The activation of inflammatory cascades in the ischemic hemisphere impairs mechanisms of tissue reorganization with consequences for recovery of lost neurological function. Recruitment of T-cell populations to the post-ischemic brain occurs and represents a significant part of the inflammatory response. This study was conducted to investigate if treatment with levodopa, potentially acting as an immunomodulator, affects the T-cell accumulation in the post-ischemic brain. Male Sprague–Dawley rats were subjected to transient occlusion of the middle cerebral artery (tMCAO) for 105 min followed by levodopa/benserazide treatment (20 mg/kg/15 mg/kg) for 5 days initiated on day 2 post-stroke. One week after tMCAO, T-cell populations were analysed from brains, and levels of interleukin (IL)-1β, chemokine (C-X-C motif) ligand 1, IL-4, IL-5, interferon gamma and IL-13 were analysed. After levodopa/benserazide treatment, we found a significant reduction of cytotoxic T-cells (CD3+CD8+) in the ischemic hemisphere together with reduced levels of T-cell-associated cytokine IL-5, while other T-cell populations (CD3+, CD3+CD4+, CD3+CD4+CD25+) were unchanged compared with vehicle-treated rats. Moreover, a reduced number of cells was associated with reduced levels of intercellular adhesion molecule 1, expressed in endothelial cells, in the infarct core of levodopa/benserazide-treated animals. Together, we provide the first evidence that dopamine can act as a potential immunomodulator by attenuating inflammation in the post-ischemic brain.
Treatment with levodopa initiated on day 2 and continued for 5 days after after transient occlusion of the middle cerebral artery (tMCAO) significantly reduces the number of CD3+/CD8+ T-cells and pro-inflammatory cytokines in the ischemic hemisphere. We also show that levodopa treatment decreased the levels of Intercellular Adhesion Molecule 1 (ICAM-1) in the ischemic territory.