{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T01:05:56Z","timestamp":1784250356714,"version":"3.55.0"},"reference-count":80,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,24]],"date-time":"2026-05-24T00:00:00Z","timestamp":1779580800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":54,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100002383","name":"King Saud University","doi-asserted-by":"publisher","award":["The work was supported by the Researchers Supporting Project Number (ORF-2026-709), King Saud University."],"award-info":[{"award-number":["The work was supported by the Researchers Supporting Project Number (ORF-2026-709), King Saud University."]}],"id":[{"id":"10.13039\/501100002383","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Mol Neurobiol"],"DOI":"10.1007\/s10571-026-01751-5","type":"journal-article","created":{"date-parts":[[2026,5,24]],"date-time":"2026-05-24T03:35:17Z","timestamp":1779593717000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["S3I-201, a STAT3 Inhibitor, Inhibits Proinflammatory Mediator Signalling in CD19 and CD45R\/B220 Cells in a Mouse Model of Multiple Sclerosis"],"prefix":"10.1007","volume":"46","author":[{"given":"Abdulaziz M. S.","family":"Alsaad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Nadeem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabry M.","family":"Attia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mushtaq A.","family":"Ansari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saleh A.","family":"Bakheet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Majed Ali","family":"Algonaiah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haneen A.","family":"Al-Mazroua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hatun A.","family":"Alomar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wedad S.","family":"Sarawi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed M.","family":"Almutairi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah A.","family":"Aldossari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quaiser","family":"Saquib","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norah K.","family":"Algarzae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed A.","family":"Mahmoud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa H.","family":"Hussein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheikh F.","family":"Ahmad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,24]]},"reference":[{"issue":"SII","key":"1751_CR1","first-page":"235","volume":"21","author":"M Agius","year":"2015","unstructured":"Agius M, Klodowska-Duda G, Maciejowski M et al (2015) Safety and tolerability of MEDI-551 in patients with relapsing forms of multiple sclerosis: results from a phase 1 randomised, placebo-controlled, escalating intravenous and subcutaneous dose study. Mult Scler J 21(SII):235\u2013236","journal-title":"Mult Scler J"},{"key":"1751_CR2","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.cellsig.2018.09.006","volume":"52","author":"SF Ahmad","year":"2018","unstructured":"Ahmad SF, Ansari MA, Nadeem A, Bakheet SA, Alshammari MA, Khan MR, Alsaad AMS, Attia SM (2018) S3I-201, a selective Stat3 inhibitor, restores neuroimmune function through upregulation of Treg signaling in autistic BTBR T+ Itpr3tf\/J mice. Cell Signal 52:127\u2013136","journal-title":"Cell Signal"},{"key":"1751_CR3","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.brainresbull.2019.07.006","volume":"152","author":"SF Ahmad","year":"2019","unstructured":"Ahmad SF, Ansari MA, Nadeem A, Bakheet SA et al (2019) The Stat3 inhibitor, S3I-201, downregulates lymphocyte activation markers, chemokine receptors, and inflammatory cytokines in the BTBR T+ Itpr3tf\/J mouse model of autism. Brain Res Bull 152:27\u201334","journal-title":"Brain Res Bull"},{"key":"1751_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2023.104658","volume":"73","author":"SF Ahmad","year":"2023","unstructured":"Ahmad SF, Ansari MA, Nadeem A, Bakheet SA, Al-Mazroua HA, Alomar HA, Al-Hamamah MA, Attia SM (2023) S3I-201, a selective Stat3 inhibitor, ameliorates clinical symptoms in a mouse model of experimental autoimmune encephalomyelitis through the regulation of multiple intracellular signalling in Th1, Th17, and Treg cells. Mult Scler Relat Disord 73:104658","journal-title":"Mult Scler Relat Disord"},{"key":"1751_CR5","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1038\/nn.2887","volume":"14","author":"B