Cerebrolysin® and Environmental Enrichment, Alone or in Combination, Ameliorate Anxiety- and Depressive-Like Behaviors in a Post-Ischemic Depression Model in Mice

Abstract

ObjectivesThis study examined the beneficial effects of cerebrolysin (CBL) and enriched environment (EE), alone or in combination, on the neurobehavioral and molecular changes in the post-ischemic depression (PID) model in mice. Materials and MethodsPID was induced in male Balb/c mice (25–30 g) by combining the transient bilateral common carotid artery occlusion (bCCAO), twice for 5 min at the interval of 10 min, with spatial restraint stress (2 h/day) for 2 weeks, started 48 h following the establishment of bCCAO model. Animals in the treatment groups received CBL (2.5 ml/kg) and/or were housed in EE (2 h/day) for two weeks. Anxiety- and depressive-like behaviors and sociability were evaluated the day after the last experiment. Changes in the serum corticosterone level, the hippocampal oxidative stress status, inflammatory cytokines, brain-derived neurotrophic factor (BDNF), and phosphorylated cAMP response element-binding protein (p-CREB)/CREB ratio were also detected. ResultsPID model induced anxiety- and depressive-like behaviors and impaired social behavior. These behavioral changes were accompanied by increased serum corticosterone level, increased lipid peroxidation, decreased antioxidant enzyme activities, reduced BDNF levels and p-CREB/CREB ratio, and increased protein levels of NF-κB and Iba-1 in the hippocampus. However, treatment with CBL and/or EE reversed behavioral and molecular changes induced by PID. ConclusionOur findings imply that the model mimics many manifestations of human PID, and CBL and EE treatments, separately or in combination, are beneficial in reducing anxiety- and- depressive-like behaviors in this model.