{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:32:55Z","timestamp":1790793175854,"version":"4.1.0"},"reference-count":70,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2016,4,30]],"date-time":"2016-04-30T00:00:00Z","timestamp":1461974400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Neurobiol"],"published-print":{"date-parts":[[2017,7]]},"DOI":"10.1007\/s12035-016-9893-3","type":"journal-article","created":{"date-parts":[[2016,4,30]],"date-time":"2016-04-30T01:07:25Z","timestamp":1461978445000},"page":"3271-3285","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Inosine, an Endogenous Purine Nucleoside, Suppresses Immune Responses and Protects Mice from Experimental Autoimmune Encephalomyelitis: a Role for A2A Adenosine Receptor"],"prefix":"10.1007","volume":"54","author":[{"given":"Stella C\u00e9lio","family":"Junqueira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"dos Santos Coelho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente","family":"Lieberknecht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauricio Pe\u00f1a","family":"Cunha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o B.","family":"Calixto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana L\u00facia S.","family":"Rodrigues","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adair Roberto Soares","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael Cypriano","family":"Dutra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,4,30]]},"reference":[{"issue":"4","key":"9893_CR1","doi-asserted-by":"publisher","first-page":"1180","DOI":"10.1172\/JCI58649","volume":"122","author":"A Nylander","year":"2012","unstructured":"Nylander A, Hafler DA (2012) Multiple sclerosis. J Clin Invest 122(4):1180\u20131188. doi: 10.1172\/JCI58649","journal-title":"J Clin Invest"},{"issue":"7","key":"9893_CR2","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1016\/S1474-4422(14)70041-9","volume":"13","author":"S Sawcer","year":"2014","unstructured":"Sawcer S, Franklin RJ, Ban M (2014) Multiple sclerosis genetics. Lancet Neurol 13(7):700\u2013709. doi: 10.1016\/S1474-4422(14)70041-9","journal-title":"Lancet Neurol"},{"issue":"5","key":"9893_CR3","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1177\/1352458511424422","volume":"18","author":"J Blahova Dusankova","year":"2012","unstructured":"Blahova Dusankova J, Kalincik T, Dolezal T, Kobelt G, Havrdova E (2012) Cost of multiple sclerosis in the Czech Republic: the COMS study. Mult Scler 18(5):662\u2013668. doi: 10.1177\/1352458511424422","journal-title":"Mult Scler"},{"key":"9893_CR4","unstructured":"Federation MSI (2013) Atlas of MS 2013. http:\/\/www.atlasofms.org\/ . Accessed 23 de maio 2014"},{"issue":"6","key":"9893_CR5","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1016\/S1474-4422(10)70086-7","volume":"9","author":"A Ascherio","year":"2010","unstructured":"Ascherio A, Munger KL, Simon KC (2010) Vitamin D and multiple sclerosis. Lancet Neurol 9(6):599\u2013612. doi: 10.1016\/S1474-4422(10)70086-7","journal-title":"Lancet Neurol"},{"issue":"2","key":"9893_CR6","doi-asserted-by":"publisher","first-page":"e4565","DOI":"10.1371\/journal.pone.0004565","volume":"4","author":"DS Goodin","year":"2009","unstructured":"Goodin DS (2009) The causal cascade to multiple sclerosis: a model for MS pathogenesis. PLoS One 4(2):e4565. doi: 10.1371\/journal.pone.0004565","journal-title":"PLoS One"},{"issue":"9","key":"9893_CR7","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1038\/Ni1507","volume":"8","author":"HF McFarland","year":"2007","unstructured":"McFarland HF, Martin R (2007) Multiple sclerosis: a complicated picture of autoimmunity. Nat Immunol 8(9):913\u2013919. doi: 10.1038\/Ni1507","journal-title":"Nat Immunol"},{"issue":"9648","key":"9893_CR8","doi-asserted-by":"publisher","first-page":"1502","DOI":"10.1016\/S0140-6736(08)61620-7","volume":"372","author":"A Compston","year":"2008","unstructured":"Compston A, Coles A (2008) Multiple sclerosis. Lancet 