethasone following the spinal cord injury","volume":"50","author":"Kwiecien","year":"2016","journal-title":"Neurol. Neurochir. Pol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.biomaterials.2017.05.024","article-title":"Physical chitosan microhydrogels as scaffolds for spinal cord injury restoration and axon regeneration","volume":"138","author":"Chedly","year":"2017","journal-title":"Biomaterials"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"502","DOI":"10.4103\/1673-5374.228756","article-title":"Efficacy of chitosan and sodium alginate scaffolds for repair of spinal cord injury in rats","volume":"13","author":"Yao","year":"2018","journal-title":"Neural Regen. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"E5595","DOI":"10.1073\/pnas.1804735115","article-title":"NT3-chitosan enables de novo regeneration and functional recovery in monkeys after spinal cord injury","volume":"115","author":"Rao","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4114","DOI":"10.1128\/AAC.02594-12","article-title":"Myxomavirus-derived serpin prolongs survival and reduces inflammation and hemorrhage in an unrelated lethal mouse viral infection","volume":"57","author":"Chen","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2874","DOI":"10.1074\/jbc.M115.704841","article-title":"Reactive Center Loop (RCL) peptides derived from serpins display independent coagulation and immune modulating activities","volume":"291","author":"Ambadapadi","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1189\/jlb.0808506","article-title":"Myxoma viral serpin, Serp-1, inhibits human monocyte adhesion through regulation of actin-binding protein filamin B","volume":"85","author":"Viswanathan","year":"2009","journal-title":"J. Leukoc. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.clim.2014.05.003","article-title":"Suppression of collagen-induced arthritis with a serine proteinase inhibitor (serpin) derived from myxoma virus","volume":"153","author":"Brahn","year":"2014","journal-title":"Clin. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1161\/CIRCINTERVENTIONS.110.953885","article-title":"A randomized controlled, phase 2 trial of the viral serpin serp-1 in patients with acute coronary syndromes undergoing percutaneous coronary intervention","volume":"3","author":"Tardif","year":"2010","journal-title":"Circ. Cardiovasc. Interv."},{"key":"ref_27","first-page":"2957","article-title":"Neuroserpin restores autophagy and promotes functional recovery after acute spinal cord injury in rats","volume":"17","author":"Li","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.cyto.2013.10.005","article-title":"Defining the anti-inflammatory activity of a potent myxomaviral chemokine modulating protein, M-T7, through site directed mutagenesis","volume":"65","author":"Bartee","year":"2014","journal-title":"Cytokine"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3775","DOI":"10.1016\/j.biomaterials.2013.02.002","article-title":"Repair of the injured spinal cord by transplantation of neural stem cells in a hyaluronan-based hydrogel","volume":"34","author":"Mothe","year":"2013","journal-title":"Biomaterials"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"20151","DOI":"10.1073\/pnas.0709250104","article-title":"Chemokines and the pathophysiology of neuropathic pain","volume":"104","author":"White","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1021\/acs.biochem.7b01171","article-title":"Crystal Structure of Cleaved Serp-1, a Myxomavirus-Derived Immune Modulating Serpin: Structural Design of Serpin Reactive Center Loop Peptides with Improved Therapeutic Function","volume":"57","author":"Mahon","year":"2018","journal-title":"Biochemistry"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1007\/978-1-4939-8645-3_17","article-title":"Overview of serpins and their roles in biological systems","volume":"1826","author":"Lucas","year":"2018","journal-title":"Serpins"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/978-1-4939-8645-3_11","article-title":"Analysis of In Vivo Serpin Functions in Models of Inflammatory Vascular Disease","volume":"Volume 1826","author":"Lucas","year":"2018","journal-title":"Serpins"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Strickland, D.K., Muratoglu, S.C., and Antalis, T.M. (2011). Serpin-Enzyme Receptors: LDL Receptor-Related Protein 1, Elsevier. [1st