{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T10:12:35Z","timestamp":1788862355853,"version":"build-2803163510"},"reference-count":72,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuroprotection"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Neuromodulation therapy has emerged as a potential brain cytoprotective strategy in the hyperacute phase of ischemic stroke (IS). This systematic review aimed to evaluate the cytoprotective effects of neuromodulation in animal models of IS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic search of the MEDLINE, Embase, and LILACS databases was conducted to identify in vivo preclinical studies that investigated noninvasive or minimally invasive neuromodulation therapy administered within 24\u2009h of arterial occlusion and included a control group. The primary outcome was infarct volume, and the secondary outcomes included assessments of neurological function using validated behavioral scales. Random\u2010effects meta\u2010analyses were performed for all outcomes using the Cochrane Review Manager software (version 5.4.1). The protocol was prospectively registered in the International Prospective Register of Systematic Reviews database (No. CRD42020165347).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Thirty studies were included in the qualitative synthesis (2347 reported animals), and 25 studies were eligible for meta\u2010analysis. Most studies employed middle cerebral artery occlusion models. Neuromodulation techniques included electroacupuncture, repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and vagus nerve stimulation. Pooled analyses demonstrated that neuromodulation significantly reduced infarct volume both in absolute (standardized mean difference [SMD]: \u22120.80;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and relative terms (SMD: \u22122.01;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and improved neurological outcomes (SMD: \u22121.53;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.006). However, considerable heterogeneity was observed across studies and interventions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Neuromodulation confers brain cytoprotective effects in experimental IS models; however, the high heterogeneity in stimulation parameters and outcomes limits its translational potential. Standardization of experimental protocols and reporting is required to improve reproducibility.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/nep3.70056","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T09:29:40Z","timestamp":1788859780000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Noninvasive or minimally invasive neuromodulation in animal models of acute ischemic stroke: A systematic review and meta\u2010analysis"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0309-2225","authenticated-orcid":false,"given":"Igor Caitano","family":"Salles","sequence":"first","affiliation":[{"name":"Department of Neurology Clinical Hospital of the University of Sao Paulo Medical School Sao Paulo Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateus Paquesse","family":"Pellegrino","sequence":"additional","affiliation":[{"name":"Radiology Institute, Clinical Hospital of the University of Sao Paulo Medical School Sao Paulo Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica Borges","family":"Kroth","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy Syrian Lebanese Hospital Sao Paulo Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara Lucato","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Department of Evidence\u2010Based Medicine Brazilian Medical Association Sao Paulo Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca Schiliro","family":"Tristao","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Faculty of Medicine of ABC Santo Andre Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jullyanna Sabrysna Morais","family":"Shinosaki","sequence":"additional","affiliation":[{"name":"Department of Neurology Clinical Hospital of the Federal University of Uberlandia Uberlandia Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanderley Marques","family":"Bernardo","sequence":"additional","affiliation":[{"name":"Department of Evidence\u2010Based Medicine Brazilian Medical Association Sao Paulo Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana Bastos","family":"Conforto","sequence":"additional","affiliation":[{"name":"Radiology Institute, Clinical Hospital of the University of Sao Paulo Medical School Sao Paulo Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"issue":"10","key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/S1474-4422(24)00369-7","article-title":"Global, regional, and 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