Prevent complications

Poststroke Depression

We seek to make further inroads into understanding the complex interaction between depression and brain ischemia at a mechanistic level.
More information/project description

Research Group Endres
Research Group Gertz

Project Description

The pathomechanisms underlying the development of PSD remain poorly understood, not least because of a continued lack of suitable animal models. In ongoing experiments, we have been able to demonstrate in a well characterized stroke model in mice that animals develop a depression-like phenotype characterized by anhedonia, increased anxiety, and despair following left, but not right, transient middle cerebral artery occlusion (MCAO). This experimental finding addresses an important aspect of a long-lasting controversy in the clinical literature on whether certain lesion sites predispose to PSD.

Moreover, the affective syndrome after stroke was associated with structural and functional alterations of the mesolimbic reward system. Specifically, transient MCAO resulted in delayed exofocal neurodegeneration of dopaminergic neurons in ipsilateral midbrain, which was accompanied by reduced dopamine concentrations along with increased brain-derived neurotrophic factor (BDNF) protein levels in ischemic striatum. Our findings therefore provide a biological mechanism for the development of post-stroke depression.

Chronic daily treatment with the selective serotonin reuptake inhibitor citalopram, which was only initiated 7 days post event, not only completely reversed the behavioral phenotype in MCAO mice. Surprisingly, citalopram treatment also largely prevented degeneration of dopaminergic midbrain neurons, attenuated the extent of striatal atrophy and prevented the steep decrease in striatal dopamine levels at four months. Reduction of secondary neuronal injury may provide a novel target to afford recovery after brain ischemia. Importantly, it may also underlie the clinical benefits of antidepressant therapy after stroke.

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