Effects of Dopamine Signaling on Recovery and Inflammation after Ischemic Stroke

Sammanfattning: Ischemic stroke, resulting from occlusion of a brain artery is the most common type of stroke with a prevalence of 15 million people and the leading cause of long-term disability worldwide. Importantly, partial spontaneous recovery of lost neurological functions occurs mainly during the first months after stroke onset, albeit to a limited extent. Recovery has been attributed to mechanisms of compensation but also by activation of endogenous repair processes. The area surrounding the infarct has been extensively studied and revealed functional and structural changes, however, the exact mechanisms underlying functional recovery have not been elucidated. The focus of the present study has been to investigate if levodopa/benserazide treatment, a common medication used as symptomatic treatment in Parkinson’s disease, affects processes enhancing recovery after stroke. Importantly levodopa/benserazide treatment also enhanced motor recovery and motor learning in preliminary stroke trials. In a reverse translational approach we have demonstrated an improved functional recovery by levodopa/benserazide treatment in a rat stroke model. We identified astrocytes and immune cells to respond to the treatment and to be involved in recovery enhancing effects. Among the processes affected by dopamine signaling were increased levels of the astrocyte derived neurotrophic factor, glial cell line-derived neurotrophic factor. In addition, we also demonstrated for the first time that dopamine signaling modulates inflammatory processes in the postischemic brain and periphery involving T-cells. Overall this investigation presents novel data regarding the role of dopamine signaling in the postischemic brain of relevance for recovery after stroke.