Effects of Fluoxetine on Hippocampal Neurogenesis and Neuroprotection in the Model of Global Cerebral Ischemia in Rats
A selective serotonin reuptake inhibitor, fluoxetine, has recently attracted a significant interest as a neuroprotective therapeutic agent. There is substantial evidence of improved neurogenesis under fluoxetine treatment of brain ischemia in animal stroke models. We studied long-term effects of flu...
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| Format: | Article |
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MDPI AG
2018-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | http://www.mdpi.com/1422-0067/19/1/162 |
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| author | Marina Khodanovich Alena Kisel Marina Kudabaeva Galina Chernysheva Vera Smolyakova Elena Krutenkova Irina Wasserlauf Mark Plotnikov Vasily Yarnykh |
| author_facet | Marina Khodanovich Alena Kisel Marina Kudabaeva Galina Chernysheva Vera Smolyakova Elena Krutenkova Irina Wasserlauf Mark Plotnikov Vasily Yarnykh |
| author_sort | Marina Khodanovich |
| collection | DOAJ |
| description | A selective serotonin reuptake inhibitor, fluoxetine, has recently attracted a significant interest as a neuroprotective therapeutic agent. There is substantial evidence of improved neurogenesis under fluoxetine treatment of brain ischemia in animal stroke models. We studied long-term effects of fluoxetine treatment on hippocampal neurogenesis, neuronal loss, inflammation, and functional recovery in a new model of global cerebral ischemia (GCI). Brain ischemia was induced in adult Wistar male rats by transient occlusion of three main vessels originating from the aortic arch and providing brain blood supply. Fluoxetine was injected intraperitoneally in a dose of 20 mg/kg for 10 days after surgery. To evaluate hippocampal neurogenesis at time points 10 and 30 days, 5-Bromo-2′-deoxyuridine was injected at days 8–10 after GCI. According to our results, 10-day fluoxetine injections decreased neuronal loss and inflammation, improved survival and functional recovery of animals, enhanced neurogenesis, and prevented an early pathological increase in neural stem cell recruitment in the subgranular zone (SGZ) of the hippocampus without reducing the number of mature neurons at day 30 after GCI. In summary, this study suggests that fluoxetine may provide a promising therapy in cerebral ischemia due to its neuroprotective, anti-inflammatory, and neurorestorative effect. |
| first_indexed | 2024-04-12T17:10:40Z |
| format | Article |
| id | doaj.art-ead3c56cf1c6430d8a86185720064324 |
| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-12T17:10:40Z |
| publishDate | 2018-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ead3c56cf1c6430d8a861857200643242022-12-22T03:23:48ZengMDPI AGInternational Journal of Molecular Sciences1422-00672018-01-0119116210.3390/ijms19010162ijms19010162Effects of Fluoxetine on Hippocampal Neurogenesis and Neuroprotection in the Model of Global Cerebral Ischemia in RatsMarina Khodanovich0Alena Kisel1Marina Kudabaeva2Galina Chernysheva3Vera Smolyakova4Elena Krutenkova5Irina Wasserlauf6Mark Plotnikov7Vasily Yarnykh8Laboratory of Neurobiology, Research Institute of Biology and Biophysics, Tomsk State University, 36, Lenina Ave., Tomsk 634050, RussiaLaboratory of Neurobiology, Research Institute of Biology and Biophysics, Tomsk State University, 36, Lenina Ave., Tomsk 634050, RussiaLaboratory of Neurobiology, Research Institute of Biology and Biophysics, Tomsk State University, 36, Lenina Ave., Tomsk 634050, RussiaE.D. Goldberg Institute of Pharmacology and Regenerative Medicine, 3, Lenina Ave., Tomsk 634028, RussiaE.D. Goldberg Institute of Pharmacology and Regenerative Medicine, 3, Lenina Ave., Tomsk 634028, RussiaLaboratory of Neurobiology, Research Institute of Biology and Biophysics, Tomsk State University, 36, Lenina Ave., Tomsk 634050, RussiaLaboratory of Neurobiology, Research Institute of Biology and Biophysics, Tomsk State University, 36, Lenina Ave., Tomsk 634050, RussiaE.D. Goldberg Institute of Pharmacology and Regenerative Medicine, 3, Lenina Ave., Tomsk 634028, RussiaLaboratory of Neurobiology, Research Institute of Biology and Biophysics, Tomsk State University, 36, Lenina Ave., Tomsk 634050, RussiaA selective serotonin reuptake inhibitor, fluoxetine, has recently attracted a significant interest as a neuroprotective therapeutic agent. There is substantial evidence of improved neurogenesis under fluoxetine treatment of brain ischemia in animal stroke models. We studied long-term effects of fluoxetine treatment on hippocampal neurogenesis, neuronal loss, inflammation, and functional recovery in a new model of global cerebral ischemia (GCI). Brain ischemia was induced in adult Wistar male rats by transient occlusion of three main vessels originating from the aortic arch and providing brain blood supply. Fluoxetine was injected intraperitoneally in a dose of 20 mg/kg for 10 days after surgery. To evaluate hippocampal neurogenesis at time points 10 and 30 days, 5-Bromo-2′-deoxyuridine was injected at days 8–10 after GCI. According to our results, 10-day fluoxetine injections decreased neuronal loss and inflammation, improved survival and functional recovery of animals, enhanced neurogenesis, and prevented an early pathological increase in neural stem cell recruitment in the subgranular zone (SGZ) of the hippocampus without reducing the number of mature neurons at day 30 after GCI. In summary, this study suggests that fluoxetine may provide a promising therapy in cerebral ischemia due to its neuroprotective, anti-inflammatory, and neurorestorative effect.http://www.mdpi.com/1422-0067/19/1/162global brain ischemianeurogenesisfluoxetinehippocampusdentate gyrusinflammationCA1antidepressantsneural stem cellsrats |
| spellingShingle | Marina Khodanovich Alena Kisel Marina Kudabaeva Galina Chernysheva Vera Smolyakova Elena Krutenkova Irina Wasserlauf Mark Plotnikov Vasily Yarnykh Effects of Fluoxetine on Hippocampal Neurogenesis and Neuroprotection in the Model of Global Cerebral Ischemia in Rats International Journal of Molecular Sciences global brain ischemia neurogenesis fluoxetine hippocampus dentate gyrus inflammation CA1 antidepressants neural stem cells rats |
| title | Effects of Fluoxetine on Hippocampal Neurogenesis and Neuroprotection in the Model of Global Cerebral Ischemia in Rats |
| title_full | Effects of Fluoxetine on Hippocampal Neurogenesis and Neuroprotection in the Model of Global Cerebral Ischemia in Rats |
| title_fullStr | Effects of Fluoxetine on Hippocampal Neurogenesis and Neuroprotection in the Model of Global Cerebral Ischemia in Rats |
| title_full_unstemmed | Effects of Fluoxetine on Hippocampal Neurogenesis and Neuroprotection in the Model of Global Cerebral Ischemia in Rats |
| title_short | Effects of Fluoxetine on Hippocampal Neurogenesis and Neuroprotection in the Model of Global Cerebral Ischemia in Rats |
| title_sort | effects of fluoxetine on hippocampal neurogenesis and neuroprotection in the model of global cerebral ischemia in rats |
| topic | global brain ischemia neurogenesis fluoxetine hippocampus dentate gyrus inflammation CA1 antidepressants neural stem cells rats |
| url | http://www.mdpi.com/1422-0067/19/1/162 |
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