372(9648):1502\u20131517. doi: 10.1016\/S0140-6736(08)61620-7","journal-title":"Lancet"},{"issue":"1","key":"9893_CR9","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.clim.2011.03.004","volume":"142","author":"M Comabella","year":"2012","unstructured":"Comabella M, Khoury SJ (2012) Immunopathogenesis of multiple sclerosis. Clin Immunol 142(1):2\u20138. doi: 10.1016\/j.clim.2011.03.004","journal-title":"Clin Immunol"},{"issue":"1","key":"9893_CR10","doi-asserted-by":"crossref","first-page":"566","DOI":"10.4049\/jimmunol.177.1.566","volume":"177","author":"Y Komiyama","year":"2006","unstructured":"Komiyama Y, Nakae S, Matsuki T, Nambu A, Ishigame H, Kakuta S, Sudo K, Iwakura Y (2006) IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis. J Immunol 177(1):566\u2013573","journal-title":"J Immunol"},{"issue":"1","key":"9893_CR11","doi-asserted-by":"publisher","first-page":"146","DOI":"10.2353\/ajpath.2008.070690","volume":"172","author":"JS Tzartos","year":"2008","unstructured":"Tzartos JS, Friese MA, Craner MJ, Palace J, Newcombe J, Esiri MM, Fugger L (2008) Interleukin-17 production in central nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis. Am J Pathol 172(1):146\u2013155. doi: 10.2353\/ajpath.2008.070690","journal-title":"Am J Pathol"},{"issue":"2","key":"9893_CR12","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S1359-6101(03)00002-9","volume":"14","author":"TA Moseley","year":"2003","unstructured":"Moseley TA, Haudenschild DR, Rose L, Reddi AH (2003) Interleukin-17 family and IL-17 receptors. Cytokine Growth Factor Rev 14(2):155\u2013174","journal-title":"Cytokine Growth Factor Rev"},{"issue":"3","key":"9893_CR13","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/nm1715","volume":"14","author":"IM Stromnes","year":"2008","unstructured":"Stromnes IM, Cerretti LM, Liggitt D, Harris RA, Goverman JM (2008) Differential regulation of central nervous system autoimmunity by T(H)1 and T(H)17 cells. Nat Med 14(3):337\u2013342. doi: 10.1038\/nm1715","journal-title":"Nat Med"},{"issue":"1","key":"9893_CR14","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.pain.2007.08.024","volume":"137","author":"AB O\u2019Connor","year":"2008","unstructured":"O\u2019Connor AB, Schwid SR, Herrmann DN, Markman JD, Dworkin RH (2008) Pain associated with multiple sclerosis: systematic review and proposed classification. Pain 137(1):96\u2013111. doi: 10.1016\/j.pain.2007.08.024","journal-title":"Pain"},{"issue":"4","key":"9893_CR15","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1007\/s10072-013-1544-0","volume":"35","author":"B Goretti","year":"2014","unstructured":"Goretti B, Viterbo RG, Portaccio E, Niccolai C, Hakiki B, Piscolla E, Iaffaldano P, Trojano M et al (2014) Anxiety state affects information processing speed in patients with multiple sclerosis. Neurol Sci 35(4):559\u2013563. doi: 10.1007\/s10072-013-1544-0","journal-title":"Neurol Sci"},{"issue":"7","key":"9893_CR16","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/j.disamonth.2013.03.014","volume":"59","author":"SM Rubin","year":"2013","unstructured":"Rubin SM (2013) Management of cognition and fatigue. Dis Mon 59(7):269\u2013272. doi: 10.1016\/j.disamonth.2013.03.014","journal-title":"Dis Mon"},{"issue":"Suppl 1","key":"9893_CR17","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1159\/000367620","volume":"72","author":"P Gallien","year":"2014","unstructured":"Gallien P, Gich J, Sanchez-Dalmau BF, Feneberg W (2014) Multidisciplinary management of multiple sclerosis symptoms. Eur Neurol 72(Suppl 1):20\u201325. doi: 10.1159\/000367620","journal-title":"Eur Neurol"},{"issue":"4","key":"9893_CR18","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1016\/j.bcp.2011.11.026","volume":"83","author":"RC Dutra","year":"2012","unstructured":"Dutra RC, de Souza PR, Bento AF, Marcon R, Bicca MA, Pianowski LF, Calixto JB (2012) Euphol prevents experimental autoimmune encephalomyelitis in mice: evidence for the underlying mechanisms. Biochem Pharmacol 