ed.].","DOI":"10.1016\/B978-0-12-386471-0.00002-X"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6523","DOI":"10.1074\/jbc.271.11.6523","article-title":"Cellular internalization and degradation of antithrombin III-thrombin, heparin cofactor II-thrombin, and \u03b11-antitrypsin-trypsin complexes is mediated by the low density lipoprotein receptor-related protein","volume":"271","author":"Kounnas","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Gelderblom, M., Neumann, M., Ludewig, P., Bernreuther, C., Krasemann, S., Arunachalam, P., Gerloff, C., Glatzel, M., and Magnus, T. (2013). Deficiency in Serine Protease Inhibitor Neuroserpin Exacerbates Ischemic Brain Injury by Increased Postischemic Inflammation. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063118"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.nbd.2014.02.005","article-title":"tPA promotes ADAMTS-4-induced CSPG degradation, thereby enhancing neuroplasticity following spinal cord injury","volume":"66","author":"Lemarchant","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1089\/08977150360517173","article-title":"Decreased neural damage after spinal cord injury in tPA-deficient mice","volume":"20","author":"Abe","year":"2003","journal-title":"J. Neurotrauma"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/j.biomaterials.2008.10.063","article-title":"Repair of thoracic spinal cord injury by chitosan tube implantation in adult rats","volume":"30","author":"Li","year":"2009","journal-title":"Biomaterials"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/scrt480","article-title":"Repair of injured spinal cord using biomaterial scaffolds and stem cells","volume":"5","author":"Shrestha","year":"2014","journal-title":"Stem Cell Res. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"13354","DOI":"10.1073\/pnas.1510194112","article-title":"NT3-chitosan elicits robust endogenous neurogenesis to enable functional recovery after spinal cord injury","volume":"112","author":"Yang","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Zhang, L.Q., Yaron, J.R., Tafoya, A.M., Wallace, S.E., Kilbourne, J., Haydel, S., Rege, K., McFadden, G., and Lucas, A.R. (2019). A Virus-Derived Immune Modulating Serpin Accelerates Wound Closure with Improved Collagen Remodeling. J. Clin. Med., 8.","DOI":"10.3390\/jcm8101626"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1177\/0885328208090013","article-title":"RhBMP-2 microspheres-loaded chitosan\/collagen scaffold enhanced osseointegration: An experiment in dog","volume":"23","author":"Shi","year":"2009","journal-title":"J. Biomater. Appl."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"16369","DOI":"10.1523\/JNEUROSCI.1309-14.2014","article-title":"Entrapment via Synaptic-Like Connections between NG2 Proteoglycan+ Cells and Dystrophic Axons in the Lesion Plays a Role in Regeneration Failure after Spinal Cord Injury","volume":"34","author":"Filous","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/978-1-4939-8645-3_15","article-title":"Methods for Assessing Serpins as Neuroprotective Therapeutics","volume":"1826","author":"Lucas","year":"2018","journal-title":"Serpins"},{"key":"ref_46","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_47","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.brainres.2004.03.062","article-title":"Spontaneous and induced aberrant sprouting at the site of injury is irrelevant to motor function outcome in rats with spinal cord injury","volume":"1013","author":"Grijalva","year":"2004","journal-title":"Brain Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1089\/089771504323004548","article-title":"Behavioral Testing after Spinal Cord Injury: Congruities, Complexities, and Controversies","volume":"21","author":"Basso","year":"2004","journal-title":"J. Neurotrauma"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"49","DOI":"10.2174\/1871524915666150819104114","article-title":"Combined Strategy for a Reliable Evaluation of Spinal Cord Injury Using an in vivo Model","volume":"18","author":"Gomez","year":"2018","journal-title":"Cent. Nerv. Syst. Agents Med. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"189","DOI":"10.5114\/fn.2013.37703","article-title":"Cellular mechanisms of white matter regeneration in an adult dysmyelinated rat model","volume":"51","author":"Kwiecien","year":"2013","journal-title":"Folia Neuropathol."