Ajami","year":"2011","unstructured":"Ajami B, Bennett JL, Krieger C, McNagny KM, Rossi FM (2011) Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool. Nat Neurosci 14:1142\u20131150","journal-title":"Nat Neurosci"},{"issue":"7","key":"1751_CR6","doi-asserted-by":"publisher","first-page":"925","DOI":"10.3390\/pharmaceutics13070925","volume":"13","author":"K Alhazzani","year":"2021","unstructured":"Alhazzani K, Ahmad SF, Al-Harbi NO, Attia SM, Bakheet SA et al (2021) Pharmacological Inhibition of STAT3 by Stattic Ameliorates Clinical Symptoms and Reduces Autoinflammation in Myeloid, Lymphoid, and Neuronal Tissue Compartments in Relapsing-Remitting Model of Experimental Autoimmune Encephalomyelitis in SJL\/J Mice. Pharmaceutics 13(7):925","journal-title":"Pharmaceutics"},{"issue":"10","key":"1751_CR7","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.1177\/1352458514521887","volume":"20","author":"S Amor","year":"2014","unstructured":"Amor S, van der Star BJ, Bosca I, Raffel J, Gnanapavan S, Watchorn J, Kuhle J, Giovannoni G, Baker D, Malaspina A, Puentes F (2014) Neurofilament light antibodies in serum reflect response to natalizumab treatment in multiple sclerosis. Mult Scler 20(10):1355\u20131362","journal-title":"Mult Scler"},{"key":"1751_CR8","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2022.113997","volume":"351","author":"MA Ansari","year":"2022","unstructured":"Ansari MA, Nadeem A, Alshammari MA, Attia SM, Bakheet SA et al (2022) Cathepsin B inhibitor alleviates Th1, Th17, and Th22 transcription factor signaling dysregulation in experimental autoimmune encephalomyelitis. Exp Neurol 351:113997","journal-title":"Exp Neurol"},{"key":"1751_CR9","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1084\/jem.20111675","volume":"209","author":"TA Barr","year":"2012","unstructured":"Barr TA, Shen P, Brown S, Lampropoulou V, Roch T et al (2012) B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6-producing B cells. J Exp Med 209:1001\u20131010","journal-title":"J Exp Med"},{"key":"1751_CR10","doi-asserted-by":"publisher","first-page":"2322","DOI":"10.4049\/jimmunol.1100725","volume":"187","author":"R Bassil","year":"2011","unstructured":"Bassil R, Zhu B, Lahoud Y, Riella LV, Yagita H, Elyaman W, Khoury SJ (2011) Notch ligand delta-like 4 blockade alleviates experimental autoimmune encephalomyelitis by promoting regulatory T cell development. J Immunol 187:2322\u20132328","journal-title":"J Immunol"},{"key":"1751_CR11","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/570731","volume":"2013","author":"R Bassil","year":"2013","unstructured":"Bassil R, Orent W, Elyaman W (2013) Notch signaling and T-helper cells in EAE\/MS. Clin Dev Immunol 2013:570731","journal-title":"Clin Dev Immunol"},{"key":"1751_CR12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.999008","volume":"13","author":"CF Beesley","year":"2023","unstructured":"Beesley CF, Goldman NR, Taher TE, Denton CP, Abraham DJ, Mageed RA, Ong VH (2023) Dysregulated B cell function and disease pathogenesis in systemic sclerosis. Front Immunol 13:999008","journal-title":"Front Immunol"},{"issue":"7","key":"1751_CR13","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/s41582-021-00498-5","volume":"17","author":"MT Cencioni","year":"2021","unstructured":"Cencioni MT, Mattoscio M, Magliozzi R, Bar-Or A, Muraro PA (2021) B cells in multiple sclerosis - from targeted depletion to immune reconstitution therapies. Nat Rev Neurol 17(7):399\u2013414","journal-title":"Nat Rev Neurol"},{"issue":"Suppl. 16","key":"1751_CR14","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.88.16_supplement.P1.391","volume":"88","author":"CS Constantinescu","year":"2017","unstructured":"Constantinescu CS, Aram J, Tanasescu R, Morandi E, Frakich N, Spendlove I, Gran B (2017) Expression and regulation of GMCSF in immune cell subsets in MS (P1.391). Neurology 88(Suppl. 