{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:38:11Z","timestamp":1791999491880,"version":"4.4.0"},"reference-count":61,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:00:00Z","timestamp":1741737600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2019s Seventh Framework Program FP7","award":["607962"],"award-info":[{"award-number":["607962"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Blood\u2013brain barrier dysfunction (BBB) is a primary characteristic of experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis (MS). We have previously shown that blocking microglial proliferation using GW2580, a selective inhibitor of CSF1R (Colony stimulating factor 1 receptor), reduced disease progression and severity and prevented the relapse phase. However, whether this was due to effects of GW2580 on the functional integrity of the BBB was not determined. Therefore, here, we examine BBB properties in rats during EAE under GW2580 treatment. Our data suggest that blocking early microglial proliferation through selective targeting of CSF1R signaling has a therapeutic effect in EAE by protecting BBB integrity and reducing peripheral immune cell infiltration. Taken together, our results identify a novel mechanism underlying the effects of GW2580, which could offer a novel therapy for MS.<\/jats:p>","DOI":"10.3390\/cells14060414","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T04:55:44Z","timestamp":1741755344000},"page":"414","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Pharmacological Inhibition of Microglial Proliferation Supports Blood\u2013Brain Barrier Integrity in Experimental Autoimmune Encephalomyelitis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3729-2521","authenticated-orcid":false,"given":"Nozha","family":"Borjini","sequence":"first","affiliation":[{"name":"Research & Development, Chiesi Farmaceutici S.p.A, via Palermo 26\/A, 43100 Parma, Italy"},{"name":"IRET Foundation, via Tolara di Sopra 41\/E, Ozzano Emilia, 40064 Bologna, Italy"},{"name":"Department de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica, Instituto de Biomedicina de Sevilla (IBiS, Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla), 41013 Sevilla, Spain"},{"name":"Facultad de Medicina and CIBERNED ISCIII, 41013 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1237-5275","authenticated-orcid":false,"given":"Mercedes","family":"Fernandez","sequence":"additional","affiliation":[{"name":"IRET Foundation, via Tolara di Sopra 41\/E, Ozzano Emilia, 40064 Bologna, Italy"},{"name":"Health Science and Technologies Interdepartmental Center for Industrial Research (HST-ICIR), University of Bologna, via Tolara di Sopra 41\/E, Ozzano Emilia, 40064 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana","family":"Giardino","sequence":"additional","affiliation":[{"name":"Health Science and Technologies Interdepartmental Center for Industrial Research (HST-ICIR), University of Bologna, via Tolara di Sopra 41\/E, Ozzano Emilia, 40064 Bologna, Italy"},{"name":"Department of Veterinary Medical Sciences, University of Bologna, via Tolara di Sopra 50, Ozzano Emilia (BO), 40064 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia","family":"Sorokin","sequence":"additional","affiliation":[{"name":"Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, 48149 Muenster, Germany"},{"name":"Cells-in-Motion Interfaculty Centre (CIMIC), University of Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4426-8477","authenticated-orcid":false,"given":"Laura","family":"Calz\u00e0","sequence":"additional","affiliation":[{"name":"Health Science and Technologies Interdepartmental Center for Industrial Research (HST-ICIR), University of Bologna, via Tolara di Sopra 41\/E, Ozzano Emilia, 40064 Bologna, Italy"},{"name":"Department of Pharmacy and Biotechnology, University of Bologna, via Tolara di Sopra 41\/E, Ozzano Emilia, 40064 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S1471-4914(00)01909-2","article-title":"Heterogeneity of Multiple Sclerosis Pathogenesis: Implications for Diagnosis and Therapy","volume":"7","author":"Lassmann","year":"2001","journal-title":"Trends Mol. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1093\/brain\/113.5.1477","article-title":"Breakdown of the Blood-Brain Barrier Precedes Symptoms and Other MRI Signs of New Lesions in Multiple Sclerosis. Pathogenetic and Clinical Implications","volume":"113","author":"Kermode","year":"1990","journal-title":"Brain J. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1093\/brain\/114.1.557","article-title":"Blood-Brain Barrier Damage in Acute Multiple Sclerosis Plaques. An Immunocytological Study","volume":"114","author":"Gay","year":"1991","journal-title":"Brain J. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1093\/brain\/120.8.1461","article-title":"The Application of Multifactorial Cluster Analysis in the Staging of Plaques in Early Multiple Sclerosis. Identification and Characterization of the Primary Demyelinating Lesion","volume":"120","author":"Gay","year":"1997","journal-title":"Brain J. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1056\/NEJM199801293380502","article-title":"Axonal Transection in the Lesions of Multiple Sclerosis","volume":"338","author":"Trapp","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1074\/jbc.R116.760215","article-title":"The Translational Significance of the Neurovascular Unit","volume":"292","author":"McConnell","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.neuroscience.2018.06.046","article-title":"Microglia in the Neurovascular Unit: Blood\u2013Brain Barrier\u2013Microglia Interactions After Central Nervous System Disorders","volume":"405","author":"Thurgur","year":"2019","journal-title":"Neuroscience"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1084\/jem.20051342","article-title":"Dystroglycan Is Selectively Cleaved at the Parenchymal Basement Membrane at Sites of Leukocyte Extravasation in Experimental Autoimmune Encephalomyelitis","volume":"203","author":"Agrawal","year":"2006","journal-title":"J. Exp. Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Lakhan, S.E., Kirchgessner, A., Tepper, D., and Leonard, A. (2013). Matrix Metalloproteinases and Blood-Brain Barrier Disruption in Acute Ischemic Stroke. Front. Neurol., 4.","DOI":"10.3389\/fneur.2013.00032"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1016\/j.celrep.2015.01.037","article-title":"Focal MMP-2 and MMP-9 Activity at the Blood-Brain Barrier Promotes Chemokine-Induced Leukocyte Migration","volume":"10","author":"Song","year":"2015","journal-title":"Cell Rep."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Zhang, S., Kan, Q.-C., Xu, Y., Zhang, G.-X., and Zhu, L. (2013). Inhibitory Effect of Matrine on Blood-Brain Barrier Disruption for the Treatment of Experimental Autoimmune Encephalomyelitis. Mediators Inflamm., 2013.","DOI":"10.1155\/2013\/736085"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Lu, P., Takai, K., Weaver, V.M., and Werb, Z. (2011). Extracellular Matrix Degradation and Remodeling in Development and Disease. Cold Spring Harb. Perspect. Biol., 3.","DOI":"10.1101\/cshperspect.a005058"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"43503","DOI":"10.1074\/jbc.M107736200","article-title":"Matrix Metalloproteinase Activity Inactivates the CXC Chemokine Stromal Cell-Derived Factor-1","volume":"276","author":"McQuibban","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1083\/jcb.201412147","article-title":"Brain Barriers: Crosstalk between Complex Tight Junctions and Adherens Junctions","volume":"209","author":"Tietz","year":"2015","journal-title":"J Cell Biol"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.matbio.2017.11.007","article-title":"The Gelatinases, MMP-2 and MMP-9, as Fine Tuners of Neuroinflammatory Processes","volume":"75\u201376","author":"Hannocks","year":"2019","journal-title":"Matrix Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e20211071","DOI":"10.1084\/jem.20211071","article-title":"Microglia Modulate Blood Flow, Neurovascular Coupling, and Hypoperfusion via Purinergic Actions","volume":"219","author":"Fekete","year":"2022","journal-title":"J. Exp. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1126\/science.aax6752","article-title":"Microglia Monitor and Protect Neuronal Function through Specialized Somatic Purinergic Junctions","volume":"367","author":"Fekete","year":"2020","journal-title":"Science"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1007\/s00429-019-01834-8","article-title":"Microglia Contribute to the Glia Limitans around Arteries, Capillaries and Veins under Physiological Conditions, in a Model of Neuroinflammation and in Human Brain Tissue","volume":"224","author":"Joost","year":"2019","journal-title":"Brain Struct. Funct."