83(4):531\u2013542. doi: 10.1016\/j.bcp.2011.11.026","journal-title":"Biochem Pharmacol"},{"key":"9893_CR19","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.nbd.2013.02.007","volume":"54","author":"RC Dutra","year":"2013","unstructured":"Dutra RC, Bento AF, Leite DF, Manjavachi MN, Marcon R, Bicca MA, Pesquero JB, Calixto JB (2013) The role of kinin B1 and B2 receptors in the persistent pain induced by experimental autoimmune encephalomyelitis (EAE) in mice: evidence for the involvement of astrocytes. Neurobiol Dis 54:82\u201393. doi: 10.1016\/j.nbd.2013.02.007","journal-title":"Neurobiol Dis"},{"issue":"3","key":"9893_CR20","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1016\/j.jpain.2010.08.003","volume":"12","author":"CF Kim","year":"2011","unstructured":"Kim CF, Moalem-Taylor G (2011) Interleukin-17 contributes to neuroinflammation and neuropathic pain following peripheral nerve injury in mice. J Pain 12(3):370\u2013383. doi: 10.1016\/j.jpain.2010.08.003","journal-title":"J Pain"},{"key":"9893_CR21","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.brainres.2014.01.044","volume":"1555","author":"S Dachir","year":"2014","unstructured":"Dachir S, Shabashov D, Trembovler V, Alexandrovich AG, Benowitz LI, Shohami E (2014) Inosine improves functional recovery after experimental traumatic brain injury. Brain Res 1555:78\u201388. doi: 10.1016\/j.brainres.2014.01.044","journal-title":"Brain Res"},{"issue":"12","key":"9893_CR22","doi-asserted-by":"publisher","first-page":"e81948","DOI":"10.1371\/journal.pone.0081948","volume":"8","author":"D Kim","year":"2013","unstructured":"Kim D, Zai L, Liang P, Schaffling C, Ahlborn D, Benowitz LI (2013) Inosine enhances axon sprouting and motor recovery after spinal cord injury. PLoS One 8(12):e81948. doi: 10.1371\/journal.pone.0081948","journal-title":"PLoS One"},{"issue":"Pt 4","key":"9893_CR23","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1093\/brain\/awl393","volume":"130","author":"JM Smith","year":"2007","unstructured":"Smith JM, Lunga P, Story D, Harris N, Le Belle J, James MF, Pickard JD, Fawcett JW (2007) Inosine promotes recovery of skilled motor function in a model of focal brain injury. Brain: J Neurol 130(Pt 4):915\u2013925. doi: 10.1093\/brain\/awl393","journal-title":"Brain: J Neurol"},{"issue":"25","key":"9893_CR24","doi-asserted-by":"publisher","first-page":"8187","DOI":"10.1523\/JNEUROSCI.0414-09.2009","volume":"29","author":"L Zai","year":"2009","unstructured":"Zai L, Ferrari C, Subbaiah S, Havton LA, Coppola G, Strittmatter S, Irwin N, Geschwind D et al (2009) Inosine alters gene expression and axonal projections in neurons contralateral to a cortical infarct and improves skilled use of the impaired limb. J Neurosci 29(25):8187\u20138197. doi: 10.1523\/JNEUROSCI.0414-09.2009","journal-title":"J Neurosci"},{"issue":"3","key":"9893_CR25","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/j.tips.2004.01.006","volume":"25","author":"G Hasko","year":"2004","unstructured":"Hasko G, Sitkovsky MV, Szabo C (2004) Immunomodulatory and neuroprotective effects of inosine. Trends Pharmacol Sci 25(3):152\u2013157. doi: 10.1016\/j.tips.2004.01.006","journal-title":"Trends Pharmacol Sci"},{"issue":"3","key":"9893_CR26","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1007\/s11302-013-9351-x","volume":"9","author":"F Rocha Lapa da","year":"2013","unstructured":"da Rocha Lapa F, de Oliveira AP, Accetturi BG, de Oliveira MI, Domingos HV, de Almeida CD, de Lima WT, Santos AR (2013) Anti-inflammatory effects of inosine in allergic lung inflammation in mice: evidence for the participation of adenosine A2A and A 3 receptors. Purinergic signal 9(3):325\u2013336. doi: 10.1007\/s11302-013-9351-x","journal-title":"Purinergic signal"},{"issue":"4","key":"9893_CR27","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1007\/s11302-012-9299-2","volume":"8","author":"LF Rocha da","year":"2012","unstructured":"da Rocha LF, da Silva MD, de Almeida CD, Santos AR (2012) Anti-inflammatory effects of purine nucleosides, adenosine and inosine, in a mouse model of pleurisy: evidence for the role of adenosine A2 receptors. Purinergic Signal 8(4):693\u2013704. doi: 10.1007\/s11302-012-9299-2","journal-title":"Purinergic Signal"},{"issue":"2","key":"9893_CR28","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1124\/jpet.110.166058","volume":"334","author":"FP Nascimento","year":"2010","unstructured":"Nascimento FP, Figueredo SM, Marcon R, Martins DF, Macedo SJ Jr, Lima DA, Almeida RC, Ostroski RM et al (2010) Inosine reduces pain-related behavior in mice: involvement of adenosine A1 and A2A receptor subtypes and protein kinase C pathways. J Pharmacol Exp Ther 334(2):590\u2013598. doi: 10.1124\/jpet.110.166058","journal-title":"J Pharmacol Exp Ther"},{"key":"9893_CR29","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-014-8815-5","author":"FP Nascimento","year":"2014","unstructured":"Nascimento FP, Macedo-Junior SJ, Pamplona FA, Luiz-Cerutti M, Cordova MM, Constantino L, Tasca CI, Dutra RC et al (2014) Adenosine A1 receptor-dependent antinociception induced by inosine in mice: pharmacological. Genetic Biochem Aspects Mol Neurobiol. doi: 10.1007\/s12035-014-8815-5","journal-title":"Genetic Biochem Aspects Mol Neurobiol"},{"issue":"3","key":"9893_CR30","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1007\/s11302-013-9361-8","volume":"9","author":"MP Kaster","year":"2013","unstructured":"Kaster MP, Budni J, Gazal M, Cunha MP, Santos AR, Rodrigues AL (2013) The antidepressant-like effect of inosine in the FST is associated with both adenosine A1 and A 2A receptors. Purinergic Signal 9(3):481\u2013486. doi: 10.1007\/s11302-013-9361-8","journal-title":"Purinergic Signal"},{"issue":"4","key":"9893_CR31","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/S0031-6997(24)01511-4","volume":"53","author":"BB Fredholm","year":"2001","unstructured":"Fredholm BB, IJzerman AP, Jacobson KA, Klotz KN, Linden J (2001) International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol Rev 53(4):527\u2013552","journal-title":"Pharmacol Rev"},{"issue":"3","key":"9893_CR32","doi-asserted-by":"publisher","first-page":"L569","DOI":"10.1152\/ajplung.00278.2004","volume":"288","author":"S Buckley","year":"2005","unstructured":"Buckley S, Barsky L, Weinberg K, Warburton D (2005) In vivo inosine protects alveolar epithelial type 2 cells against hyperoxia-induced DNA damage through MAP kinase signaling. Am J Physiol Lung Cell Mol Physiol 288(3):L569\u2013L575. doi: 10.1152\/ajplung.00278.2004","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"issue":"4","key":"9893_CR33","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1016\/j.mcn.2008.05.004","volume":"38","author":"B Tomaselli","year":"2008","unstructured":"Tomaselli B, Nedden SZ, Podhraski V, Baier-Bitterlich G (2008) p42\/44 MAPK is an essential effector for purine nucleoside-mediated neuroprotection of hypoxic PC12 cells and primary cerebellar granule neurons. Mol Cell Neurosci 38(4):559\u2013568. doi: 10.1016\/j.mcn.2008.05.004","journal-title":"Mol Cell Neurosci"},{"issue":"7001","key":"9893_CR34","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1038\/nature02764","volume":"430","author":"Y Zhang","year":"2004","unstructured":"Zhang Y, Blattman JN, Kennedy NJ, Duong J, Nguyen T, Wang Y, Davis RJ, Greenberg PD et al (2004) Regulation of innate and adaptive immune responses by MAP kinase phosphatase 5. Nature 430(7001):793\u2013797. doi: 10.1038\/nature02764","journal-title":"Nature"},{"issue":"10","key":"9893_CR35","doi-asserted-by":"crossref","first-page":"5788","DOI":"10.4049\/jimmunol.176.10.5788","volume":"176","author":"A Agrawal","year":"2006","unstructured":"Agrawal A, Dillon S, Denning TL, Pulendran B (2006) ERK1\u2212\/\u2212 mice exhibit Th1 cell polarization and increased susceptibility to experimental autoimmune encephalomyelitis. J Immunol 176(10):5788\u20135796","journal-title":"J