{"title":"L-3n-butylphthalide maintains BBB permeability and attenuates cerebral ischemia-reperfusion injury in rats by increasing PGC-1<i>α</i> levels.","authors":"Yu Wang, Xiangsong Shi, Liling Wu, Hongfu Tian","doi":"10.1080/00207454.2025.2545534","DOIUrl":null,"url":null,"abstract":"<p><strong>Aim: </strong>The aim of the present study was to investigate the possible mechanisms of DL-3-n-butylphthalide (NBP) in maintaining the stability of the blood-brain barrier (BBB) and attenuating cerebral ischemia-reperfusion injury (CIRI) by increasing the levels of PGC-1<i>α</i>.</p><p><strong>Methods: </strong>A model of middle cerebral artery occlusion/reperfusion (MCAO/R) injury was established using Sprague-Dawley rats. The rats were divided into sham, MCAO/R, NBP, Vehicle and SR-18292 groups. 2,3,5-Triphenyltetrazolium chloride staining, hematoxylin and eosin (H&E) staining, and Evans Blue staining were performed to observe the volume of cerebral infarction, status of pathological injury, and BBB permeability of the brain tissue, respectively. Immunofluorescence staining and western blot analysis were performed to evaluate the expression of vascular endothelial cell markers (vWF and CD31), tight junction (TJ) protein markers (claudin5 and occludin), and PGC-1<i>α</i>.</p><p><strong>Results: </strong>H&E staining showed that the brain tissues of MCAO/R rats showed worsening vacuolar degeneration and necrosis. NBP reduced infarct volume, decreased the level of BBB extravasation, increased vascular density, and promoted the expression of TJs. Concurrently, NBP activated PGC-1<i>α</i> levels in rats subjected to MCAO/R. Downregulation of PGC-1<i>α</i> levels by PGC-1<i>α</i> inhibitors (SR-18292) could promote BBB permeability, infarct volume, and neurological deficits in the MCAO/R model.</p><p><strong>Conclusions: </strong>The present study demonstrates that NBP plays a role in maintaining the stability of the BBB and attenuates CIRI by increasing PGC-1<i>α</i> levels as well as by increasing the levels of vascular endothelial cells and TJ markers.</p>","PeriodicalId":14161,"journal":{"name":"International Journal of Neuroscience","volume":" ","pages":"1-12"},"PeriodicalIF":1.5000,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/00207454.2025.2545534","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Aim: The aim of the present study was to investigate the possible mechanisms of DL-3-n-butylphthalide (NBP) in maintaining the stability of the blood-brain barrier (BBB) and attenuating cerebral ischemia-reperfusion injury (CIRI) by increasing the levels of PGC-1α.
Methods: A model of middle cerebral artery occlusion/reperfusion (MCAO/R) injury was established using Sprague-Dawley rats. The rats were divided into sham, MCAO/R, NBP, Vehicle and SR-18292 groups. 2,3,5-Triphenyltetrazolium chloride staining, hematoxylin and eosin (H&E) staining, and Evans Blue staining were performed to observe the volume of cerebral infarction, status of pathological injury, and BBB permeability of the brain tissue, respectively. Immunofluorescence staining and western blot analysis were performed to evaluate the expression of vascular endothelial cell markers (vWF and CD31), tight junction (TJ) protein markers (claudin5 and occludin), and PGC-1α.
Results: H&E staining showed that the brain tissues of MCAO/R rats showed worsening vacuolar degeneration and necrosis. NBP reduced infarct volume, decreased the level of BBB extravasation, increased vascular density, and promoted the expression of TJs. Concurrently, NBP activated PGC-1α levels in rats subjected to MCAO/R. Downregulation of PGC-1α levels by PGC-1α inhibitors (SR-18292) could promote BBB permeability, infarct volume, and neurological deficits in the MCAO/R model.
Conclusions: The present study demonstrates that NBP plays a role in maintaining the stability of the BBB and attenuates CIRI by increasing PGC-1α levels as well as by increasing the levels of vascular endothelial cells and TJ markers.
期刊介绍：
The International Journal of Neuroscience publishes original research articles, reviews, brief scientific reports, case studies, letters to the editor and book reviews concerned with problems of the nervous system and related clinical studies, epidemiology, neuropathology, medical and surgical treatment options and outcomes, neuropsychology and other topics related to the research and care of persons with neurologic disorders. The focus of the journal is clinical and transitional research. Topics covered include but are not limited to: ALS, ataxia, autism, brain tumors, child neurology, demyelinating diseases, epilepsy, genetics, headache, lysosomal storage disease, mitochondrial dysfunction, movement disorders, multiple sclerosis, myopathy, neurodegenerative diseases, neuromuscular disorders, neuropharmacology, neuropsychiatry, neuropsychology, pain, sleep disorders, stroke, and other areas related to the neurosciences.
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