Fluoxetine enhanced neurogenesis is not translated to functional outcome in stroke rats

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.