Immunol"},{"issue":"6","key":"9893_CR36","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1089\/acm.2008.0513","volume":"15","author":"CE Markowitz","year":"2009","unstructured":"Markowitz CE, Spitsin S, Zimmerman V, Jacobs D, Udupa JK, Hooper DC, Koprowski H (2009) The treatment of multiple sclerosis with inosine. J Altern Complement Med 15(6):619\u2013625. doi: 10.1089\/acm.2008.0513","journal-title":"J Altern Complement Med"},{"issue":"10","key":"9893_CR37","doi-asserted-by":"crossref","first-page":"879","DOI":"10.2298\/VSP0610879T","volume":"63","author":"G Toncev","year":"2006","unstructured":"Toncev G (2006) Therapeutic value of serum uric acid levels increasing in the treatment of multiple sclerosis. Vojnosanitetski Pregled Military-Med Pharmaceut Rev 63(10):879\u2013882","journal-title":"Vojnosanitetski Pregled Military-Med Pharmaceut Rev"},{"issue":"11","key":"9893_CR38","doi-asserted-by":"publisher","first-page":"5713","DOI":"10.4049\/jimmunol.1200545","volume":"188","author":"JH Mills","year":"2012","unstructured":"Mills JH, Kim DG, Krenz A, Chen JF, Bynoe MS (2012) A2A adenosine receptor signaling in lymphocytes and the central nervous system regulates inflammation during experimental autoimmune encephalomyelitis. J Immunol 188(11):5713\u20135722. doi: 10.4049\/jimmunol.1200545","journal-title":"J Immunol"},{"issue":"4","key":"9893_CR39","doi-asserted-by":"publisher","first-page":"1810","DOI":"10.1038\/nprot.2006.285","volume":"1","author":"IM Stromnes","year":"2006","unstructured":"Stromnes IM, Goverman JM (2006) Active induction of experimental allergic encephalomyelitis. Nat Protoc 1(4):1810\u20131819. doi: 10.1038\/nprot.2006.285","journal-title":"Nat Protoc"},{"key":"9893_CR40","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1186\/1742-2094-9-233","volume":"9","author":"J Lu","year":"2012","unstructured":"Lu J, Kurejova M, Wirotanseng LN, Linker RA, Kuner R, Tappe-Theodor A (2012) Pain in experimental autoimmune encephalitis: a comparative study between different mouse models. J Neuroinflammation 9:233. doi: 10.1186\/1742-2094-9-233","journal-title":"J Neuroinflammation"},{"issue":"3","key":"9893_CR41","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1016\/j.neulet.2006.01.058","volume":"399","author":"JS Walczak","year":"2006","unstructured":"Walczak JS, Beaulieu P (2006) Comparison of three models of neuropathic pain in mice using a new method to assess cold allodynia: the double plate technique. Neurosci Lett 399(3):240\u2013244. doi: 10.1016\/j.neulet.2006.01.058","journal-title":"Neurosci Lett"},{"issue":"2","key":"9893_CR42","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.4049\/jimmunol.174.2.1073","volume":"174","author":"CM Lappas","year":"2005","unstructured":"Lappas CM, Rieger JM, Linden J (2005) A2A adenosine receptor induction inhibits IFN-gamma production in murine CD4+ T cells. J Immunol 174(2):1073\u20131080","journal-title":"J Immunol"},{"issue":"5","key":"9893_CR43","doi-asserted-by":"publisher","first-page":"528","DOI":"10.7150\/ijms.8220","volume":"11","author":"KY Su","year":"2014","unstructured":"Su KY, Yu CY, Chen YW, Huang YT, Chen CT, Wu HF, Chen YL (2014) Rutin, a flavonoid and principal component of saussurea involucrata, attenuates physical fatigue in a forced swimming mouse model. Int J Med Sci 11(5):528\u2013537. doi: 10.7150\/ijms.8220","journal-title":"Int J Med Sci"},{"issue":"1","key":"9893_CR44","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1177\/1352458508096687","volume":"15","author":"A Gajofatto","year":"2009","unstructured":"Gajofatto A, Bacchetti P, Grimes B, High A, Waubant E (2009) Switching first-line disease-modifying therapy after failure: impact on the course of relapsing-remitting multiple sclerosis. Mult Scler 15(1):50\u201358. doi: 10.1177\/1352458508096687","journal-title":"Mult Scler"},{"key":"9893_CR45","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.bbi.2014.02.003","volume":"40","author":"S Ouyang","year":"2014","unstructured":"Ouyang S, Hsuchou H, Kastin