ArticleJournal of advanced research2026
Targeting the muscle-brain axis to improve post-stroke cognition via the FNDC5/irisin/BDNF pathway.
Article in Journal of advanced research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Spatiotemporal dynamics of the host-tumor metabolic interface: Implications for precision nutritional oncology.Genes & diseases · 2026Review
- Exercise and Productive Hippocampal Neurogenesis After Stroke: From Niche Remodeling to Cognitive Recovery.Brain sciences · 2026Review
- Engineered Brain-Targeted Exosomes Delivering FGF1 for Sustained Glycemic Regulation and Multitarget Neurovascular Protection in Diabetic Stroke.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Integrated Multiomics Analysis Reveals Manual Therapy Restores Autophagic Homeostasis via the AMPK/ULK1 Axis in Chronic Low Back Pain.Pain research & management · 2026Article
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14 authors.
Funding
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Abstract
introductionThe muscle-brain axis involving FNDC5/irisin/BDNF supports brain health and cognition. Stroke often causes hemiplegic muscle atrophy, which may disrupt this axis and impair cognition.
objectivesTo determine whether stroke-induced muscle atrophy disrupts the FNDC5/irisin/BDNF axis and contributes to post-stroke cognitive impairment (PSCI) in patients, cynomolgus monkeys and rats.
methodsWe conducted a cross-sectional study of stroke patients 3-6 months post-onset from outpatient (n = 24) and matched healthy controls from the community (n = 22). Cognitive function was assessed using the MoCA, TMT-A, TMT-B, and AVLT-H. Serum irisin was quantified using ELISA. Bilateral mid-thigh MRI scanning (mDIXON-QUANT) evaluated muscle cross-sectional area and fat fraction. Next, in stroke cynomolgus monkeys and rats, muscle atrophy, FNDC5/irisin/BDNF expression, and cognition were measured. Finally, we evaluated whether upregulation of the FNDC5/irisin/BDNF axis via physical exercise or peripheral irisin overexpression alleviated PSCI in rats.
resultsStroke patients exhibited a 6.5 % decrease in cross-sectional area (CSA) and a 13.6 % increase in fat fraction in the paretic thigh compared with the non-paretic side. Serum irisin levels dropped by 40 % compared to controls and were positively linked to paretic muscle CSA and cognitive function. In cynomolgus monkeys, paretic muscle CSA fell by 40 % at 12 weeks post-stroke, along with a notable decrease in PGC-1α and FNDC5 protein in atrophic muscle. These monkeys also exhibited a 50 % decrease in serum irisin levels, reduced hippocampal BDNF expression, and fewer immature neurons compared to sham-operated controls. Similarly, stroke rats demonstrated paretic muscle atrophy and suppression of the FNDC5/irisin/BDNF signaling pathway. Enhancing irisin via exercise or peripheral irisin overexpression significantly increased BDNF expression and immature neurons in the hippocampus of stroke rats, ultimately improving PSCI (all p < 0.05).
conclusionsHemiplegic muscle atrophy contributes to PSCI through the FNDC5/irisin/BDNF axis downregulation. Elevating irisin shows therapeutic potential for PSCI.
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