{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T17:15:22Z","timestamp":1793121322114,"version":"4.5.0"},"reference-count":118,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:p>Stroke significantly impacts mortality and long-term disability, necessitating effective rehabilitation strategies to enhance recovery. This review examines the roles of vagus nerve stimulation (VNS) and fastigial nucleus stimulation (FNS) in facilitating ischemic stroke recovery through brain-body interactions. VNS enhances ischemic stroke recovery by reprogramming microglia from proinflammatory (M1) to neuroprotective (M2) phenotypes, reducing neuroinflammation and promoting tissue repair via neurotrophic factors. It has shown promise in clinically improving chronic upper limb deficits when combined with rehabilitation therapies. Conversely, FNS provides cerebellar-mediated neuroprotection by mainly mitigating excitotoxic damage and inflammatory responses independent of cerebral blood flow alterations, as evidenced by preclinical models of middle cerebral artery occlusion. By integrating VNS-driven immunomodulation with FNS-mediated excitotoxicity suppression, this review highlights their synergistic potential to improve rehabilitation outcomes for ischemic stroke survivors. Biomarker-guided protocols: VNS for cortical\/subcortical ischemic deficits and FNS for cerebellar network recovery are advocated to address postischemic disability via anti-inflammatory rewiring, neuroplasticity enhancement, and cerebellar-thalamocortical circuit stabilization. Critical gaps remain in hemorrhagic stroke, where FNS\u2019s excitotoxicity suppression may destabilize clots, necessitating subtype-specific safety validations.<\/jats:p>","DOI":"10.1161\/strokeaha.125.051470","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T05:00:22Z","timestamp":1750827622000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":17,"title":["Brain-Body Interactions in Ischemic Stroke: VNS Reprograms Microglia and FNS Enhances Cerebellar Neuroprotection"],"prefix":"10.1161","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2858-3634","authenticated-orcid":true,"given":"Yuchun","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Rehabilitation Medicine, Huashan Hospital, Institute of Science and Technology for Brain-inspired Intelligence (ISTBI), Fudan University, Shanghai, China (Y.W., M.J.W., M.G., N.W., S.X.)."},{"name":"National Center for Neurological Disorders, Shanghai, China (Y.W., N.W.)."},{"name":"National Clinical Research Center for Geriatric Diseases, Shanghai, China (Y.W., N.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Yang","sequence":"additional","affiliation":[{"name":"Shanghai Sunshine Rehabilitation Center, Shanghai YangZhi Rehabilitation Hospital, Tongji University, China (Z.Y.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4480-1473","authenticated-orcid":true,"given":"Jinling","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Huashan Hospital, Institute of Science and Technology for Brain-inspired Intelligence (ISTBI), Fudan University, Shanghai, China (Y.W., M.J.W., M.G., N.W., S.X.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1918-0138","authenticated-orcid":true,"given":"Minyan","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Huashan Hospital, Institute of Science and Technology for Brain-inspired Intelligence (ISTBI), Fudan University, Shanghai, China (Y.W., M.J.W., M.G., N.W., S.X.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3482-7327","authenticated-orcid":true,"given":"Nianhong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Huashan Hospital, Institute of Science and Technology for Brain-inspired Intelligence (ISTBI), Fudan University, Shanghai, China (Y.W., M.J.W., M.G., N.W., S.X.)."},{"name":"National Center for Neurological Disorders, Shanghai, China (Y.W., N.W.)."},{"name":"National Clinical Research Center for Geriatric Diseases, Shanghai, China (Y.W., N.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2062-0226","authenticated-orcid":true,"given":"Shumao","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Huashan Hospital, Institute of Science and Technology for Brain-inspired Intelligence (ISTBI), Fudan University, Shanghai, China (Y.W., M.J.W., M.G., N.W., S.X.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-022-00703-z"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac129"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02507-0"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-021-00542-4"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000012803"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.121.035425"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)01410-7"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2016.5823"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2015.240"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000182100.65262.46"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1713973"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.123.044226"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.09.018"},{"key":"e_1_3_2_15_2","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/B978-0-443-22268-9.00015-6","volume-title":"Brain and Organ Communication","author":"Sarvottam K","year":"2025","unstructured":"Sarvottam K, Gajbhiye RN, Arvind A, Yadav BS. Crosstalk between brain and the peripheral tissues. In: David Todd R, Ahmad MM, ed. Brain and Organ Communication. Elsevier; 2025:273\u2013294."},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvaa151"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-022-00678-w"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-024-00953-z"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11910-023-01323-w"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2024.51217"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brs.2021.12.004"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-022-01318-4"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.123.043414"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2021.102909"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2024.1527842"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1113\/JP287099"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2022.136860"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.04.022"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brs.2024.05.005"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvae167"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.7870"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.3390\/medicina60122061"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01688-x"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/cns.12288"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202417449"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02501-2"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.107645"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000005015"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12030753"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2021.108654"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-021-00904-7"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-52654-2"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.123.044279"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.123.030539"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2023.09.036"