AJ, Mishra PK, Wang Y, Pan W (2014) Leukocyte infiltration into spinal cord of EAE mice is attenuated by removal of endothelial leptin signaling. Brain Behav Immun 40:61\u201373. doi: 10.1016\/j.bbi.2014.02.003","journal-title":"Brain Behav Immun"},{"issue":"11","key":"9893_CR46","doi-asserted-by":"publisher","first-page":"e27875","DOI":"10.1371\/journal.pone.0027875","volume":"6","author":"RC Dutra","year":"2011","unstructured":"Dutra RC, Leite DF, Bento AF, Manjavachi MN, Patricio ES, Figueiredo CP, Pesquero JB, Calixto JB (2011) The role of kinin receptors in preventing neuroinflammation and its clinical severity during experimental autoimmune encephalomyelitis in mice. PLoS One 6(11):e27875. doi: 10.1371\/journal.pone.0027875","journal-title":"PLoS One"},{"issue":"3","key":"9893_CR47","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1002\/glia.22616","volume":"62","author":"R Brambilla","year":"2014","unstructured":"Brambilla R, Morton PD, Ashbaugh JJ, Karmally S, Lambertsen KL, Bethea JR (2014) Astrocytes play a key role in EAE pathophysiology by orchestrating in the CNS the inflammatory response of resident and peripheral immune cells and by suppressing remyelination. Glia 62(3):452\u2013467. doi: 10.1002\/glia.22616","journal-title":"Glia"},{"issue":"2","key":"9893_CR48","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1111\/j.1365-2567.2008.02837.x","volume":"125","author":"CJ Hedegaard","year":"2008","unstructured":"Hedegaard CJ, Krakauer M, Bendtzen K, Lund H, Sellebjerg F, Nielsen CH (2008) T helper cell type 1 (Th1), Th2 and Th17 responses to myelin basic protein and disease activity in multiple sclerosis. Immunology 125(2):161\u2013169. doi: 10.1111\/j.1365-2567.2008.02837.x","journal-title":"Immunology"},{"issue":"6","key":"9893_CR49","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.1523\/JNEUROSCI.4271-03.2004","volume":"24","author":"S Tsutsui","year":"2004","unstructured":"Tsutsui S, Schnermann J, Noorbakhsh F, Henry S, Yong VW, Winston BW, Warren K, Power C (2004) A1 adenosine receptor upregulation and activation attenuates neuroinflammation and demyelination in a model of multiple sclerosis. J Neurosci 24(6):1521\u20131529. doi: 10.1523\/JNEUROSCI.4271-03.2004","journal-title":"J Neurosci"},{"issue":"8","key":"9893_CR50","doi-asserted-by":"publisher","first-page":"2206","DOI":"10.1002\/eji.201343314","volume":"43","author":"F Vincenzi","year":"2013","unstructured":"Vincenzi F, Corciulo C, Targa M, Merighi S, Gessi S, Casetta I, Gentile M, Granieri E et al (2013) Multiple sclerosis lymphocytes upregulate A2A adenosine receptors that are antiinflammatory when stimulated. Eur J Immunol 43(8):2206\u20132216. doi: 10.1002\/eji.201343314","journal-title":"Eur J Immunol"},{"issue":"1\u20132","key":"9893_CR51","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/S0165-5728(03)00174-7","volume":"140","author":"T Shin","year":"2003","unstructured":"Shin T, Ahn M, Jung K, Heo S, Kim D, Jee Y, Lim YK, Yeo EJ (2003) Activation of mitogen-activated protein kinases in experimental autoimmune encephalomyelitis. J Neuroimmunol 140(1\u20132):118\u2013125","journal-title":"J Neuroimmunol"},{"key":"9893_CR52","unstructured":"Hauser SL GD (2008) Multiple sclerosis and other demyelinating diseases. In: Harrison\u2019s Principles of Internal Medicine, vol II. McGraw-Hill Medical, New York, pp 2611\u20132621"},{"key":"9893_CR53","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/j.bbi.2013.07.003","volume":"33","author":"S Acharjee","year":"2013","unstructured":"Acharjee S, Nayani N, Tsutsui M, Hill MN, Ousman SS, Pittman QJ (2013) Altered cognitive-emotional behavior in early experimental autoimmune encephalitis\u2014cytokine and hormonal correlates. Brain Behav Immun 33:164\u2013172. doi: 10.1016\/j.bbi.2013.07.003","journal-title":"Brain Behav Immun"},{"issue":"1","key":"9893_CR54","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.bbr.2011.01.018","volume":"220","author":"I Peruga","year":"2011","unstructured":"Peruga