{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:04:58Z","timestamp":1789621498012,"version":"build-2803163510"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To explore the correlation of serum brain-derived neurotrophic factor (BDNF), matrix metalloproteinase-9 (MMP-9), and glutamate (Glu) changes with functional recovery after repetitive transcranial magnetic stimulation (rTMS) in acute ischemic stroke (AIS) patients, so as to provide biological evidence for rTMS efficacy evaluation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A retrospective study was conducted on 149 patients with AIS, who were assigned to a control group (\n                      <jats:italic>n<\/jats:italic>\n                      = 89, conventional comprehensive treatment) or an rTMS group (\n                      <jats:italic>n<\/jats:italic>\n                      = 60, combined rTMS intervention) based on their actual treatment, both for 4 weeks. The two groups were comparable at baseline in age (60.90 \u00b1 2.92 vs. 61.28 \u00b1 3.26 years), gender distribution (54 males vs. 40 males), and admission NIHSS scores [median (IQR): 10.0 (9.0\u201312.0) vs. 11.0 (9.0\u201312.0)] (all\n                      <jats:italic>P<\/jats:italic>\n                      &amp;gt; 0.05). In the rTMS group, rTMS was initiated within 72 h after stroke onset; the control group did not receive rTMS intervention. Serum levels of BDNF, MMP-9, and Glu were measured before and after treatment in both groups. Neurological and motor functions were assessed using the National Institutes of Health Stroke Scale (NIHSS) and the Fugl-Meyer Assessment (FMA). Pearson correlation was used to analyze the relationships between biomarker changes and functional improvements in the rTMS group, and adverse events were compared between groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      After 4 weeks, the rTMS group showed significantly greater increase in BDNF and decreases in MMP-9 and Glu than controls (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.05), along with lower NIHSS and higher FMA scores (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.05). Changes in all three biomarkers significantly correlated with NIHSS reduction and FMA improvement (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.001). Adverse events were similar between groups (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;gt; 0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>: rTMS combined with conventional therapy may be associated with greater improvement in neurological and motor function in AIS, potentially via regulating BDNF, MMP-9, and Glu. These biomarkers may serve as candidate indicators for treatment response. However, given the observational nature of this study, these findings should be interpreted with caution and require confirmation in future randomized controlled trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1907338","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:48:14Z","timestamp":1789620494000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Correlation analysis of serum brain-derived neurotrophic factor, matrix metalloproteinase-9, and glutamate levels changes after repetitive transcranial magnetic stimulation intervention with functional improvement in patients with acute ischemic stroke"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiaohui","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurology, Heji Hospital Affiliated to Changzhi Medical College","place":["Changzhi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Sui","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Unit, The Second Hospital of Dalian Medical University","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinru","family":"Han","sequence":"additional","affiliation":[{"name":"Changzhi Medical College","place":["Changzhi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Heji Hospital Affiliated to Changzhi Medical College","place":["Changzhi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyang","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Neurology, Heji Hospital Affiliated to Changzhi Medical College","place":["Changzhi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengjie","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of General Practice, The Second Hospital of Dalian Medical University","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e40223","DOI":"10.1097\/MD.0000000000040223","article-title":"Efficacy and safety of edaravone combined with Ginkgo leaf extract and dipyridamole in the treatment of acute cerebral infarction: a systematic review and meta-analysis","volume":"103","author":"Lyu","year":"2024","journal-title":"Medicine."