16):P1.391","journal-title":"Neurology"},{"key":"1751_CR15","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/S0165-5728(02)00464-2","volume":"136","author":"AI Danilov","year":"2003","unstructured":"Danilov AI, Andersson M, Bavand N, Wiklund NP, Olsson T, Brundin L (2003) Nitric oxide metabolite determinations reveal continuous inflammation in multiple sclerosis. J Neuroimmunol 136:112\u2013118","journal-title":"J Neuroimmunol"},{"key":"1751_CR16","doi-asserted-by":"publisher","first-page":"5","DOI":"10.3389\/fnmol.2015.00005","volume":"8","author":"DJ Devier","year":"2015","unstructured":"Devier DJ, Lovera JF, Lukiw WJ (2015) Increase in NF-\u03baB-sensitive miRNA-146a and miRNA-155 in multiple sclerosis (MS) and pro-inflammatory neurodegeneration. Front Mol Neurosci 8:5","journal-title":"Front Mol Neurosci"},{"issue":"3","key":"1751_CR18","doi-asserted-by":"publisher","first-page":"966","DOI":"10.4049\/jimmunol.1701484","volume":"200","author":"PC Duncker","year":"2018","unstructured":"Duncker PC, Stoolman JS, Huber AK, Segal BM (2018) GM-CSF promotes chronic disability in experimental autoimmune encephalomyelitis by altering the composition of central nervous system-infiltrating cells, but is dispensable for disease induction. J Immunol 200(3):966\u2013973","journal-title":"J Immunol"},{"key":"1751_CR20","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/1742-2094-9-15","volume":"9","author":"G Ellrichmann","year":"2012","unstructured":"Ellrichmann G, Thone J, Lee DH, Rupec RA, Gold R, Linker RA (2012) Constitutive activity of NF-kappa B in myeloid cells drives pathogenicity of monocytes and macrophages during autoimmune neuroinflammation. J Neuroinflammation 9:15","journal-title":"J Neuroinflammation"},{"key":"1751_CR21","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1016\/j.immuni.2012.01.020","volume":"36","author":"W Elyaman","year":"2012","unstructured":"Elyaman W, Bassil R, Bradshaw EM, Orent W, Lahoud Y, Zhu B, Radtke F, Yagita H, Khoury SJ (2012) Notch receptors and Smad3 signaling cooperate in the induction of interleukin-9-producing T cells. Immunity 36:623\u2013634","journal-title":"Immunity"},{"key":"1751_CR22","doi-asserted-by":"publisher","first-page":"1254","DOI":"10.7150\/ijbs.4679","volume":"8","author":"M Erta","year":"2012","unstructured":"Erta M, Quintana A, Hidalgo J (2012) Interleukin-6, a major cytokine in the central nervous system. Int J Biol Sci 8:1254\u20131266","journal-title":"Int J Biol Sci"},{"issue":"2","key":"1751_CR23","doi-asserted-by":"publisher","first-page":"15","DOI":"10.3390\/brainsci6020015","volume":"6","author":"M Erta","year":"2016","unstructured":"Erta M, Giralt M, Jim\u00e9nez S, Molinero A, Comes G, Hidalgo J (2016) Astrocytic IL-6 influences the clinical symptoms of EAE in mice. Brain Sci 6(2):15","journal-title":"Brain Sci"},{"issue":"12","key":"1751_CR24","doi-asserted-by":"publisher","first-page":"2090","DOI":"10.1002\/eji.201646901","volume":"47","author":"M Fern\u00e1ndez","year":"2017","unstructured":"Fern\u00e1ndez M, Monsalve EM, L\u00f3pez-L\u00f3pez S, Ruiz-Garc\u00eda A et al (2017) Absence of Notch1 in murine myeloid cells attenuates the development of experimental autoimmune encephalomyelitis by affecting Th1 and Th17 priming. Eur J Immunol 47(12):2090\u20132100","journal-title":"Eur J Immunol"},{"key":"1751_CR25","first-page":"65","volume":"6","author":"A Finkelsztejn","year":"2014","unstructured":"Finkelsztejn A (2014) Multiple sclerosis: overview of disease-modifying agents. Perspect Med Chem 6:65\u201372","journal-title":"Perspect Med Chem"},{"key":"1751_CR26","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1002\/glia.22457","volume":"61","author":"M Giralt","year":"2013","unstructured":"Giralt M, Ramos R, Quintana A, Ferrer B, Erta M, Castro-Freire M et al (2013) Induction of atypical EAE mediated by transgenic production of IL-6 in astrocytes in the absence of systemic IL-6. Glia 61:587\u2013600","journal-title":"Glia"},{"key":"1751_CR27","doi-asserted-by":"publisher","DOI":"10.1126\/science.aal3222","author":"D Gosselin","year":"2017","unstructured":"Gosselin D, Skola D, Coufal NG, Holtman IR, Schlachetzki JCM, Sajti E et al (2017) An environment-dependent transcriptional network specifies human microglia identity. Science. https:\/\/doi.org\/10.1126\/science.aal3222","journal-title":"Science"},{"issue":"15","key":"1751_CR28","doi-asserted-by":"publisher","first-page":"1519","DOI":"10.1002\/glia.20553","volume":"55","author":"L Grandbarbe","year":"2007","unstructured":"Grandbarbe L, Michelucci A, Heurtaux T, Hemmer K, Morga E, Heuschling P (2007) Notch signaling modulates the activation of microglial cells. Glia 55(15):1519\u20131530","journal-title":"Glia"},{"issue":"4","key":"1751_CR29","doi-asserted-by":"publisher","first-page":"321","DOI":"10.17219\/acem\/185689","volume":"33","author":"FD Gregorio","year":"2024","unstructured":"Gregorio FD, Battaglia S (2024) The intricate brain-body interaction in psychiatric and neurological diseases. Adv Clin Exp Med 33(4):321\u2013326","journal-title":"Adv Clin Exp Med"},{"issue":"2","key":"1751_CR30","doi-asserted-by":"publisher","first-page":"e431","DOI":"10.1212\/NXI.0000000000000431","volume":"5","author":"T Guerrier","year":"2017","unstructured":"Guerrier T, Labalette M, Launay D, Lee-Chang C et al (2017) Proinflammatory B-cell profile in the early phases of MS predicts an active disease. Neurol Neuroimmunol Neuroinflamm 5(2):e431","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"1751_CR31","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.1016\/j.ajpath.2016.01.004","volume":"186","author":"W Hao","year":"2016","unstructured":"Hao W, Decker Y, Schnoder L, Schottek A, Li D, Menger MD, Fassbender K, Liu Y (2016) Deficiency of I\u03ba\u03b2 kinase \u03b2 in myeloid cells reduces severity of experimental autoimmune encephalomyelitis. Am J Pathol 186:1245\u20131257","journal-title":"Am J Pathol"},{"key":"1751_CR32","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.bbi.2013.10.016","volume":"36","author":"D Hu","year":"2014","unstructured":"Hu D, Wan L, Chen M, Caudle Y, LeSage G, Li Q, Yin D (2014) Essential role of IL-10\/STAT3 in chronic stress-induced immune suppression. Brain Behav Immun 36:118\u2013127","journal-title":"Brain Behav Immun"},{"issue":"2","key":"1751_CR33","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1016\/j.bbrc.2011.06.195","volume":"411","author":"I Hwang","year":"2011","unstructured":"Hwang I, Ha D, Ahn G, Park E, Joo H, Jee Y (2011) Experimental autoimmune encephalomyelitis: association with mutual regulation of RelA (p65)\/NF-kappaB and phospho-IkappaB in the CNS. Biochem Biophys Res Commun 411(2):464\u2013470","journal-title":"Biochem Biophys Res Commun"},{"issue":"1\u20132","key":"1751_CR34","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.jneuroim.2005.10.013","volume":"170","author":"M Jurynczyk","year":"2005","unstructured":"Jurynczyk M, Jurewicz A, Bielecki B, Raine CS, Selmaj K (2005) Inhibition of Notch signaling enhances tissue repair in an animal model of multiple sclerosis. J Neuroimmunol 170(1\u20132):3\u201310","journal-title":"J Neuroimmunol"},{"issue":"4","key":"1751_CR35","doi-asserted-by":"publisher","first-page":"2634","DOI":"10.4049\/jimmunol.180.4.2634","volume":"180","author":"M Jurynczyk","year":"2008","unstructured":"Jurynczyk M, Jurewicz A, Raine CS, Selmaj K (2008) Notch3 inhibition in myelin-reactive T cells down-regulates protein kinase C\u03b8 and attenuates experimental autoimmune encephalomyelitis. J Immunol 180(4):2634\u20132640","journal-title":"J Immunol"},{"key":"1751_CR36","doi-asserted-by":"publisher","first-page":"2936","DOI":"10.1128\/MCB.26.8.2936-2946.2006","volume":"26","author":"B Kaltschmidt","year":"2006","unstructured":"Kaltschmidt B, Ndiaye D, Korte M, Pothion S et al (2006) NF-kappaB regulates spatial memory formation and synaptic plasticity through protein kinase A\/CREB signaling. Mol Cell Biol 26:2936\u20132946","journal-title":"Mol Cell Biol"},{"key":"1751_CR37","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1111\/bpa.12454","volume":"27","author":"M Kipp","year":"2017","unstructured":"Kipp M, Nyamoya S, Hochstrasser T, Amor S (2017) Multiple sclerosis animal models: a clinical and histopathological perspective. Brain Pathol 27:123\u2013137","journal-title":"Brain Pathol"},{"issue":"4","key":"1751_CR38","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1007\/s12272-018-1020-8","volume":"41","author":"S Lee","year":"2018","unstructured":"Lee S, Kim DC, Baek HY, Lee KD, Kim YC, Oh H (2018) Anti-neuroinflammatory effects of tryptanthrin from Polygonum tinctorium Lour. in lipopolysaccharide-stimulated BV2 microglial cells. Arch Pharm Res 41(4):419\u2013430","journal-title":"Arch Pharm Res"},{"issue":"7","key":"1751_CR39","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1038\/s41590-018-0135-x","volume":"19","author":"R Li","year":"2018","unstructured":"Li R, Patterson KR, Bar-Or A (2018) Reassessing B cell contributions in multiple sclerosis. Nat Immunol 19(7):696\u2013707","journal-title":"Nat Immunol"},{"key":"1751_CR40","doi-asserted-by":"publisher","first-page":"5980","DOI":"10.1523\/JNEUROSCI.1636-12.2013","volume":"33","author":"W Lin","year":"2013","unstructured":"Lin W, Lin Y, Li J, Fenstermaker AG, Way SW, Clayton B, Jamison S, Harding HP, Ron D, Popko