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Int. J. Mol. Sci. 2018, 19(1), 162; https://doi.org/10.3390/ijms19010162

Effects of Fluoxetine on Hippocampal Neurogenesis and Neuroprotection in the Model of Global Cerebral Ischemia in Rats

1
Laboratory of Neurobiology, Research Institute of Biology and Biophysics, Tomsk State University, 36, Lenina Ave., Tomsk 634050, Russia
2
E.D. Goldberg Institute of Pharmacology and Regenerative Medicine, 3, Lenina Ave., Tomsk 634028, Russia
3
Department of Radiology, University of Washington, Seattle, WA 98195, USA
*
Author to whom correspondence should be addressed.
Received: 1 November 2017 / Revised: 27 December 2017 / Accepted: 2 January 2018 / Published: 5 January 2018
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Abstract

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. View Full-Text
Keywords: global brain ischemia; neurogenesis; fluoxetine; hippocampus; dentate gyrus; inflammation; CA1; antidepressants; neural stem cells; rats global brain ischemia; neurogenesis; fluoxetine; hippocampus; dentate gyrus; inflammation; CA1; antidepressants; neural stem cells; rats
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Khodanovich, M.; Kisel, A.; Kudabaeva, M.; Chernysheva, G.; Smolyakova, V.; Krutenkova, E.; Wasserlauf, I.; Plotnikov, M.; Yarnykh, V. Effects of Fluoxetine on Hippocampal Neurogenesis and Neuroprotection in the Model of Global Cerebral Ischemia in Rats. Int. J. Mol. Sci. 2018, 19, 162.

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