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<p>Remote ischemic preconditioning (RIpreC) is a strategy for remotely protecting target organs such as the brain by applying brief ischemia and reperfusion to the limb. However, the mechanisms underlying RIpreC-induced neuroprotection remain unclear. We aimed to investigate the neuroprotective effects of RIpreC on the peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α)/ fibronectin type III domain-containing protein 5 (FNDC5)/ brain-derived neurotrophic factor (BDNF) pathway in rat models of ischemic stroke. Rats were assigned to three groups: ischemia-reperfusion injury (IR, <i>n</i> = 11), RIpreC and IR (RIpreC, <i>n</i> = 11), and intact control (control, <i>n</i> = 5). RIpreC was performed approximately 24&#xa0;h before IR injury. IR injury induced by middle cerebral artery occlusion (MCAO) for 60&#xa0;min. At 2 days after MCAO, brain infarction, sensorimotor functions, and the expression of PGC-1α, FNDC5/irisin, BDNF, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3, terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick end labeling (TUNEL)-positive cells, and the p-Akt/Akt ratio were examined. In addition, SR-18,292, a PGC-1α inhibitor, was administered 1&#xa0;h before MCAO. The RIpreC group had a significantly reduced infarct volume and ameliorated sensorimotor function compared with the IR group. RIpreC increased the expression of PGC-1α, FNDC5, BDNF, and the p-Akt/Akt ratio in the ischemic brain. Bax/Bcl-2 ratios, as well as perilesional caspase-3- and TUNEL-positive neuronal cells, decreased following RIpreC. Inhibition of PGC-1α blunted the RIpreC-induced neuroprotective and neurorestorative effects. This study suggests that RIpreC induced BDNF expression through a PGC-1α/FNDC5 pathway after ischemic stroke, thereby exerting neuroprotection and ameliorating post-stroke neurobehavioral dysfunctions.</p>

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Remote Ischemic Preconditioning Exerts Neuroprotective Effects Via the PGC-1α/FNDC5/BDNF Pathway in Focal Brain Ischemia of Rats

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月9日

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  • Teruki Matsuoka,
  • Ryoma Matsuzaki,
  • Kazuki Nakanishi,
  • Shogo Kakimoto,
  • Yuki Kato,
  • Shotaro Otsuka,
  • Kiyoshi Kikuchi,
  • Harutoshi Sakakima

摘要

Remote ischemic preconditioning (RIpreC) is a strategy for remotely protecting target organs such as the brain by applying brief ischemia and reperfusion to the limb. However, the mechanisms underlying RIpreC-induced neuroprotection remain unclear. We aimed to investigate the neuroprotective effects of RIpreC on the peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α)/ fibronectin type III domain-containing protein 5 (FNDC5)/ brain-derived neurotrophic factor (BDNF) pathway in rat models of ischemic stroke. Rats were assigned to three groups: ischemia-reperfusion injury (IR, n = 11), RIpreC and IR (RIpreC, n = 11), and intact control (control, n = 5). RIpreC was performed approximately 24 h before IR injury. IR injury induced by middle cerebral artery occlusion (MCAO) for 60 min. At 2 days after MCAO, brain infarction, sensorimotor functions, and the expression of PGC-1α, FNDC5/irisin, BDNF, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3, terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick end labeling (TUNEL)-positive cells, and the p-Akt/Akt ratio were examined. In addition, SR-18,292, a PGC-1α inhibitor, was administered 1 h before MCAO. The RIpreC group had a significantly reduced infarct volume and ameliorated sensorimotor function compared with the IR group. RIpreC increased the expression of PGC-1α, FNDC5, BDNF, and the p-Akt/Akt ratio in the ischemic brain. Bax/Bcl-2 ratios, as well as perilesional caspase-3- and TUNEL-positive neuronal cells, decreased following RIpreC. Inhibition of PGC-1α blunted the RIpreC-induced neuroprotective and neurorestorative effects. This study suggests that RIpreC induced BDNF expression through a PGC-1α/FNDC5 pathway after ischemic stroke, thereby exerting neuroprotection and ameliorating post-stroke neurobehavioral dysfunctions.