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Research Article: 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

Date Published: 2026-09-17

Abstract:
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. A retrospective study was conducted on 149 patients with AIS, who were assigned to a control group ( n = 89, conventional comprehensive treatment) or an rTMS group ( 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 ± 2.92 vs. 61.28 ± 3.26 years), gender distribution (54 males vs. 40 males), and admission NIHSS scores [median (IQR): 10.0 (9.0–12.0) vs. 11.0 (9.0–12.0)] (all P > 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. After 4 weeks, the rTMS group showed significantly greater increase in BDNF and decreases in MMP-9 and Glu than controls ( P < 0.05), along with lower NIHSS and higher FMA scores ( P < 0.05). Changes in all three biomarkers significantly correlated with NIHSS reduction and FMA improvement ( P < 0.001). Adverse events were similar between groups ( P > 0.05). : 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.

Introduction:
Acute ischemic stroke (AIS) accounts for approximately 70% of all strokes and is characterized by rapid onset and progression, often resulting in debilitating neurological deficits such as hemiplegia, aphasia, and cognitive decline that profoundly impair patients' quality of life and impose substantial burdens on families and society ( 1 – 3 ). Current standard management includes time-windowed intravenous thrombolysis, endovascular recanalization, and pharmacotherapies (e.g., antiplatelet, anticoagulant, and…

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