Interdisciplinary stroke research

V) Post stroke depression

VI) Stress and Behavior

VII) Telemedicine

VIII) Clinical trials - the Berlin Cream&Sugar study

V) Post stroke depression
Post-stroke depression (PSD) is considered as the most frequent and important neuropsychiatric consequence of stroke, since approximately one-third of stroke survivors experience major depression. Moreover this condition can have an adverse effect on cognitive function, functional recovery and survival.

While an integrated bio-psycho-social model including both biological and psychosocial aspects of post stroke depression seems warranted, a number of studies clearly suggest that biological mechanisms play a major role in the development of post stroke depression.

• Stroke patients show a higher rate of depression compared to orthopedic patients with disabilities of comparable severity.
• Several studies proposed an association with specific lesions (left anterior and basal ganglia lesions and lesions close to frontal pole) and occurrence of post stroke depression.
• Some studies reported an association between post-stroke mania and right orbital frontal, basotemporal, basal ganglia lesions.
• It has been shown that patients with anosognosia who are unaware of their disability still develop post stroke depression.

Despite this evidence, the association of post-stroke depression to specific brain lesions is still vague and needs replication from various independent groups. Furthermore the cause of post stroke depression at a functional level is not clear.

Our approach, departing from observations in our animal model of stroke (mice show "depressive-like-behavior" after stroke which can be reversed by antidepressant treatment) is to study delayed functional, biochemical and structural changes, due to a specific ischemic lesion and replicate these findings in a group of selected stroke patients.

It might well be that these secondary changes, such as exofocal delayed degeneration of monaminergic nuclei and consecutive changes in monoamine levels of the neuronal circuits of the basal ganglia and mesolimbic pathway are determining contributors to the development of post-stroke psychiatric sequelae.

By therapeutic intervention of the secondary damage evolvement, thus also the correlate of neuro-psychiatric disease, such as PSD could be prevented. To advance to this immediate clinical implication, currently pre-clinical findings are translated into clinical studies to assess the role of the observed secondary brain changes in human.

VI) Stress and Behavior
Chronic stress and Stroke outcome and susceptibility
Bodily stress response is crucial in managing allostatic mechanisms, however, chronic activation of this system creates "allostatic load" which may in turn lead to disease. The link between cardiovascular disease and stress is well established. Epidemiologic studies indicate that classical vascular risk factors are exacerbated by stress, however the exact mechanisms by which stress may increase stroke incidence is far from being understood. By using a 28 day chronic stress paradigm we examine whether chronic stress induces endothelial dysfunction and increases stroke susceptibility. Our findings so far indicate a deleterious effect of chronic stress on the endothelium in association/relation with hypertenstion which may increase stroke susceptibility.

Post Stroke behavioral testing
For decades, histological assessments were used as the only end-point in stroke research, typically using lesion size determination to evaluate the potential therapeutic effectiveness of an agent in in-vivo stroke models. Failures in clinical trials has triggered a growing awareness in the science community that a throughout re-examination of the models and techniques used in stroke research is not only necessary but inevitable. According to this new approach, one of the keys to overcome the so-called translational road block is to use behavior testing to assess functional outcome as a relevant end-point. In line with this concept we have established a wide range of behavior tests which are suitable for in-depth behavioral analysis of post stroke disturbances observed in mice models of stroke. Seven different sensory-motor tests ranging from Pole test to Corner test, anxiety tests such as plus maze and light dark box, tests for depression like behavior, memory and activity tests are successfully used in our research.

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