Neuroprotective effects of Daphnetin on hippocampal neurons and blood-brain barrier integrity in a mouse model of cerebral ischemia
The purpose of this research was to assess the impact of different doses of Daphnetin (DAP, a natural compound derived from coumarin) on hippocampus neuronal injury, neurobehavioral function, blood-brain barrier (BBB) integrity, expression of claudin-5, brain-derived neurotrophic factor (BDNF), supe...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-11-01
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| Series: | Brain Research Bulletin |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0361923024002375 |
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| author | Maysam Havasi Mehr Shahein Momenabadi Ali Vakili Abbas Pakdel Abbas Ali Vafaei Abedin Vakili |
| author_facet | Maysam Havasi Mehr Shahein Momenabadi Ali Vakili Abbas Pakdel Abbas Ali Vafaei Abedin Vakili |
| author_sort | Maysam Havasi Mehr |
| collection | DOAJ |
| description | The purpose of this research was to assess the impact of different doses of Daphnetin (DAP, a natural compound derived from coumarin) on hippocampus neuronal injury, neurobehavioral function, blood-brain barrier (BBB) integrity, expression of claudin-5, brain-derived neurotrophic factor (BDNF), superoxide dismutase (SOD), and inflammatory markers in a mouse model of cerebral ischemia. Cerebral ischemia was induced in mice through 30 minutes of bilateral common carotid occlusion (BCCAO), followed by 48 hours of reperfusion. The viability of hippocampal neurons was assessed using Cresyl violet staining and BBB function was determined by measuring Evans blue (E.B) dye leakage. Spatial memory was tested using the Radial Arm Water Maze (RAWM) task. Claudin-5 and BDNF were measured by immunofluorescence, while SOD, interleukin-1 beta (IL-1β), and nuclear factor-κB (NF-κB) expression were determined through western blotting. Administering DAP significantly increased neuron survival in the hippocampus CA1, CA3, and dentate gyrus (DG) regions and improved spatial memory dose-dependently (P<0.0001). Treatment with DAP (40 mg/kg IP) significantly reduced E.B leakage and brain water content (P<0.001). Furthermore, it increased the claudin-5, BDNF, and SOD levels and diminished NF-κB and IL-1β expression (P<0.0001). The research found that DAP protected neurons in the CA1, CA3, and DG areas of the hippocampus, enhanced behavioral functions, and preserved BBB integrity in a cerebral ischemia model. This positive impact is achieved by increasing the expression of claudin-5, BDNF, and SOD and diminishing neuroinflammation. Further research is required to clarify the mechanisms and possible clinical uses. |
| format | Article |
| id | doaj-art-209ae87b56284de9becd00ece9298bf9 |
| institution | OA Journals |
| issn | 1873-2747 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Research Bulletin |
| spelling | doaj-art-209ae87b56284de9becd00ece9298bf92025-08-20T02:13:20ZengElsevierBrain Research Bulletin1873-27472024-11-0121811110310.1016/j.brainresbull.2024.111103Neuroprotective effects of Daphnetin on hippocampal neurons and blood-brain barrier integrity in a mouse model of cerebral ischemiaMaysam Havasi Mehr0Shahein Momenabadi1Ali Vakili2Abbas Pakdel3Abbas Ali Vafaei4Abedin Vakili5Research Center of Physiology, Semnan University of Medical Sciences, IranResearch Center of Physiology, Semnan University of Medical Sciences, IranDepartment of Physiology, Semnan University of Medical Sciences, IranDepartment of Biochemistry, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, IranResearch Center of Physiology, Semnan University of Medical Sciences, IranResearch Center of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran; Corresponding author.The purpose of this research was to assess the impact of different doses of Daphnetin (DAP, a natural compound derived from coumarin) on hippocampus neuronal injury, neurobehavioral function, blood-brain barrier (BBB) integrity, expression of claudin-5, brain-derived neurotrophic factor (BDNF), superoxide dismutase (SOD), and inflammatory markers in a mouse model of cerebral ischemia. Cerebral ischemia was induced in mice through 30 minutes of bilateral common carotid occlusion (BCCAO), followed by 48 hours of reperfusion. The viability of hippocampal neurons was assessed using Cresyl violet staining and BBB function was determined by measuring Evans blue (E.B) dye leakage. Spatial memory was tested using the Radial Arm Water Maze (RAWM) task. Claudin-5 and BDNF were measured by immunofluorescence, while SOD, interleukin-1 beta (IL-1β), and nuclear factor-κB (NF-κB) expression were determined through western blotting. Administering DAP significantly increased neuron survival in the hippocampus CA1, CA3, and dentate gyrus (DG) regions and improved spatial memory dose-dependently (P<0.0001). Treatment with DAP (40 mg/kg IP) significantly reduced E.B leakage and brain water content (P<0.001). Furthermore, it increased the claudin-5, BDNF, and SOD levels and diminished NF-κB and IL-1β expression (P<0.0001). The research found that DAP protected neurons in the CA1, CA3, and DG areas of the hippocampus, enhanced behavioral functions, and preserved BBB integrity in a cerebral ischemia model. This positive impact is achieved by increasing the expression of claudin-5, BDNF, and SOD and diminishing neuroinflammation. Further research is required to clarify the mechanisms and possible clinical uses.http://www.sciencedirect.com/science/article/pii/S0361923024002375DaphnetinCerebral ischemiaHippocampusBBBSpatial memoryClaudin-5 |
| spellingShingle | Maysam Havasi Mehr Shahein Momenabadi Ali Vakili Abbas Pakdel Abbas Ali Vafaei Abedin Vakili Neuroprotective effects of Daphnetin on hippocampal neurons and blood-brain barrier integrity in a mouse model of cerebral ischemia Brain Research Bulletin Daphnetin Cerebral ischemia Hippocampus BBB Spatial memory Claudin-5 |
| title | Neuroprotective effects of Daphnetin on hippocampal neurons and blood-brain barrier integrity in a mouse model of cerebral ischemia |
| title_full | Neuroprotective effects of Daphnetin on hippocampal neurons and blood-brain barrier integrity in a mouse model of cerebral ischemia |
| title_fullStr | Neuroprotective effects of Daphnetin on hippocampal neurons and blood-brain barrier integrity in a mouse model of cerebral ischemia |
| title_full_unstemmed | Neuroprotective effects of Daphnetin on hippocampal neurons and blood-brain barrier integrity in a mouse model of cerebral ischemia |
| title_short | Neuroprotective effects of Daphnetin on hippocampal neurons and blood-brain barrier integrity in a mouse model of cerebral ischemia |
| title_sort | neuroprotective effects of daphnetin on hippocampal neurons and blood brain barrier integrity in a mouse model of cerebral ischemia |
| topic | Daphnetin Cerebral ischemia Hippocampus BBB Spatial memory Claudin-5 |
| url | http://www.sciencedirect.com/science/article/pii/S0361923024002375 |
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