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Peplow, P.V., Martinez, B., and Gennarelli, T.A. (2022). Activation of Microglia and Macrophages in Neurodegenerative Diseases. Neurodegenerative Diseases Biomarkers: Towards Translating Research to Clinical Practice, Springer. Neuromethods.","DOI":"10.1007\/978-1-0716-1712-0"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13024-018-0244-x","article-title":"Early Long-Term Administration of the CSF1R Inhibitor PLX3397 Ablates Microglia and Reduces Accumulation of Intraneuronal Amyloid, Neuritic Plaque Deposition and Pre-Fibrillar Oligomers in 5XFAD Mouse Model of Alzheimer\u2019s Disease","volume":"13","author":"Sosna","year":"2018","journal-title":"Mol. Neurodegener."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1093\/brain\/aww016","article-title":"Eliminating Microglia in Alzheimer\u2019s Mice Prevents Neuronal Loss without Modulating Amyloid-\u03b2 Pathology","volume":"139","author":"Spangenberg","year":"2016","journal-title":"Brain J. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Tarale, P., and Alam, M.M. (2022). Colony-Stimulating Factor 1 Receptor Signaling in the Central Nervous System and the Potential of Its Pharmacological Inhibitors to Halt the Progression of Neurological Disorders. Inflammopharmacology.","DOI":"10.1007\/s10787-022-00958-4"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.expneurol.2018.05.021","article-title":"Csf1R Inhibition Attenuates Experimental Autoimmune Encephalomyelitis and Promotes Recovery","volume":"307","author":"Nissen","year":"2018","journal-title":"Exp. Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3336","DOI":"10.1096\/fj.201700833RR","article-title":"Depletion of Microglia Augments the Dopaminergic Neurotoxicity of MPTP","volume":"32","author":"Yang","year":"2018","journal-title":"FASEB J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1073\/pnas.1520398113","article-title":"Purinergic Receptor P2RY12-Dependent Microglial Closure of the Injured Blood\u2013Brain Barrier","volume":"113","author":"Lou","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"16078","DOI":"10.1073\/pnas.0502000102","article-title":"Inhibition of Colony-Stimulating-Factor-1 Signaling in Vivo with the Orally Bioavailable cFMS Kinase Inhibitor GW2580","volume":"102","author":"Conway","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1096\/fj.201900567RR","article-title":"Pharmacological Inhibition of CSF1R by GW2580 Reduces Microglial Proliferation and Is Protective against Neuroinflammation and Dopaminergic Neurodegeneration","volume":"34","author":"Neal","year":"2020","journal-title":"FASEB J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.1523\/JNEUROSCI.4440-12.2013","article-title":"Regulation of Microglial Proliferation during Chronic Neurodegeneration","volume":"33","author":"Fransen","year":"2013","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.bbi.2015.11.001","article-title":"Microglia Regulate Hippocampal Neurogenesis during Chronic Neurodegeneration","volume":"55","author":"Rinchon","year":"2016","journal-title":"Brain. Behav. Immun."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez-Muriana, A., Mancuso, R., Francos-Quijorna, I., Olmos-Alonso, A., Osta, R., Perry, V.H., Navarro, X., Gomez-Nicola, D., and L\u00f3pez-Vales, R. (2016). CSF1R Blockade Slows the Progression of Amyotrophic Lateral Sclerosis by Reducing Microgliosis and Invasion of Macrophages into Peripheral Nerves. Sci. Rep., 6.","DOI":"10.1038\/srep25663"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1093\/brain\/awv379","article-title":"Pharmacological Targeting of CSF1R Inhibits Microglial Proliferation and Prevents the Progression of Alzheimer\u2019s-like Pathology","volume":"139","author":"Schetters","year":"2016","journal-title":"Brain"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1007\/s10875-011-9579-6","article-title":"Tyrosine Kinase Inhibitors Ameliorate Autoimmune Encephalomyelitis in a Mouse Model of Multiple Sclerosis","volume":"31","author":"Crespo","year":"2011","journal-title":"J. Clin. