Naringenin Protected Against Blood Brain Barrier Breakdown after Ischemic Stroke through GSK-3β/ β-Catenin Pathway.

Autor: Yang Y; Department of Pharmacy, The First Affiliated Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, China., Li L; Department of Neurosurgery, The First Affiliated Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, China., Yu L; Department of Information, The First Affiliated Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, China., Xia Y; Department of Gastroenterology, The First Affiliated Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, China., Fang Z; Department of Critical Case Medicine, Translational Research Institute of Brain and Brain-Like intelligence, Fourth People's Hospital, Tongji University, Shanghai, 200434, China. zongping03@163.com., Wang S; Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital, The Fourth military Medical University, Xi'an, Shaanxi, 710032, China. wangshiquan-301@163.com.
Jazyk: angličtina
Zdroj: Neurochemical research [Neurochem Res] 2024 Nov 18; Vol. 50 (1), pp. 17. Date of Electronic Publication: 2024 Nov 18.
DOI: 10.1007/s11064-024-04259-w
Abstrakt: Protection against blood-brain barrier (BBB) dysfunction is key to reduce the cerebral ischemia injury as its breakdown causes edema formation and extravasation of blood components and immune cells. The maintenance of BBB integrity requires the GSK-3β/β-catenin pathway activity. Naringenin (NAR), an effective monomer from Chinese herbal medicine, had potent protective effect on brain inflammatory and oxidative injury. However, whether NAR could protect the integrity of BBB during cerebral ischemia injury and the involvement of GSK-3β/β-catenin pathway in the beneficial effect of NAR was unknown. Therefore, mouse middle cerebral artery occlusion/reperfusion (IR) model was employed to answer these questions. NAR was intraperitoneally administrated once daily for 6 days immediately after IR with the dose of 10 mg/kg. BBB damage was evaluated with Evans blue. Protein levels of GSK-3β and β-catenin in vascular endothelial cells at penumbra were assessed with western blotting and immunofluorescence. The experimental data suggested that NAR improved neurological deficits, decreased the percentage of infarct volumes and neuronal apoptosis at 7d after IR. NAR improved BBB damage as evidenced by a lower permeability of Evans blue dye and upregulation of tight junction proteins such as zonula occludens-1(ZO-1), Occludin and Claudin-5. Importantly, GSK-3β/β-catenin pathway activity was related to the improvement of BBB integrity rendered by NAR. Our findings demonstrated that NAR might become a potential therapeutic drug for IR.
Competing Interests: Declarations Competing Interests The authors declare no competing interests.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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