B (2013) Oligodendrocyte-specific activation of PERK signaling protects mice against experimental autoimmune encephalomyelitis. J Neurosci 33:5980\u20135991","journal-title":"J Neurosci"},{"issue":"1\u20132","key":"1751_CR41","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.jneuroim.2008.09.007","volume":"205","author":"RA Linker","year":"2008","unstructured":"Linker RA, L\u00fchder F, Kallen KJ, Lee DH, Engelhardt B, Rose-John S, Gold R (2008) IL-6 transsignalling modulates the early effector phase of EAE and targets the blood-brain barrier. J Neuroimmunol 205(1\u20132):64\u201372","journal-title":"J Neuroimmunol"},{"key":"1751_CR42","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.jneuroim.2017.05.004","volume":"309","author":"RP Lisak","year":"2017","unstructured":"Lisak RP, Nedelkoska L, Benjamins JA, Schalk D, Bealmear B, Touil H, Li R, Muirhead G, Bar-Or A (2017) B cells from patients with multiple sclerosis induce cell death via apoptosis in neurons in vitro. J Neuroimmunol 309:88\u201399","journal-title":"J Neuroimmunol"},{"key":"1751_CR43","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25:402\u2013408","journal-title":"Methods"},{"issue":"1","key":"1751_CR44","doi-asserted-by":"publisher","first-page":"51","DOI":"10.5114\/fn.2013.34196","volume":"51","author":"S Ljubisavljevic","year":"2013","unstructured":"Ljubisavljevic S, Stojanovic I, Pavlovic D, Milojkovic M, Sokolovic D, Stevanovic I, Petrovic A (2013) Suppression of the lipid peroxidation process in the CNS reduces neurological expression of experimentally induced autoimmune encephalomyelitis. Folia Neuropathol 51(1):51\u201357","journal-title":"Folia Neuropathol"},{"key":"1751_CR84","doi-asserted-by":"publisher","first-page":"2240","DOI":"10.4049\/jimmunol.1001307","volume":"185","author":"T Matsushita","year":"2010","unstructured":"Matsushita T, Horikawa M, Iwata Y, Tedder TF (2010) Regulatory B cells (B10 cells) and regulatory T cellshave independent roles in controlling experimental autoimmune encephalomyelitis initiation andlate-phase immunopathogenesis. J Immunol 185:2240\u20132252","journal-title":"J Immunol"},{"key":"1751_CR46","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1016\/j.molmed.2013.08.001","volume":"19","author":"C Mc Guire","year":"2013","unstructured":"Mc Guire C, Prinz M, Beyaert R, van Loo G (2013) Nuclear factor kappa b (NF-\u03baB) in multiple sclerosis pathology. Trends Mol Med 19:604\u2013613","journal-title":"Trends Mol Med"},{"key":"1751_CR47","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1038\/ni1209x","volume":"6","author":"LM Minter","year":"2005","unstructured":"Minter LM, Turley DM, Das P, Shin HM, Joshi I et al (2005) Inhibitors of gamma-secretase block in vivo and in vitro T helper type 1 polarization by preventing Notch upregulation of Tbx21. Nat Immunol 6:680\u2013688","journal-title":"Nat Immunol"},{"key":"1751_CR48","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.neuropharm.2015.07.013","volume":"99","author":"M Mohajeri","year":"2015","unstructured":"Mohajeri M, Sadeghizadeh M, Najaf F, Javan M (2015) Polymerized nano-curcumin attenuates neurological symptoms in EAE model of multiple sclerosis through down regulation of infammatory and oxidative processes and enhancing neuroprotection and myelin repair. Neuropharmacology 99:156\u2013167","journal-title":"Neuropharmacology"},{"issue":"11","key":"1751_CR49","doi-asserted-by":"publisher","first-page":"5473","DOI":"10.1007\/s12035-021-02497-5","volume":"58","author":"R Nasrnezhad","year":"2021","unstructured":"Nasrnezhad R, Halalkhor S, Sadeghi F, Pourabdolhossein F (2021) Piperine improves experimental autoimmune encephalomyelitis (EAE) in Lewis rats through its neuroprotective, anti-inflammatory, and antioxidant effects. Mol Neurobiol 58(11):5473\u20135493","journal-title":"Mol Neurobiol"},{"issue":"6","key":"1751_CR50","doi-asserted-by":"publisher","first-page":"701","DOI":"10.3390\/antiox13060701","volume":"13","author":"C Nazzi","year":"2024","unstructured":"Nazzi C, Avenanti A, Battaglia S (2024) The involvement of antioxidants in cognitive decline and neurodegeneration: Mens Sana in Corpore Sano. Antioxid (Basel) 13(6):701","journal-title":"Antioxid (Basel)"},{"key":"1751_CR51","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.jaut.2017.10.011","volume":"88","author":"Y Okada","year":"2018","unstructured":"Okada Y, Ochi H, Fujii C, Hashi Y, Hamatani M