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1186\/s12974-016-0757-6","article-title":"Cytokine and Chemokine Alterations in Tissue, CSF, and Plasma in Early Presymptomatic Phase of Experimental Allergic Encephalomyelitis (EAE), in a Rat Model of Multiple Sclerosis","volume":"13","author":"Borjini","year":"2016","journal-title":"J. Neuroinflammation"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1177\/026119290203002S36","article-title":"Directive 86\/609\/EEC on the Protection of Animals Used for Experimental and Other Scientific Purposes","volume":"30","author":"Louhimies","year":"2002","journal-title":"Altern. Lab. Anim. ATLA"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Leblond, A.-L., Klinkert, K., Martin, K., Turner, E.C., Kumar, A.H., Browne, T., and Caplice, N.M. (2015). Systemic and Cardiac Depletion of M2 Macrophage through CSF-1R Signaling Inhibition Alters Cardiac Function Post Myocardial Infarction. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0137515"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1002\/nau.24896","article-title":"The Preventive Effects of Colony-Stimulating Factor 1 Receptor (CSF-1R) Inhibition on Bladder Outlet Obstruction Induced Remodeling","volume":"41","author":"Wang","year":"2022","journal-title":"Neurourol. Urodyn."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3258","DOI":"10.1073\/pnas.052704499","article-title":"Thyroid Hormone Activates Oligodendrocyte Precursors and Increases a Myelin-Forming Protein and NGF Content in the Spinal Cord during Experimental Allergic Encephalomyelitis","volume":"99","author":"Calza","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"W90","DOI":"10.1093\/nar\/gkw377","article-title":"Enrichr: A Comprehensive Gene Set Enrichment Analysis Web Server 2016 Update","volume":"44","author":"Kuleshov","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1083\/jcb.153.5.933","article-title":"Endothelial Cell Laminin Isoforms, Laminins 8 and 10, Play Decisive Roles in T Cell Recruitment across the Blood-Brain Barrier in Experimental Autoimmune Encephalomyelitis","volume":"153","author":"Sixt","year":"2001","journal-title":"J. Cell Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1093\/brain\/awt093","article-title":"Extracellular Matrix Metalloproteinase Inducer Shows Active Perivascular Cuffs in Multiple Sclerosis","volume":"136","author":"Agrawal","year":"2013","journal-title":"Brain"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/nm.1957","article-title":"Endothelial Basement Membrane Laminin Alpha5 Selectively Inhibits T Lymphocyte Extravasation into the Brain","volume":"15","author":"Wu","year":"2009","journal-title":"Nat. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1016\/S0140-6736(02)08220-X","article-title":"Multiple Sclerosis","volume":"359","author":"Compston","year":"2002","journal-title":"Lancet Lond. Engl."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1056\/NEJMra052130","article-title":"Multiple Sclerosis--the Plaque and Its Pathogenesis","volume":"354","author":"Frohman","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/nrneurol.2012.168","article-title":"Progressive Multiple Sclerosis: Pathology and Pathogenesis","volume":"8","author":"Lassmann","year":"2012","journal-title":"Nat. Rev. Neurol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1146\/annurev.neuro.30.051606.094313","article-title":"Multiple Sclerosis: An Immune or Neurodegenerative Disorder?","volume":"31","author":"Trapp","year":"2008","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_46","unstructured":"Zigmond, M.J., Coyle, J.T., and Rowland, L.P. (2014). Neurobiology of Brain Disorders: Biological Basis of Neurological and Psychiatric Disorders, Elsevier."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Erblich, B., Zhu, L., Etgen, A.M., Dobrenis, K., and Pollard, J.W. (2011). Absence of Colony Stimulation Factor-1 Receptor Results in Loss of Microglia, Disrupted Brain Development and Olfactory Deficits. