Gut-Brain Axis Mediated Mechanisms of SGLT-2Inhibitors in Enhancing Neural Repair after Ischemic Stroke

Ni MAO; Xiaoling WANG; Yanzhao ZHAI; Lei ZHANG

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Ni MAO, Xiaoling WANG, Yanzhao ZHAI, Lei ZHANG. Gut-Brain Axis Mediated Mechanisms of SGLT-2Inhibitors in Enhancing Neural Repair after Ischemic Stroke[J]. Journal of Kunming Medical University.

Citation:

Ni MAO, Xiaoling WANG, Yanzhao ZHAI, Lei ZHANG. Gut-Brain Axis Mediated Mechanisms of SGLT-2Inhibitors in Enhancing Neural Repair after Ischemic Stroke[J]. Journal of Kunming Medical University.

Ni MAO, Xiaoling WANG, Yanzhao ZHAI, Lei ZHANG. Gut-Brain Axis Mediated Mechanisms of SGLT-2Inhibitors in Enhancing Neural Repair after Ischemic Stroke[J]. Journal of Kunming Medical University.

Citation:

Ni MAO, Xiaoling WANG, Yanzhao ZHAI, Lei ZHANG. Gut-Brain Axis Mediated Mechanisms of SGLT-2Inhibitors in Enhancing Neural Repair after Ischemic Stroke[J]. Journal of Kunming Medical University.

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Gut-Brain Axis Mediated Mechanisms of SGLT-2Inhibitors in Enhancing Neural Repair after Ischemic Stroke

1.
Department of Neurology，The 960th Hospital of the Joint Logistics Support Force of PLA，Jinan Shandong 250000
2.
Department of Neurology，Jinan Central Hospital，Jinan Shandong 250013，China

Received Date: 2025-07-25

Abstract

Abstract

Objective To investigate the neuroprotective effects and underlying mechanisms of dapagliflozin （DAP） in a rat model of ischemic stroke （IS） induced by middle cerebral artery occlusion （MCAO）. Methods The MCAO model was established and rats were randomly assigned to the sham, model, and DAP groups （n = 10）. DAP （1 mg/kg·d） was administered by gavage 2 h after reperfusion for 7 consecutive days. Neurological function was assessed using the modified neurological severity score （mNSS）. Infarct volume, brain water content, and hippocampal neuronal apoptosis were measured. Gut microbiota composition was analyzed by 16S rRNA sequencing. Serum levels of NGF, BDNF, D-lactate, DAO, and inflammatory cytokines were determined by ELISA. Protein expression of ZO-1, Occludin, Claudin-1, cleaved Caspase-3, HMGB1, RAGE, NF-κB, and p-NF-κB was detected by Western blot. Results Compared with the model group, DAP significantly reduced mNSS scores, （P < 0.01） infarct volume, brain water content, and neuronal apoptosis （ P < 0.01）. 16S rRNA sequencing revealed increased abundances of Lactobacillus and Bifidobacterium, and decreased Enterobacter in the DAP group, which were significantly correlated with mNSS scores （P < 0.001）. DAP increased serum NGF and BDNF levels, while reducing D-lactate, DAO, and inflammatory cytokines （all P < 0.01）. Western blot showed that DAP upregulated ZO-1, Occludin, and Claudin-1, while downregulating cleaved Caspase-3, HMGB1, RAGE, NF-κB, and p-NF-κB （all P < 0.01）. Conclusion DAP can improve neurological function and brain injury in MCAO rats by inhibiting apoptosis and inflammation and regulating intestinal flora.
- Ischemic Stroke,
- Dapagliflozin,
- Gut–brain Axis,
- Gut Microbiota,
- Neuroprotection

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References(28)

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