title: Fluoxetine Enhances Neurogenesis in Aged Rats with Cortical Infarcts, but This is not Reflected in a Behavioral Recovery.
abstract: Age is associated with poor outcome and impaired functional recovery after stroke. Fluoxetine, which is widely used in clinical practice, can regulate hippocampal neurogenesis in young rodents. As the rate of neurogenesis is dramatically reduced during aging, we studied the effect of post-stroke fluoxetine treatment on neurogenesis in the subventricular zone (SVZ) and subgranular zone (SGZ) of dentate gyrus (DG) and whether this would be associated with any behavioral recovery after the cortical infarct in aged rats. Aged 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. Focal cortical ischemia was induced by intracranial injection of vasoconstrictive peptide, endothelin-1 (ET-1). Fluoxetine was administered in the drinking water for 3 weeks starting 1 week after ischemia at a dose of 18 mg/kg/day. Behavioral recovery was evaluated on post-stroke days 29 to 31 after which the survival rate and fate of proliferating cells in the SVZ and DG were assessed by immunohistochemistry. Apoptosis was measured with the TUNEL assay. The results indicated that chronic fluoxetine treatment after stroke enhanced the proliferation of newborn neurons in the SVZ, but not in SGZ, and it suppressed perilesional apoptosis. Fluoxetine treatment did not affect the survival or differentiation of newly generated cells in the SVZ i.e., the enhanced neurogenesis was not translated into a behavioral outcome.
authors.affiliation: Neurology, The First Hospital of China Medical University, No.155, North Nanjing Street, Heping District, Shenyang, Liaoning, 110001, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Sun
authors.affiliation: Neurology, The First Hospital of China Medical University, No.155, North Nanjing Street, Heping District, Shenyang, Liaoning, 110001, China.
authors.forename: Zhike
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Neurology, The First Hospital of China Medical University, No.155, North Nanjing Street, Heping District, Shenyang, Liaoning, 110001, 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, No.155, North Nanjing Street, Heping District, Shenyang, Liaoning, 110001, 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, No.155, North Nanjing Street, Heping District, Shenyang, Liaoning, 110001, China. cszhao@mail.cmu.edu.cn.
authors.forename: Chuansheng
authors.initials: C
authors.lastname: Zhao
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis; D020520:Brain Infarction / Q000139:chemically induced / Q000188:drug therapy*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000254:growth & development; D019332:Endothelin-1 / Q000633:toxicity; D005473:Fluoxetine / Q000494:pharmacology / Q000627:therapeutic use*; D008124:Locomotion; D008297:Male; D055495:Neurogenesis; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018687:Antidepressive Agents, Second-Generation; D019332:Endothelin-1; D018696:Neuroprotective Agents; D005473:Fluoxetine
keywords: Aging; Behavioral recovery; Cerebral ischemia; Neurogenesis; Selective serotonin reuptake inhibitors