et al (2018) Signaling via toll-like receptor 4 and CD40 in b cells plays a regulatory role in the pathogenesis of multiple sclerosis through interleukin-10 production. J Autoimmun 88:103\u2013113","journal-title":"J Autoimmun"},{"issue":"3","key":"1751_CR52","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1038\/ki.2010.154","volume":"78","author":"M Pang","year":"2010","unstructured":"Pang M, Ma L, Gong R, Tolbert E et al (2010) A novel STAT3 inhibitor, S3I-201, attenuates renal interstitial fibroblast activation and interstitial fibrosis in obstructive nephropathy. Kidney Int 78(3):257\u2013268","journal-title":"Kidney Int"},{"key":"1751_CR53","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1186\/1742-2094-9-268","volume":"9","author":"B Parajuli","year":"2012","unstructured":"Parajuli B, Sonobe Y, Kawanokuchi J et al (2012) GM-CSF increases LPS-induced production of proinflammatory mediators via upregulation of TLR4 and CD14 in murine microglia. J Neuroinflammation 9:268","journal-title":"J Neuroinflammation"},{"issue":"1\u20132","key":"1751_CR54","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.jneuroim.2010.06.002","volume":"227","author":"JPS Peron","year":"2010","unstructured":"Peron JPS, Yang K, Chen ML et al (2010) Oral tolerance reduces Th17 cells as well as the overall inflammation in the central nervous system of EAE mice. J Neuroimmunol 227(1\u20132):10\u201317","journal-title":"J Neuroimmunol"},{"key":"1751_CR55","doi-asserted-by":"publisher","first-page":"39","DOI":"10.4049\/jimmunol.178.1.39","volume":"178","author":"ED Ponomarev","year":"2007","unstructured":"Ponomarev ED, Shriver LP, Maresz K, Pedras-Vasconcelos J, Verthelyi D, Dittel BN (2007) GM-CSF production by autoreactive T cells is required for the activation of microglial cells and the onset of experimental autoimmune encephalomyelitis. J Immunol 178:39\u201348","journal-title":"J Immunol"},{"key":"1751_CR56","doi-asserted-by":"publisher","first-page":"2079","DOI":"10.4049\/jimmunol.0900242","volume":"183","author":"A Quintana","year":"2009","unstructured":"Quintana A, Muller M, Frausto RF, Ramos R, Getts DR, Sanz E et al (2009) Site-specific production of IL-6 in the central nervous system retargets and enhances the inflammatory response in experimental autoimmune encephalomyelitis. J Immunol 183:2079\u20132088","journal-title":"J Immunol"},{"key":"1751_CR57","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.immuni.2010.01.004","volume":"32","author":"F Radtke","year":"2010","unstructured":"Radtke F, Fasnacht N, Macdonald HR (2010) Notch signaling in the immune system. Immunity 32:14\u201327","journal-title":"Immunity"},{"key":"1751_CR58","doi-asserted-by":"publisher","first-page":"2803","DOI":"10.4049\/jimmunol.1100160","volume":"1 87","author":"ND Reynolds","year":"2011","unstructured":"Reynolds ND, Lukacs NW, Long N, Karpus WJ (2011) Delta-like ligand 4 regulates central nervous system T cell accumulation during experimental autoimmune encephalomyelitis. J Immunol 1 87:2803\u20132813","journal-title":"J Immunol"},{"key":"1751_CR59","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.117671","volume":"253","author":"H Roshanbakhsh","year":"2020","unstructured":"Roshanbakhsh H, Salmani ME, Dehghan S, Nazari A, Javan M, Pourabdolhossein F (2020) Piperine ameliorated memory impairment and myelin damage in lysolecethin induced hippocampal demyelination. Life Sci 253:117671","journal-title":"Life Sci"},{"key":"1751_CR60","unstructured":"Rosner B (2011) Fundamentals of biostatistics, 7th, edn. Brooks\/Cole, Cengage Learning, Boston, Boston"},{"issue":"6 Pt A","key":"1751_CR61","doi-asserted-by":"publisher","first-page":"1218","DOI":"10.1016\/j.bbamcr.2016.03.018","volume":"1863","author":"M Rothaug","year":"2016","unstructured":"Rothaug M, Becker-Pauly C, Rose-John S (2016) The role of interleukin-6 signaling in nervous tissue. Biochim Biophys Acta 1863(6 Pt A):1218\u20131227","journal-title":"Biochim Biophys Acta"},{"issue":"6","key":"1751_CR62","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1007\/s00281-019-00765-0","volume":"41","author":"F Ruiz","year":"2019","unstructured":"Ruiz F, Vigne S, Pot C (2019) Resolution of inflammation during Multiple Sclerosis. Semin Immunopathol 41(6):711\u2013726","journal-title":"Semin Immunopathol"},{"issue":"2","key":"1751_CR63","doi-asserted-by":"publisher","first-page":"330","DOI":"10.3390\/cells9020330","volume":"9","author":"P