},{"key":"B2","doi-asserted-by":"publisher","first-page":"S140","DOI":"10.5005\/jp-journals-10071-23192","article-title":"Acute ischemic stroke: management approach","volume":"23","author":"Chugh","year":"2019","journal-title":"Indian J Crit Care Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"e897","DOI":"10.1016\/S2468-2667(21)00228-0","article-title":"Temporal trend and attributable risk factors of stroke burden in China, 1990\u20132019: an analysis for the global burden of disease study 2019","volume":"6","author":"Ma","year":"2021","journal-title":"Lancet Public Health."},{"key":"B4","doi-asserted-by":"publisher","first-page":"L155","DOI":"10.1093\/eurheartj\/suaa157","article-title":"Time is brain: timing of revascularization of brain arteries in stroke","volume":"22","author":"Risitano","year":"2020","journal-title":"Eur Heart J Suppl"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e076161","DOI":"10.1136\/bmj-2023-076161","article-title":"Advances in treatments for acute ischemic stroke","volume":"389","author":"Sharma","year":"2025","journal-title":"BMJ."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2912","DOI":"10.1097\/CM9.0000000000002885","article-title":"Definition, prediction, prevention and management of patients with severe ischemic stroke and large infarction","volume":"136","author":"Hua","year":"2023","journal-title":"Chin Med J."},{"key":"B7","doi-asserted-by":"publisher","first-page":"296","DOI":"10.4103\/bc.bc_165_24","article-title":"Neuroprotective strategies in acute ischemic stroke: a narrative review of recent advances and clinical outcomes","volume":"10","author":"Zhao","year":"2024","journal-title":"Brain Circ."},{"key":"B8","doi-asserted-by":"publisher","first-page":"90","DOI":"10.22365\/jpsych.2021.054","article-title":"Advances in transcranial magnetic stimulation (TMS) and its applications in resistant depression","volume":"32","author":"Koutsomitros","year":"2021","journal-title":"Psychiatriki"},{"key":"B9","doi-asserted-by":"publisher","first-page":"106021","DOI":"10.1016\/j.neuint.2025.106021","article-title":"Repetitive transcranial magnetic stimulation as a universal modulator of synaptic plasticity: bridging the gap between functional and structural plasticity","volume":"188","author":"Popovic","year":"2025","journal-title":"Neurochem Int."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1487","DOI":"10.1007\/s10571-022-01264-x","article-title":"Repetitive transcranial magnetic stimulation of the brain after ischemic stroke: mechanisms from animal models","volume":"43","author":"Xing","year":"2023","journal-title":"Cell Mol Neurobiol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"e25358","DOI":"10.1002\/jnr.25358","article-title":"Effects of a novel regimen of repetitive transcranial magnetic stimulation (rTMS) on neural remodeling and motor function in adult male mice with ischemic stroke","volume":"102","author":"Peipei","year":"2024","journal-title":"J Neurosci Res."},{"key":"B12","doi-asserted-by":"publisher","first-page":"689","DOI":"10.3390\/neurolint16040052","article-title":"The effect of repetitive transcranial magnetic stimulation on cognition in diffuse axonal injury in a rat model","volume":"16","author":"Kim","year":"2024","journal-title":"Neurol Int."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1969482","DOI":"10.1155\/2020\/1969482","article-title":"Brain-derived neurotrophic factor and its potential therapeutic role in stroke comorbidities","volume":"2020","author":"Liu","year":"2020","journal-title":"Neural Plast."},{"key":"B14","doi-asserted-by":"publisher","first-page":"110192","DOI":"10.1016\/j.neuropharm.2024.110192","article-title":"Inhibition of matrix metalloproteinases to reduce blood brain barrier disruption and haemorrhagic transformation in ischaemic stroke: go broad or go narrow?","volume":"262","author":"Kawa","year":"2025","journal-title":"Neuropharmacology."},{"key":"B15","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1186\/s40001-026-04069-6","article-title":"Study on the expression changes and clinical significance of ICAM-1, MMP-9, and Gal-3 in patients with ischemic stroke","volume":"31","author":"Su","year":"2026","journal-title":"Eur J Med Res."