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0026317"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1126\/science.1194637","article-title":"Fate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages","volume":"330","author":"Ginhoux","year":"2010","journal-title":"Science"},{"key":"ref_49","first-page":"1921","article-title":"A CSF-1 Receptor Kinase Inhibitor Targets Effector Functions and Inhibits pro-Inflammatory Cytokine Production from Murine Macrophage Populations","volume":"20","author":"Irvine","year":"2006","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Adzemovic, M.V., Adzemovic, M.Z., Zeitelhofer, M., Eriksson, U., Olsson, T., and Nilsson, I. (2013). Imatinib Ameliorates Neuroinflammation in a Rat Model of Multiple Sclerosis by Enhancing Blood-Brain Barrier Integrity and by Modulating the Peripheral Immune Response. PLoS ONE, 8.","DOI":"10.1371\/annotation\/dd60f248-ca3f-4824-a3b4-c07aefb1c7c3"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.it.2005.07.004","article-title":"The Ins and Outs of T-Lymphocyte Trafficking to the CNS: Anatomical Sites and Molecular Mechanisms","volume":"26","author":"Engelhardt","year":"2005","journal-title":"Trends Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1038\/nri2852","article-title":"The Impact of the Extracellular Matrix on Inflammation","volume":"10","author":"Sorokin","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3770","DOI":"10.1016\/j.febslet.2011.04.066","article-title":"How Do Immune Cells Overcome the Blood\u2013Brain Barrier in Multiple Sclerosis?","volume":"585","author":"Larochelle","year":"2011","journal-title":"FEBS Lett."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1002\/1521-4141(200208)32:8<2133::AID-IMMU2133>3.0.CO;2-W","article-title":"Functional Expression of the Lymphoid Chemokines CCL19 (ELC) and CCL 21 (SLC) at the Blood-Brain Barrier Suggests Their Involvement in G-Protein-Dependent Lymphocyte Recruitment into the Central Nervous System during Experimental Autoimmune Encephalomyelitis","volume":"32","author":"Alt","year":"2002","journal-title":"Eur. J. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Dorovini-Zis, K. (2015). The Blood-Brain Barrier in Health and Disease, Volume One: Morphology, Biology and Immune Function, CRC Press.","DOI":"10.1201\/b18606"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/nrn2995","article-title":"Engaging Neuroscience to Advance Translational Research in Brain Barrier Biology","volume":"12","author":"Neuwelt","year":"2011","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"10523","DOI":"10.1038\/ncomms10523","article-title":"Rapid Endothelial Cytoskeletal Reorganization Enables Early Blood\u2013Brain Barrier Disruption and Long-Term Ischaemic Reperfusion Brain Injury","volume":"7","author":"Shi","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"133","DOI":"10.4062\/biomolther.2012.20.2.133","article-title":"Matrix Metalloproteinases, New Insights into the Understanding of Neurodegenerative Disorders","volume":"20","author":"Kim","year":"2012","journal-title":"Biomol. Ther."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3739","DOI":"10.1046\/j.1432-1033.2003.03760.x","article-title":"Gelatinase B\/MMP-9 and Neutrophil Collagenase\/MMP-8 Process the Chemokines Human GCP-2\/CXCL6, ENA-78\/CXCL5 and Mouse GCP-2\/LIX and Modulate Their Physiological Activities","volume":"270","author":"Wuyts","year":"2003","journal-title":"Eur. J. Biochem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2673","DOI":"10.1182\/blood.V96.8.2673","article-title":"Neutrophil Gelatinase B Potentiates Interleukin-8 Tenfold by Aminoterminal Processing, Whereas It Degrades CTAP-III, PF-4, and GRO-Alpha and Leaves RANTES and MCP-2 Intact","volume":"96","author":"Proost","year":"2000","journal-title":"Blood"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1124\/jpet.107.129429","article-title":"Effects of the cFMS Kinase Inhibitor 5-(3-Methoxy-4-((4-Methoxybenzyl)Oxy)Benzyl)Pyrimidine-2,4-Diamine (GW2580) in Normal and Arthritic Rats","volume":"326","author":"Conway","year":"2008","journal-title":"J. Pharmacol. Exp. Ther."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/6\/414\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:51:03Z","timestamp":1760028663000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/6\/414"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,12]]},"references-count":61,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["cells14060414"],"URL":"https:\/\/doi.org\/10.3390\/cells14060414","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,12]]}}}