Sanchis","year":"2020","unstructured":"Sanchis P, Fern\u00e1ndez-Gayol O, Comes G, Escrig A, Giralt M, Palmiter RD, Hidalgo J (2020) Interleukin-6 derived from the central nervous system may influence the pathogenesis of Experimental Autoimmune Encephalomyelitis in a cell-dependent manner. Cells 9(2):330","journal-title":"Cells"},{"issue":"4","key":"1751_CR64","doi-asserted-by":"publisher","first-page":"1606","DOI":"10.4049\/jimmunol.1301116","volume":"191","author":"AR Sandy","year":"2013","unstructured":"Sandy AR, Stoolman J, Malott K, Pongtornpipat P, Segal BM, Maillard I (2013) Notch signaling regulates T cell accumulation and function in the central nervous system during Experimental Autoimmune Encephalomyelitis. J Immunol 191(4):1606\u20131613","journal-title":"J Immunol"},{"key":"1751_CR65","doi-asserted-by":"publisher","first-page":"9041","DOI":"10.1073\/pnas.0802218105","volume":"105","author":"S Serada","year":"2008","unstructured":"Serada S, Fujimoto M, Mihara M, Koike N, Ohsugi Y, Nomura S et al (2008) IL-6 blockade inhibits the induction of myelin antigen-specific Th17 cells and Th1 cells in experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A 105:9041\u20139046","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1751_CR66","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1038\/nature12979","volume":"507","author":"P Shen","year":"2014","unstructured":"Shen P, Roch T, Lampropoulou V, O\u2019Connor RA et al (2014) IL-35-producing B cells are critical regulators of immunity during autoimmune and infectious diseases. Nature 507:366\u2013370","journal-title":"Nature"},{"key":"1751_CR67","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-8-121","volume":"8","author":"W Sheng","year":"2011","unstructured":"Sheng W, Zong Y, Mohammad A, Ajit D, Cui J, Han D et al (2011) Pro-inflammatory cytokines and lipopolysaccharide induce changes in cell morphology, and upregulation of ERK1\/2, iNOS and sPLA(2)-IIA expression in astrocytes and microglia. J Neuroinflammation 8:121","journal-title":"J Neuroinflammation"},{"issue":"18","key":"1751_CR68","doi-asserted-by":"publisher","first-page":"7391","DOI":"10.1073\/pnas.0609757104","volume":"104","author":"K Siddiquee","year":"2007","unstructured":"Siddiquee K, Zhang S, Guida WC et al (2007) Selective chemical probe inhibitor of Stat3, identified through structure-based virtual screening, induces antitumor activity. Proc Natl Acad Sci U S A 104(18):7391\u20137396","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7","key":"1751_CR69","doi-asserted-by":"publisher","first-page":"504","DOI":"10.3109\/08916931003674733","volume":"43","author":"A Slavin","year":"2010","unstructured":"Slavin A, Kelly-Modis L, Labadia M, Ryan K, Brown ML (2010) Pathogenic mechanisms and experimental models of Multiple Sclerosis. Autoimmunity 43(7):504\u2013513","journal-title":"Autoimmunity"},{"key":"1751_CR70","doi-asserted-by":"publisher","first-page":"710","DOI":"10.3389\/fimmu.2019.00710","volume":"10","author":"SA Sonar","year":"2019","unstructured":"Sonar SA, Lal G (2019) The iNOS activity during an immune response controls the CNS pathology in Experimental Autoimmune Encephalomyelitis. Front Immunol 10:710","journal-title":"Front Immunol"},{"key":"1751_CR71","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.clim.2017.04.014","volume":"184","author":"E Staun-Ram","year":"2017","unstructured":"Staun-Ram E, Miller A (2017) Effector and regulatory B cells in Multiple Sclerosis. Clin Immunol 184:11\u201325","journal-title":"Clin Immunol"},{"key":"1751_CR72","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1146\/annurev-immunol-032713-120227","volume":"32","author":"L Steinman","year":"2014","unstructured":"Steinman L (2014) Immunology of relapse and remission in Multiple Sclerosis. Annu Rev Immunol 32:257\u2013281","journal-title":"Annu Rev Immunol"},{"issue":"2","key":"1751_CR73","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1007\/s00401-014-1313-z","volume":"128","author":"O St\u00fcve","year":"2014","unstructured":"St\u00fcve O, Warnke C, Deason K, Stangel M, Kieseier BC, Hartung HP, von B\u00fcdingen HC, Centonze D, Forsthuber TG, Knappertz V (2014) CD19 as a molecular target in CNS autoimmunity. Acta Neuropathol 128(2):177\u201390","journal-title":"Acta Neuropathol"},{"key":"1751_CR74","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1084\/jem.20050923","volume":"202","author":"L