title: Fluoxetine enhanced neurogenesis is not translated to functional outcome in stroke rats.
abstract: Fluoxetine is widely used in clinical practice. It regulates hippocampal neurogenesis, however, the effect of fluoxetine on neurogenesis in the subventricular zone (SVZ) remains controversial. We aimed to study the effect of fluoxetine on neurogenesis in the SVZ and subgranular zone (SGZ) of dentate gyrus (DG) in relation to behavioral recovery after stroke in rats. Adult male Wistar rats were randomly assigned to four groups: sham-operated rats, sham-operated rats treated with fluoxetine, rats subjected to cerebral ischemia, and rats with ischemia treated with fluoxetine. Fluoxetine was orally administrated starting 1 week after ischemia, with a dose of 16mg/kg/day for 3 weeks. Focal cerebral ischemia was induced by intracranial injection of vasoconstrictive peptide endothelin-1(ET-1). Behavioral recovery was evaluated on post-stroke days 29-31 after which the survival rate and fate of proliferating cells in the SVZ and DG were measured by immunohistochemistry. The production of neuroblasts in both the SVZ and DG was significantly increased after stroke. Chronic post-stroke fluoxetine treatment increased the dendritic complexity of newborn dentate granule cells. However, fluoxetine treatment did not influence the survival or differentiation of newly generated cells. Neither fluoxetine treatment improved sensorimotor recovery following focal cerebral ischemia.
authors.affiliation: Neurology, The first hospital of China Medical University, Shenyang, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Sun
authors.affiliation: Interventional Neuroradiology, Beijing Tian Tan Hospital, Capital Medical University, Beijing, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Sun
authors.affiliation: Neurology, The first hospital of China Medical University, Shenyang, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Liu
authors.affiliation: Cardiology, Shengjing hospital of China Medical University, Shenyang, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Neurology, The first hospital of China Medical University, Shenyang, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Dermatology, The first hospital of China Medical University, Shenyang, China; Key Laboratory of Immunodermatology, Ministry of Health, Ministry of Education, Shenyang, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Xiao
authors.affiliation: Institute of Clinical Medicine - Neurology, University of Eastern Finland, P. O. Box 1627, 70211 Kuopio, Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Jolkkonen
authors.affiliation: Neurology, The first hospital of China Medical University, Shenyang, China. Electronic address: cszhao@mail.cmu.edu.cn.
authors.forename: Chuansheng
authors.initials: C
authors.lastname: Zhao
mesh_terms: D000818:Animals; D020520:Brain Infarction / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology; D003712:Dendrites / Q000187:drug effects / Q000473:pathology; D018891:Dentate Gyrus / Q000187:drug effects* / Q000473:pathology; D005473:Fluoxetine / Q000627:therapeutic use*; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D020547:Lateral Ventricles / Q000187:drug effects* / Q000473:pathology; D008297:Male; D055495:Neurogenesis; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D011897:Random Allocation; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
chemical_list: D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Functional recovery; Neurogenesis; Selective serotonin reuptake inhibitors; Stroke; Subventricular zone