{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T04:07:44Z","timestamp":1778645264210,"version":"3.51.4"},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,5,18]],"date-time":"2025-05-18T00:00:00Z","timestamp":1747526400000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82201488"],"award-info":[{"award-number":["82201488"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Guillain\u2012Barr\u00e9 syndrome (GBS) is an immune\u2010mediated peripheral neuropathy in which inflammatory cells and cytokines participate. The JAK\u2010STAT signaling pathway is a major pathway involved in cytokine signal transduction, but the role of this pathway in GBS is not clear. AG490 is a tyrosine kinase inhibitor that specifically inhibits JAK2 activity and downregulates STAT3 phosphorylation. The aim of this study was to investigate the function of the JAK2\/STAT3 pathway in a rat model of experimental autoimmune neuritis (EAN).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Lewis rats were divided into three groups: the control, the EAN, and the AG490 groups. The EAN and AG490 groups were immunized with P2 peptide to create the EAN models, while the control group received an equal volume of vehicle solution without P2 peptide. Starting from Day 5 post\u2010immunization (PI), the AG490 group was administered AG490 (10\u00a0mg\/kg) every other day, while the control and EAN groups received an equal volume of vehicle solution without AG490. All rats were weighed and evaluated according to the EAN function score (1\u201310) by two investigators. Rats were sacrificed on Day 16 PI, and the sciatic nerves were examined by light microscopy, indirect immunohistochemistry, and western blotting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>AG490\u2010treated rats had improved clinical scores compared with those of EAN rats. Hematoxylin and eosin (H&amp;E) and CD45 staining showed significant inflammatory infiltration of the sciatic nerve in the EAN group compared with the control group, and demonstrated reduced inflammatory infiltration in the AG490 group. Luxol fast blue (LFB) staining showed a reduction of myelin loss in the AG490 group compared with the EAN group. The levels of TGF\u2010\u03b21, IFN\u2010\u03b3, and IL\u20106 increased in the EAN group and showed a significant decrease in rats treated with AG490. The JAK2\u2010STAT3 signaling pathway was activated in EAN rats, and the AG490 group showed decreased expression levels of JAK2, p\u2010JAK2, and p\u2010STAT3 compared with those of the EAN group. Immunofluorescence also showed a decrease in the levels of p\u2010JAK2 and p\u2010STAT3 in the sciatic nerve of EAN rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The JAK2\/STAT3 signaling pathway is involved in the pathogenesis of EAN, and inhibition of this pathway can reduce the inflammatory response in EAN rats. Despite the limitations in extrapolating EAN findings to human GBS, this study provided new insights into the pathogenesis and potential therapeutic targets of human GBS.<\/jats:p><\/jats:sec>","DOI":"10.1002\/brb3.70566","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T06:39:10Z","timestamp":1747636750000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Experimental Autoimmune Neuritis Nerve Demyelination Is Attenuated by Blocking JAK2\/STAT3 Signaling Pathway in Rats"],"prefix":"10.1002","volume":"15","author":[{"given":"Rumeng","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Neurology Renmin Hospital of Wuhan University  Wuhan Hubei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuping","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology Renmin Hospital of Wuhan University  Wuhan Hubei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology Renmin Hospital of Wuhan University  Wuhan Hubei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology Renmin Hospital of Wuhan University  Wuhan Hubei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Neurology Renmin Hospital of Wuhan University  Wuhan Hubei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiajia","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Neurology Renmin Hospital of Wuhan University  Wuhan Hubei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4017-4529","authenticated-orcid":false,"given":"Zuneng","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Neurology Renmin Hospital of Wuhan University  Wuhan Hubei China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,5,18]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410410302"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-017-0701-9"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00988"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/268752a0"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2016.07.013"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.64.2.162"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2018.08.001"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.1999.00808.x"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.4161\/jkst.24134"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1006\/clin.1998.4573"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/08916930701356846"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(98)00053-8"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.1023177"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4889(02)00325-7"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.154686"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-019-01880-6"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.24.021605.090737"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1095-7"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/00207454.2020.1725511"},{"issue":"2","key":"e_1_2_11_21_1","first-page":"165","article-title":"Expression of Intracellular Transforming Growth Factor\u2010beta1 in CD4+CD25+ Cells in Patients With Systemic Lupus Erythematosus","volume":"41","author":"Lu L. 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