Lack of the scavenger receptor CD36 alters microglial phenotypes after neonatal stroke.
Lack of the scavenger receptor CD36 alters microglial phenotypes after neonatal stroke.
复制标题
清道夫受体 CD36 的缺乏会改变新生儿中风后的小胶质细胞表型。
DOI：
10.1111/jnc.13239
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发表时间：
2015-11
影响因子：
4.7
通讯作者：
Vexler ZS
中科院分区：
文献类型：
--
作者：
Li F;Faustino J;Woo MS;Derugin N;Vexler ZS
脑卒中时的脑发育阶段对缺血性损伤的病理生理机制（包括神经炎症反应）具有重要影响。小胶质细胞已被证明有助于急性和亚慢性损伤的成人中风模型，而在新生啮齿动物中，我们发现，小胶质细胞作为内源性神经保护剂短暂性大脑中动脉闭塞（tMCAO）后早期，限制神经炎症和损伤。在新生儿中，小胶质细胞耗竭或清道夫受体CD 36的缺乏加剧了损伤。在这项研究中，我们询问缺乏CD 36是否会影响新生儿中风后的小胶质细胞表型。使用RT-PCR，我们的特点是在出生后10天的小鼠急性tMCAO后，从受伤的区域分离的小胶质细胞的基因表达模式，并显示，几个促炎基因的表达，包括Toll样受体（TLR），在很大程度上不受影响的激活小胶质细胞在受伤的区域。使用多种生物化学测定，我们证明了CD 36的缺乏改变了急性损伤新生儿脑中小胶质细胞的几种功能：它进一步增强了趋化因子MCP-1的积累，影响了CD 11 b +/CD 45+细胞的数量，沿着其辅助受体TLR 2的蛋白表达，但不影响小胶质细胞中超氧化物的积累或损伤区域中细胞因子TNFα和IL-1β的积累。
The stage of brain development at the time of stroke has a major impact on the pathophysiological mechanisms of ischemic damage, including the neuroinflammatory response. Microglial cells have been shown to contribute to acute and sub-chronic injury in adult stroke models, whereas in neonatal rodents we showed that microglial cells serve as endogenous neuroprotectants early following transient middle cerebral artery occlusion (tMCAO), limiting neuroinflammation and injury. In the neonate, microglial depletion or lack of the scavenger receptor CD36 exacerbates injury. In this study we asked if lack of CD36 affects microglial phenotypes after neonatal stroke. Using RT-PCR we characterized the patterns of gene expression in microglia isolated from injured regions following acute tMCAO in postnatal day 10 mice and showed that expression of several pro-inflammatory genes, including Toll-like receptors (TLR), remains largely unaffected in activated microglia in injured regions. Using multiple biochemical assays we demonstrated that lack of CD36 alters several functions of microglia in acutely injured neonatal brain: it further enhances accumulation of the chemokine MCP-1, affects the number of CD11b+/CD45+ cells, along with protein expression of its co-receptor, TLR2, but does not affect accumulation of superoxide in microglia or the cytokines TNFα and IL-1β in injured regions.