I, Hartwig S, Thone J, Hovemann B, Gold R, Juckel G, Linker RA (2011) Inflammation modulates anxiety in an animal model of multiple sclerosis. Behav Brain Res 220(1):20\u201329. doi: 10.1016\/j.bbr.2011.01.018","journal-title":"Behav Brain Res"},{"issue":"1","key":"9893_CR55","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1002\/ana.23758","volume":"73","author":"RA Bermel","year":"2013","unstructured":"Bermel RA, You X, Foulds P, Hyde R, Simon JH, Fisher E, Rudick RA (2013) Predictors of long-term outcome in multiple sclerosis patients treated with interferon beta. Ann Neurol 73(1):95\u2013103. doi: 10.1002\/ana.23758","journal-title":"Ann Neurol"},{"issue":"9","key":"9893_CR56","doi-asserted-by":"publisher","first-page":"1394","DOI":"10.1038\/jcbfm.2013.85","volume":"33","author":"E Rissanen","year":"2013","unstructured":"Rissanen E, Virta JR, Paavilainen T, Tuisku J, Helin S, Luoto P, Parkkola R, Rinne JO et al (2013) Adenosine A2A receptors in secondary progressive multiple sclerosis: a [(11)C]TMSX brain PET study. J Cereb Blood Flow Metab 33(9):1394\u20131401. doi: 10.1038\/jcbfm.2013.85","journal-title":"J Cereb Blood Flow Metab"},{"issue":"3","key":"9893_CR57","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1096\/fj.07-9002com","volume":"22","author":"S Tsutsui","year":"2008","unstructured":"Tsutsui S, Vergote D, Shariat N, Warren K, Ferguson SS, Power C (2008) Glucocorticoids regulate innate immunity in a model of multiple sclerosis: reciprocal interactions between the A1 adenosine receptor and beta-arrestin-1 in monocytoid cells. FASEB J 22(3):786\u2013796. doi: 10.1096\/fj.07-9002com","journal-title":"FASEB J"},{"issue":"11","key":"9893_CR58","doi-asserted-by":"crossref","first-page":"6511","DOI":"10.4049\/jimmunol.165.11.6511","volume":"165","author":"RB Kean","year":"2000","unstructured":"Kean RB, Spitsin SV, Mikheeva T, Scott GS, Hooper DC (2000) The peroxynitrite scavenger uric acid prevents inflammatory cell invasion into the central nervous system in experimental allergic encephalomyelitis through maintenance of blood-central nervous system barrier integrity. J Immunol 165(11):6511\u20136518","journal-title":"J Immunol"},{"issue":"10","key":"9893_CR59","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1038\/nm1651","volume":"13","author":"H Kebir","year":"2007","unstructured":"Kebir H, Kreymborg K, Ifergan I, Dodelet-Devillers A, Cayrol R, Bernard M, Giuliani F, Arbour N et al (2007) Human TH17 lymphocytes promote blood\u2013brain barrier disruption and central nervous system inflammation. Nat Med 13(10):1173\u20131175. doi: 10.1038\/nm1651","journal-title":"Nat Med"},{"issue":"4","key":"9893_CR60","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.4049\/jimmunol.170.4.2153","volume":"170","author":"GX Zhang","year":"2003","unstructured":"Zhang GX, Gran B, Yu S, Li J, Siglienti I, Chen X, Kamoun M, Rostami A (2003) Induction of experimental autoimmune encephalomyelitis in IL-12 receptor-beta 2-deficient mice: IL-12 responsiveness is not required in the pathogenesis of inflammatory demyelination in the central nervous system. J Immunol 170(4):2153\u20132160","journal-title":"J Immunol"},{"issue":"1","key":"9893_CR61","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1038\/71555","volume":"6","author":"D Pitt","year":"2000","unstructured":"Pitt D, Werner P, Raine CS (2000) Glutamate excitotoxicity in a model of multiple sclerosis. Nat Med 6(1):67\u201370. doi: 10.1038\/71555","journal-title":"Nat Med"},{"issue":"4","key":"9893_CR62","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1084\/jem.20072404","volume":"205","author":"T Carlson","year":"2008","unstructured":"Carlson T, Kroenke M, Rao P, Lane TE, Segal B (2008) The Th17-ELR+ CXC chemokine pathway is essential for the development of central nervous system autoimmune disease. J Exp Med 205(4):811\u2013823. doi: 10.1084\/jem.20072404","journal-title":"J Exp