Kuric Enida, Ruscher Karsten
Laboratory for Experimental Brain Research, Division of Neurosurgery, Department of Clinical Sciences, Lund University, BMC A13, Lund, S-22184, Sweden.
J Neuroinflammation. 2014 Aug 23;11:145. doi: 10.1186/s12974-014-0145-z.
Cerebral ischemia activates both the innate and the adaptive immune response, the latter being activated within days after the stroke onset and triggered by the recognition of foreign antigens.
In this study we have investigated the phenotype of antigen presenting cells and the levels of associated major histocompatibility complex class II (MHC II) molecules in the postischemic brain after transient occlusion of the middle cerebral artery (tMCAO) followed by levodopa/benserazide treatment. Male Sprague Dawley rats were subjected to tMCAO for 105 minutes and received levodopa (20 mg/kg)/benserazide (15 mg/kg) for 5 days starting on day 2 after tMCAO. Thereafter, immune cells were isolated from the ischemic and contralateral hemisphere and analyzed by flow cytometry. Complementarily, the spatiotemporal profile of MHC II-positive (MHC II(+)) cells was studied in the ischemic brain during the first 30 days after tMCAO; protein levels of MHC II and the levels of inflammation associated cytokines were determined in the ischemic hemisphere.
We found that microglia/macrophages represent the main MHC II expressing cell in the postischemic brain one week after tMCAO. No differences in absolute cell numbers were found between levodopa/benserazide and vehicle-treated animals. In contrast, MHC II protein levels were significant downregulated in the ischemic infarct core by levodopa/benserazide treatment. This reduction was accompanied by reduced levels of IFN-γ, TNF-α and IL-4 in the ischemic hemisphere. In the contralateral hemisphere, we exclusively detected MHC II(+) cells in the corpus callosum. Interestingly, the number of cells was increased by treatment with levodopa/benserazide independent from the infarct size 14 days after tMCAO.
Results suggest that dopamine signaling is involved in the adaptive immune response after stroke and involves microglia/macrophages.
脑缺血会激活先天性免疫反应和适应性免疫反应，后者在中风发作数天内被激活，并由外来抗原的识别所触发。
在本研究中，我们调查了大脑中动脉短暂闭塞（tMCAO）后接受左旋多巴/苄丝肼治疗的缺血后脑中抗原呈递细胞的表型以及相关主要组织相容性复合体II类（MHC II）分子的水平。雄性Sprague Dawley大鼠接受105分钟的tMCAO，并在tMCAO后第2天开始接受左旋多巴（20 mg/kg）/苄丝肼（15 mg/kg）治疗5天。此后，从缺血半球和对侧半球分离免疫细胞，并通过流式细胞术进行分析。作为补充，在tMCAO后的前30天内研究了缺血脑中MHC II阳性（MHC II(+)）细胞的时空分布；测定了缺血半球中MHC II的蛋白水平以及炎症相关细胞因子的水平。
我们发现，小胶质细胞/巨噬细胞是tMCAO后一周缺血后脑中主要表达MHC II的细胞。左旋多巴/苄丝肼治疗组和溶剂处理组动物之间的绝对细胞数量没有差异。相比之下，左旋多巴/苄丝肼治疗使缺血梗死核心中的MHC II蛋白水平显著下调。这种降低伴随着缺血半球中IFN-γ、TNF-α和IL-4水平的降低。在对侧半球，我们仅在胼胝体中检测到MHC II(+)细胞。有趣的是，tMCAO后14天，左旋多巴/苄丝肼治疗使细胞数量增加，且与梗死大小无关。
结果表明，多巴胺信号传导参与中风后的适应性免疫反应，并涉及小胶质细胞/巨噬细胞。