},{"key":"B16","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.pneurobio.2013.11.006","article-title":"Excitotoxicity and stroke: identifying novel targets for neuroprotection","volume":"115","author":"Lai","year":"2014","journal-title":"Prog Neurobiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"115804","DOI":"10.1016\/j.bbr.2025.115804","article-title":"Neuroprotective role of GLT-1\/EAAT2 in glutamate-induced excitotoxicity","volume":"495","author":"Zhang","year":"2025","journal-title":"Behav Brain Res."},{"key":"B18","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.jphys.2013.12.012","article-title":"National Institutes of health stroke scale (NIHSS)","volume":"60","author":"Kwah","year":"2014","journal-title":"J Physiother."},{"key":"B19","doi-asserted-by":"publisher","first-page":"50","DOI":"10.3390\/jcdd10020050","article-title":"Effect of core exercises on motor function recovery in stroke survivors with very severe motor impairment","volume":"10","author":"Bacho","year":"2023","journal-title":"J Cardiovasc Dev Dis."},{"key":"B20","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1097\/01.JAA.0000000000000203","article-title":"Acute ischemic stroke: a guideline-based overview of evaluation and management","volume":"38","author":"Bogenschutz","year":"2025","journal-title":"JAAPA."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e0270096","DOI":"10.1371\/journal.pone.0270096","article-title":"Risk factors of dysphagia in patients with ischemic stroke: a meta-analysis and systematic review","volume":"17","author":"Yang","year":"2022","journal-title":"PLoS One."},{"key":"B22","doi-asserted-by":"publisher","first-page":"83","DOI":"10.3233\/NRE-201606","article-title":"Effects of coupling inhibitory and facilitatory repetitive transcranial magnetic stimulation on motor recovery in patients following acute cerebral infarction","volume":"48","author":"Chen","year":"2021","journal-title":"NeuroRehabilitation."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1177\/0269215517692386","article-title":"Short- and long-term effects of repetitive transcranial magnetic stimulation on upper limb motor function after stroke: a systematic review and meta-analysis","volume":"31","author":"Zhang","year":"2017","journal-title":"Clin Rehabil."},{"key":"B24","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/s12984-022-00999-4","article-title":"Effects of transcranial magnetic stimulation in modulating cortical excitability in patients with stroke: a systematic review and meta-analysis","volume":"19","author":"Bai","year":"2022","journal-title":"J Neuroeng Rehabil."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1124221","DOI":"10.3389\/fncir.2023.1124221","article-title":"Practice makes plasticity: 10-Hz rTMS enhances LTP-like plasticity in musicians and athletes","volume":"17","author":"Kweon","year":"2023","journal-title":"Front Neural Circuits."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1077218","DOI":"10.3389\/fnagi.2022.1077218","article-title":"Effect of rTMS intervention on upper limb motor function after stroke: a study based on fNIRS","volume":"14","author":"Ni","year":"2022","journal-title":"Front Aging Neurosci."},{"key":"B27","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1002\/ana.10848","article-title":"Influence of interhemispheric interactions on motor function in chronic stroke","volume":"55","author":"Murase","year":"2004","journal-title":"Ann Neurol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1318093","DOI":"10.1155\/2018\/1318093","article-title":"Aberrances of cortex excitability and connectivity underlying motor deficit in acute stroke","volume":"2018","author":"Du","year":"2018","journal-title":"Neural Plast."},{"key":"B29","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1016\/j.clinph.2020.02.003","article-title":"Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): an update (2014\u20132018)","volume":"131","author":"Lefaucheur","year":"2020","journal-title":"Clin Neurophysiol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"111338","DOI":"10.1016\/j.brainresbull.2025.111338","article-title":"Dysregulation of proBDNF\/p75NTR and BDNF\/TrkB signaling in acute ischemic stroke: different sides of the same coins","volume":"226","author":"Alnoaman","year":"2025","journal-title":"Brain Res Bull."