Recent clinical trials have demonstrated that treatment with
selective serotonin reuptake inhibitors after
stroke enhances motor functional recovery; however, the underlying mechanisms remain to be further elucidated. We hypothesized that daily administration of the clinical
drug citalopram would produce these functional benefits via enhancing neurovascular repair in the ischemic peri-
infarct region. To test this hypothesis, focal
ischemic stroke was induced in male C57/B6 mice by permanent
ligation of distal branches of the middle cerebral artery to the barrel cortex and 7-min occlusion of the bilateral common carotid arteries.
Citalopram (10mg/kg, i.p.) was injected 24h after
stroke and daily thereafter. To label proliferating cells, bromo-
deoxyuridine was injected daily beginning 3 days after
stroke. Immunohistochemical and functional assays were performed to elucidate
citalopram-mediated cellular and sensorimotor changes after
stroke.
Citalopram treatment had no significant effect on
infarct formation or
edema 3 days after
stroke; however,
citalopram-treated mice had better functional recovery than saline-treated controls 3 and 14 days after
stroke in the adhesive removal test. Increased expression of
brain-derived neurotrophic factor was detected in the peri-
infarct region 7 days after
stroke in
citalopram-treated animals. The number of proliferating neural progenitor cells and the distance of neuroblast migration from the sub-ventricular zone toward the ischemic cortex were significantly greater in
citalopram-treated mice at 7 days after
stroke. Immunohistochemical staining and co-localization analysis showed that
citalopram-treated animals generated more new neurons and microvessels in the peri-
infarct region 21 and 28 days after
stroke. Taken together, these results suggest that
citalopram promotes post-
stroke sensorimotor recovery likely via enhancing neurogenesis, neural cell migration and the microvessel support in the peri-
infarct region of the ischemic brain.