دورية أكاديمية
أعرض في EDS

Investigating the therapeutic effects of nimodipine on vasogenic cerebral edema and blood-brain barrier impairment in an ischemic stroke rat model.

التفاصيل البيبلوغرافية
العنوان: Investigating the therapeutic effects of nimodipine on vasogenic cerebral edema and blood-brain barrier impairment in an ischemic stroke rat model.
المؤلفون: Shadman J; Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences, Ardabil, Iran., Panahpour H; Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences, Ardabil, Iran. Electronic address: panahpour.h@gmail.com., Alipour MR; Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: alipourmr@tbzmed.ac.ir., Salimi A; Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran., Shahabi P; Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Azar SS; Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.
المصدر: Neuropharmacology [Neuropharmacology] 2024 Oct 01; Vol. 257, pp. 110054. Date of Electronic Publication: 2024 Jun 29.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Pergamon Press Country of Publication: England NLM ID: 0236217 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-7064 (Electronic) Linking ISSN: 00283908 NLM ISO Abbreviation: Neuropharmacology Subsets: MEDLINE
أسماء مطبوعة: Publication: Oxford : Pergamon Press
Original Publication: Oxford, New York, Pergamon.
مواضيع طبية MeSH: Nimodipine*/pharmacology , Brain Edema*/drug therapy , Brain Edema*/etiology , Brain Edema*/metabolism , Blood-Brain Barrier*/drug effects , Blood-Brain Barrier*/metabolism , Ischemic Stroke*/drug therapy , Ischemic Stroke*/metabolism , Matrix Metalloproteinase 9*/metabolism , Calcium Channel Blockers*/pharmacology, Animals ; Male ; Rats ; Disease Models, Animal ; Reactive Oxygen Species/metabolism ; Membrane Potential, Mitochondrial/drug effects ; Rats, Sprague-Dawley ; Intercellular Adhesion Molecule-1/metabolism ; Infarction, Middle Cerebral Artery/drug therapy ; Infarction, Middle Cerebral Artery/complications ; Mitochondrial Swelling/drug effects ; Succinate Dehydrogenase/metabolism
مستخلص: Vasogenic brain edema, a potentially life-threatening consequence following an acute ischemic stroke, is a major clinical problem. This research aims to explore the therapeutic benefits of nimodipine, a calcium channel blocker, in mitigating vasogenic cerebral edema and preserving blood-brain barrier (BBB) function in an ischemic stroke rat model. In this research, animals underwent the induction of ischemic stroke via a 60-min blockage of the middle cerebral artery and treated with a nonhypotensive dose of nimodipine (1 mg/kg/day) for a duration of five days. The wet/dry method was employed to identify cerebral edema, and the Evans blue dye extravasation technique was used to assess the permeability of the BBB. Furthermore, immunofluorescence staining was utilized to assess the protein expression levels of matrix metalloproteinase-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1). The study also examined mitochondrial function by evaluating mitochondrial swelling, succinate dehydrogenase (SDH) activity, the collapse of mitochondrial membrane potential (MMP), and the generation of reactive oxygen species (ROS). Post-stroke administration of nimodipine led to a significant decrease in cerebral edema and maintained the integrity of the BBB. The protective effects observed were associated with a reduction in cell apoptosis as well as decreased expression of MMP-9 and ICAM-1. Furthermore, nimodipine was observed to reduce mitochondrial swelling and ROS levels while simultaneously restoring MMP and SDH activity. These results suggest that nimodipine may reduce cerebral edema and BBB breakdown caused by ischemia/reperfusion. This effect is potentially mediated through the reduction of MMP-9 and ICAM-1 levels and the enhancement of mitochondrial function.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
فهرسة مساهمة: Keywords: Brain edema; ICAM-1; MMP-9; Mitochondrial dysfunction; Nimodipine; Stroke
المشرفين على المادة: 57WA9QZ5WH (Nimodipine)
EC 3.4.24.35 (Matrix Metalloproteinase 9)
0 (Calcium Channel Blockers)
0 (Reactive Oxygen Species)
126547-89-5 (Intercellular Adhesion Molecule-1)
EC 1.3.99.1 (Succinate Dehydrogenase)
EC 3.4.24.35 (Mmp9 protein, rat)
تواريخ الأحداث: Date Created: 20240701 Date Completed: 20240720 Latest Revision: 20240720
رمز التحديث: 20240721
DOI: 10.1016/j.neuropharm.2024.110054
PMID: 38950691
قاعدة البيانات: MEDLINE
الوصف
تدمد:1873-7064
DOI:10.1016/j.neuropharm.2024.110054