},{"key":"ref_51","unstructured":"Berhardt, L. (2016). Tissue reaction to acellular implants in the acute spinal cord injury in the dysmyelinated rat. Advances in Medicine and Biology, Nova Science Publishers, Inc."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1089\/neu.2013.3037","article-title":"Neuroprotective effects of perflurocarbon (oxycyte) after contusive spinal cord injury","volume":"31","author":"Yacoub","year":"2014","journal-title":"J. Neurotrauma"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"L\u00fc, H.-Z., Wang, Y.-X., Zhou, J.-S., Wang, F.-C., and Hu, J.-G. (2010). Cyclosporin A increases recovery after spinal cord injury but does not improve myelination by oligodendrocyte progenitor cell transplantation. BMC Neurosci., 11.","DOI":"10.1186\/1471-2202-11-127"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Sperling, L.E., Pires Reis, K., Nicola, F., Euzebio Teixeira, C., Gulielmin Did\u00f3, G., Garrido dos Santos, M., Konrath, E., Netto, C.A., and Pranke, P. (2019). Galantamine improves functional recovery and reduces lesion size in a rat model of spinal cord injury. Brain Res., 1724.","DOI":"10.1016\/j.brainres.2019.146424"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3136","DOI":"10.1172\/JCI91301","article-title":"Astrocytic tight junctions control inflammatory CNS lesion pathogenesis","volume":"127","author":"Horng","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"12870","DOI":"10.1523\/JNEUROSCI.2121-13.2013","article-title":"Glial scar borders are formed by newly proliferated, elongated astrocytes that interact to corral inflammatory and fibrotic cells via STAT3-dependent mechanisms after spinal cord injury","volume":"33","author":"Wanner","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_57","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_58","doi-asserted-by":"crossref","first-page":"2587","DOI":"10.1016\/j.matpr.2019.10.091","article-title":"Preparation and characterization of biodegradable collagen\u2014Chitosan scaffolds","volume":"19","year":"2019","journal-title":"Mater. Today Proc."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s10856-018-6033-9","article-title":"Differential degradation rate and underlying mechanism of a collagen\/chitosan complex in subcutis, spinal cord and brain tissues of rat","volume":"29","author":"Fu","year":"2018","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2269","DOI":"10.1097\/BRS.0b013e3181831f7e","article-title":"Neuroprotective effects of caspase-3 inhibition on functional recovery and tissue sparing after acute spinal cord injury","volume":"33","author":"Citron","year":"2008","journal-title":"Spine"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1160\/TH05-07-0492","article-title":"Myxoma viral serpin, Serp-1, a unique interceptor of coagulation and innate immune pathways","volume":"95","author":"Viswanathan","year":"2006","journal-title":"Thromb. Haemost."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"6296","DOI":"10.1073\/pnas.95.11.6296","article-title":"Posttranscriptional regulation of urokinase plasminogen activator receptor messenger RNA levels by leukocyte integrin engagement","volume":"95","author":"Wang","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1046\/j.0305-1846.2000.287.x","article-title":"Lesion-associated accumulation of uPAR\/CD87 expressing infiltrating granulocytes, activated microglial cells\/macrophages and upregulation by endothelial cells following TBI and FCI in humans","volume":"26","author":"Beschorner","year":"2000","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/cddis.2012.106","article-title":"Adoptive transfer of Th1-conditioned lymphocytes promotes axonal remodeling and functional recovery after spinal cord injury","volume":"3","author":"Ishii","year":"2012","journal-title":"Cell Death Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.neuron.2013.12.034","article-title":"Reactive gliosis and the multicellular response to CNS damage and disease","volume":"81","author":"Burda","year":"2014","journal-title":"Neuron"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1242\/dmm.025833","article-title":"Rat models of spinal cord injury: From pathology to potential therapies","volume":"9","author":"Kjell","year":"2016","journal-title":"DMM Dis. Model. 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