Med"},{"issue":"3","key":"9893_CR63","doi-asserted-by":"publisher","first-page":"1715","DOI":"10.4049\/jimmunol.0803851","volume":"183","author":"CF Brereton","year":"2009","unstructured":"Brereton CF, Sutton CE, Lalor SJ, Lavelle EC, Mills KH (2009) Inhibition of ERK MAPK suppresses IL-23- and IL-1-driven IL-17 production and attenuates autoimmune disease. J Immunol 183(3):1715\u20131723. doi: 10.4049\/jimmunol.0803851","journal-title":"J Immunol"},{"issue":"1","key":"9893_CR64","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.ejpain.2009.03.003","volume":"14","author":"A Osterberg","year":"2010","unstructured":"Osterberg A, Boivie J (2010) Central pain in multiple sclerosis\u2014sensory abnormalities. Eur J Pain 14(1):104\u2013110. doi: 10.1016\/j.ejpain.2009.03.003","journal-title":"Eur J Pain"},{"issue":"7","key":"9893_CR65","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1016\/j.pain.2014.04.004","volume":"155","author":"YJ Day","year":"2014","unstructured":"Day YJ, Liou JT, Lee CM, Lin YC, Mao CC, Chou AH, Liao CC, Lee HC (2014) Lack of interleukin-17 leads to a modulated micro-environment and amelioration of mechanical hypersensitivity after peripheral nerve injury in mice. Pain 155(7):1293\u20131302. doi: 10.1016\/j.pain.2014.04.004","journal-title":"Pain"},{"key":"9893_CR66","doi-asserted-by":"publisher","first-page":"4199","DOI":"10.1038\/srep04199","volume":"4","author":"J Muto","year":"2014","unstructured":"Muto J, Lee H, Lee H, Uwaya A, Park J, Nakajima S, Nagata K, Ohno M et al (2014) Oral administration of inosine produces antidepressant-like effects in mice. Sci Rep 4:4199. doi: 10.1038\/srep04199","journal-title":"Sci Rep"},{"key":"9893_CR67","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.bbr.2014.05.038","volume":"271","author":"RN Hughes","year":"2014","unstructured":"Hughes RN, Hancock NJ, Henwood GA, Rapley SA (2014) Evidence for anxiolytic effects of acute caffeine on anxiety-related behavior in male and female rats tested with and without bright light. Behav Brain Res 271:7\u201315. doi: 10.1016\/j.bbr.2014.05.038","journal-title":"Behav Brain Res"},{"issue":"5","key":"9893_CR68","first-page":"439","volume":"45","author":"SK Kulkarni","year":"2007","unstructured":"Kulkarni SK, Singh K, Bishnoi M (2007) Involvement of adenosinergic receptors in anxiety related behaviours. Indian J Exp Biol 45(5):439\u2013443","journal-title":"Indian J Exp Biol"},{"issue":"2","key":"9893_CR69","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1177\/135245850000600213","volume":"6","author":"DC Kroencke","year":"2000","unstructured":"Kroencke DC, Lynch SG, Denney DR (2000) Fatigue in multiple sclerosis: relationship to depression, disability, and disease pattern. Mult Scler 6(2):131\u2013136","journal-title":"Mult Scler"},{"issue":"2","key":"9893_CR70","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1191\/1352458504ms991oa","volume":"10","author":"P Flachenecker","year":"2004","unstructured":"Flachenecker P, Bihler I, Weber F, Gottschalk M, Toyka KV, Rieckmann P (2004) Cytokine mRNA expression in patients with multiple sclerosis and fatigue. Mult Scler 10(2):165\u2013169","journal-title":"Mult Scler"}],"container-title":["Molecular Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s12035-016-9893-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-016-9893-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-016-9893-3","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-016-9893-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T23:11:52Z","timestamp":1748905912000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s12035-016-9893-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,4,30]]},"references-count":70,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2017,7]]}},"alternative-id":["9893"],"URL":"https:\/\/doi.org\/10.1007\/s12035-016-9893-3","relation":{},"ISSN":["0893-7648","1559-1182"],"issn-type":[{"value":"0893-7648","type":"print"},{"value":"1559-1182","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4,30]]}}}