Tu","year":"2005","unstructured":"Tu L, Fang TC, Artis D, Shestova O, Pross SE, Maillard I, Pear WS (2005) Notch signaling is an important regulator of type 2 immunity. J Exp Med 202:1037\u20131042","journal-title":"J Exp Med"},{"key":"1751_CR75","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1038\/ni1372","volume":"7","author":"G van Loo","year":"2006","unstructured":"van Loo G, De Lorenzi R, Schmidt H, Huth M, Mildner A, Schmidt-Supprian M, Lassmann H, Prinz MR, Pasparakis M (2006) Inhibition of transcription factor NF-kappaB in the central nervous system ameliorates autoimmune encephalomyelitis in mice. Nat Immunol 7:954\u2013961","journal-title":"Nat Immunol"},{"key":"1751_CR77","doi-asserted-by":"crossref","unstructured":"Wallin MT, Culpepper WJ, Campbell JD et al (2019) The prevalence of MS in the United States. A Popul. Based Estim. Using health claims data 92:e1029\u2013e1040","DOI":"10.1212\/WNL.0000000000007035"},{"key":"1751_CR78","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.neuroscience.2014.04.052","volume":"273","author":"ZF Wang","year":"2014","unstructured":"Wang ZF, Li Q, Liu SB, Mi WL, Hu S, Zhao J et al (2014) Aspirin-triggered Lipoxin A4 attenuates mechanical allodynia in association with inhibiting spinal JAK2\/STAT3 signaling in neuropathic pain in rats. Neuroscience 273:65\u201378","journal-title":"Neuroscience"},{"key":"1751_CR79","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.jneuroim.2007.09.007","volume":"191","author":"DO Willenborg","year":"2007","unstructured":"Willenborg DO, Staykova M, Fordham S, O\u2019Brien N, Linares D (2007) The contribution of nitric oxide and interferon gamma to the regulation of the neuro-inflammation in experimental autoimmune encephalomyelitis. J Neuroimmunol 191:16\u201325","journal-title":"J Neuroimmunol"},{"issue":"6","key":"1751_CR80","doi-asserted-by":"publisher","first-page":"536","DOI":"10.2174\/187152708787122941","volume":"7","author":"J Yan","year":"2008","unstructured":"Yan J, Greer JM (2008) NF-kappa B, a potential therapeutic target for the treatment of multiple sclerosis. CNS Neurol Disord Drug Targets 7(6):536\u2013557","journal-title":"CNS Neurol Disord Drug Targets"},{"key":"1751_CR81","doi-asserted-by":"publisher","first-page":"2115","DOI":"10.4049\/jimmunol.1203546","volume":"191","author":"QQ Yin","year":"2013","unstructured":"Yin QQ, Liu CX, Wu YL, Wu SF, Wang Y et al (2013) Preventive and therapeutic effects of adenanthin on experimental autoimmune encephalomyelitis by inhibiting NF-\u03baB signaling. J Immunol 191:2115\u20132125","journal-title":"J Immunol"},{"key":"1751_CR82","doi-asserted-by":"publisher","first-page":"322","DOI":"10.3389\/fncel.2015.00322","volume":"9","author":"JE Yuste","year":"2015","unstructured":"Yuste JE, Tarragon E, Campuzano CM, Ros-Bernal F (2015) Implications of glial nitric oxide in neurodegenerative diseases. Front Cell Neurosci 9:322","journal-title":"Front Cell Neurosci"},{"key":"1751_CR83","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00391","volume":"11","author":"Y Zhou","year":"2020","unstructured":"Zhou Y, Cui C, Ma X, Luo W, Zheng SG, Qiu W (2020) Nuclear factor \u03baB (NF-\u03baB)-mediated inflammation in multiple sclerosis. Front Immunol 11:391","journal-title":"Front Immunol"}],"container-title":["Cellular and Molecular Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10571-026-01751-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10571-026-01751-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10571-026-01751-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T01:02:37Z","timestamp":1784250157000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10571-026-01751-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,24]]},"references-count":80,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1751"],"URL":"https:\/\/doi.org\/10.1007\/s10571-026-01751-5","relation":{},"ISSN":["1573-6830"],"issn-type":[{"value":"1573-6830","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,24]]},"assertion":[{"value":"30 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing Interests","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The animal study protocol was approved by the Ethical Committee of the College of Pharmacy, King Saud University (Ethical Reference No: KSU-SE-22-32).","order":2,"name":"Ethics","label":"Ethical Approval","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"116"}}