},{"key":"B31","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1007\/s11481-019-09903-9","article-title":"Calycosin preserves BDNF\/TrkB signaling and reduces post-stroke neurological injury after cerebral ischemia by reducing accumulation of hypertrophic and TNF-\u03b1-containing microglia in rats","volume":"15","author":"Hsu","year":"2020","journal-title":"J Neuroimmune Pharmacol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1641","DOI":"10.1016\/j.brs.2025.08.019","article-title":"Repetitive magnetic stimulation induces plasticity of excitatory synapses through cooperative pre- and postsynaptic activity","volume":"18","author":"Galanis","year":"2025","journal-title":"Brain Stimul."},{"key":"B33","doi-asserted-by":"publisher","first-page":"457","DOI":"10.3389\/fphys.2017.00457","article-title":"Mechanism of action for rTMS: a working hypothesis based on animal studies","volume":"8","author":"Soundara Rajan","year":"2017","journal-title":"Front Physiol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/S0893-133X(00)00099-3","article-title":"Long-term repetitive transcranial magnetic stimulation increases the expression of brain-derived neurotrophic factor and cholecystokinin mRNA, but not neuropeptide tyrosine mRNA in specific areas of rat brain","volume":"23","author":"M\u00fcller","year":"2000","journal-title":"Neuropsychopharmacology."},{"key":"B35","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1055\/s-2006-931542","article-title":"High-frequency repetitive transcranial magnetic stimulation improves refractory depression by influencing catecholamine and brain-derived neurotrophic factors","volume":"39","author":"Yukimasa","year":"2006","journal-title":"Pharmacopsychiatry."},{"key":"B36","doi-asserted-by":"publisher","first-page":"157162","DOI":"10.1016\/j.phymed.2025.157162","article-title":"Protection against stroke-induced blood-brain barrier disruption by guanxinning injection and its active-component combination via TLR4\/NF-\u03baB\/MMP9-mediated neuroinflammation","volume":"147","author":"Fan","year":"2025","journal-title":"Phytomedicine."},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2013.203","article-title":"Hemorrhagic transformation after ischemic stroke in animals and humans","author":"Jickling","year":"2014","journal-title":"J Cereb Blood Flow Metab."},{"key":"B38","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.jstrokecerebrovasdis.2009.10.008","article-title":"Matrix metalloproteinase-9 as a marker for acute ischemic stroke: a systematic review","volume":"20","author":"Ramos-Fernandez","year":"2011","journal-title":"J Stroke Cerebrovasc Dis."},{"key":"B39","doi-asserted-by":"publisher","first-page":"111385","DOI":"10.1016\/j.brainresbull.2025.111385","article-title":"Transcranial magnetic stimulation through attenuating blood-spinal cord barrier disruption and reducing inflammatory response to improve motor function in rats with spinal cord injury","volume":"226","author":"Xu","year":"2025","journal-title":"Brain Res Bull."},{"key":"B40","doi-asserted-by":"publisher","first-page":"9381","DOI":"10.3390\/ijms23169381","article-title":"Excitatory synaptic transmission in ischemic stroke: a new outlet for classical neuroprotective strategies","volume":"23","author":"Wang","year":"2022","journal-title":"Int J Mol Sci."},{"key":"B41","doi-asserted-by":"publisher","first-page":"2506","DOI":"10.3390\/biomedicines12112506","article-title":"Harnessing brain plasticity: the therapeutic power of repetitive transcranial magnetic stimulation (rTMS) and theta burst stimulation (TBS) in neurotransmitter modulation, receptor dynamics, and neuroimaging for neurological innovations","volume":"12","author":"Sharbafshaaer","year":"2024","journal-title":"Biomedicines."},{"key":"B42","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1016\/j.brs.2021.03.016","article-title":"NMDA-receptor agonist reveals LTP-like properties of 10-Hz rTMS in the human motor cortex","volume":"14","author":"Brown","year":"2021","journal-title":"Brain Stimul."}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1907338\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:48:16Z","timestamp":1789620496000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1907338\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,17]]},"references-count":42,"alternative-id":["10.3389\/fneur.2026.1907338"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2026.1907338","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,17]]},"article-number":"1907338"}}