Neuroplasticity and behavioral effects of fluoxetine after experimental stroke

Article type: Research Article

Authors: Sun, Yefei^a | Sun, Xiaoyu^b | Qu, Huiling^b | Zhao, Shanshan^c | Xiao, Ting^{d; e} | Zhao, Chuansheng^{c; *}

Affiliations: [a] Gastrointestinal Surgery, The First Hospital of China Medical University, Shenyang, China | [b] Department of Neurology, The People’s Hospital of Liaoning Province, Shenyang, China | [c] Neurology, The First Hospital of China Medical University, Shenyang, China | [d] Dermatology, The First Hospital of China Medical University, Shenyang, China | [e] Key Laboratory of Immunodermatology, Ministry of Health, Ministry of Education, Shenyang, China

Correspondence: [*] Corresponding author: Chuansheng Zhao, No.155, North Nanjing Street, Heping District, Shenyang 110001, Liaoning, PR China. Tel.: +86 24 83282510; Fax: +86 24 83282315; E-mail: cszhao@cmu.edu.cn.

Abstract: The brain can undergo self-repair and has the ability to compensate for functions lost after a stroke. The plasticity of the ischemic brain is influenced by several factors including aging and pharmacotherapy. Fluoxetine is an antidepressant which enhances serotonergic neurotransmission through selective inhibition of neuronal reuptake of serotonin. In clinical practice, fluoxetine alleviates the symptoms of post-stroke depression (PSD), helps motor recovery in stroke patients. In animal experiments, chronic administration of fluoxetine induces increased excitability of mature granule cells (GCs), enhancing axonal and dendritic reorganization, as well as promoting neurogenesis or angiogenesis in the dentate gurus (DG), but the effect of fluoxetine in the subventricular zone (SVZ) remains controversial. Meanwhile, chronic treatment with fluoxetine did not reverse age-dependent suppression of proliferation cells in the DG. Interestingly, although fluoxetine has been found to enhance neurogenesis in the DG in stroke rats, this property is not consistent with the behavioral recovery. More studies into this issue will be required to reveal how to translate enhanced neuronal plasticity into behavioral benefits. This review provides an update of the current knowledge about the neurogenesis and the fate of the newly generated cells after the use of fluoxetine, as well as its ability to promote a behavioral recovery after stroke in clinical and experimental results and attempts to define the therapeutic properties of fluoxetine in regenerative neuroscience.

Keywords: Fluoxetine, stroke, neuroplasticity, behavioral recovery

DOI: 10.3233/RNN-170725

Journal: Restorative Neurology and Neuroscience, vol. 35, no. 5, pp. 457-468, 2017