title: Reduction of rat brain CD8+ T-cells by levodopa/benserazide treatment after experimental stroke.
abstract: 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.
authors.affiliation: Laboratory for Experimental Brain Research, Division of Neurosurgery, Department of Clinical Sciences, Lund University, BMC A13, S-22184, Lund, Sweden.
authors.forename: Enida
authors.initials: E
authors.lastname: Kuric
authors.forename: Karsten
authors.initials: K
authors.lastname: Ruscher
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D001545:Benserazide / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects*; D054360:Chemokine CXCL1 / Q000235:genetics / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D007980:Levodopa / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000978:Antiparkinson Agents; D054360:Chemokine CXCL1; D007378:Interleukins; D018799:Intercellular Adhesion Molecule-1; D007980:Levodopa; D001545:Benserazide; D007371:Interferon-gamma
keywords: cerebral ischemia; dopamine; immunomodulation; inflammation; recovery