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-022-01464-7"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.08.050"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202216269"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202307971"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-024-01767-4"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2022.06.017"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2021.02.049"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.121.319994"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2024.1334887"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-025-10288-7"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.815347"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-021-00507-y"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-06234-9"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2021.04.018"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10050953"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1186\/s41232-022-00193-y"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00670-9"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-022-00562-y"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-819410-2.00016-3"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2022.153980"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11081"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2004.12.006"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2016.05.017"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.7b00965"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.77455"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2020.120645"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-024-05091-0"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.112030"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.117337"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-023-03512-7"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2023.106758"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114991"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.2174\/0118746098369369250119112935"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202400149"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2024.114920"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14690"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awae026"},{"key":"e_1_3_2_83_2","doi-asserted-by":"publisher","DOI":"10.2174\/0115672050306008240321034006"},{"key":"e_1_3_2_84_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2024.110726"},{"key":"e_1_3_2_85_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2006.05.011"},{"key":"e_1_3_2_86_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2017.00076"},{"key":"e_1_3_2_87_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-022-00852-6"},{"key":"e_1_3_2_88_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2020.04.011"},{"key":"e_1_3_2_89_2","doi-asserted-by":"publisher","DOI":"10.1159\/000543513"},{"key":"e_1_3_2_90_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11571-024-10143-8"},{"key":"e_1_3_2_91_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11910-023-01319-6"},{"key":"e_1_3_2_92_2","doi-asserted-by":"publisher","DOI":"10.1111\/wrr.13151"},{"key":"e_1_3_2_93_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10286-024-01065-w"},{"key":"e_1_3_2_94_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brs.2017.07.013"},{"key":"e_1_3_2_95_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-25864-1"},{"key":"e_1_3_2_96_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2020.568051"},{"key":"e_1_3_2_97_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brs.2023.06.006"},{"key":"e_1_3_2_98_2","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202010674"},{"key":"e_1_3_2_99_2","unstructured":"McDonald K. Cognition Neuroelectric Brain Function and Salivary Biomarkers Following Exercise. Northeastern University; 2023."},{"key":"e_1_3_2_100_2","first-page":"172","article-title":"Magnetic resonance imaging demonstrates that electric stimulation of cerebellar fastigial nucleus reduces cerebral infarction in rats.","volume":"21","author":"Berger S","year":"1990","unstructured":"Berger S, Ballon D, Graham M, Underwood M, Khayata M, Leggiero R, Koutcher J, Reis D. Magnetic resonance imaging demonstrates that electric stimulation of cerebellar fastigial nucleus reduces cerebral infarction in rats. Stroke. 1990;21:172\u2013176. http:\/\/intl-stroke.ahajournals.org\/cgi\/content\/abstract\/21\/11\/III172","journal-title":"Stroke"},{"key":"e_1_3_2_101_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws194"},{"key":"e_1_3_2_102_2","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X21666230824091601"},{"key":"e_1_3_2_103_2","doi-asserted-by":"crossref","first-page":"1820","DOI":"10.1038\/s42255-023-00890-z","article-title":"Spatially resolved metabolomics and isotope tracing reveal dynamic metabolic responses of dentate granule neurons with acute stimulation.","volume":"5","author":"Miller A","year":"2023","unstructured":"Miller A, York EM, Stopka SA, Mart\u00ednez-Fran\u00e7ois JR, Hossain MA, Baquer G, Regan MS, Agar NY, Yellen G. Spatially resolved metabolomics and isotope tracing reveal dynamic metabolic responses of dentate granule neurons with acute stimulation. Nat Metabol. 2023;5:1820\u20131835.","journal-title":"Nat Metabol"},{"key":"e_1_3_2_104_2","doi-asserted-by":"publisher","DOI":"10.1111\/cns.12383"},{"key":"e_1_3_2_105_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-53891-1"},{"key":"e_1_3_2_106_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-50166-7"},{"key":"e_1_3_2_107_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-023-00775-0"},{"key":"e_1_3_2_108_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2024.107413"},{"key":"e_1_3_2_109_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00406-017-0794-x"},{"key":"e_1_3_2_110_2","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202303267"},{"key":"e_1_3_2_111_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2024.1396789"},{"key":"e_1_3_2_112_2","doi-asserted-by":"publisher","DOI":"10.1080\/15257770.2022.2098974"},{"key":"e_1_3_2_113_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27113607"},{"key":"e_1_3_2_114_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2022.101588"},{"key":"e_1_3_2_115_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13040624"},{"key":"e_1_3_2_116_2","doi-asserted-by":"publisher","DOI":"10.1159\/000430233"},{"key":"e_1_3_2_117_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2004.11.013"},{"key":"e_1_3_2_118_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.03.019"},{"key":"e_1_3_2_119_2","doi-asserted-by":"publisher","DOI":"10.1177\/1545968318804425"}],"container-title":["Stroke"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/STROKEAHA.125.051470","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T18:00:40Z","timestamp":1758564040000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/STROKEAHA.125.051470"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":118,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1161\/STROKEAHA.125.051470"],"URL":"https:\/\/doi.org\/10.1161\/strokeaha.125.051470","relation":{},"ISSN":["0039-2499","1524-4628"],"issn-type":[{"value":"0039-2499","type":"print"},{"value":"1524-4628","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"2025-06-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}