Microglia‐mediated phagocytosis of apoptotic nuclei is impaired in the adult murine hippocampus after stroke
Microglia‐mediated phagocytosis of apoptotic nuclei is impaired in the adult murine hippocampus after stroke
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DOI：
10.1002/glia.24009
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发表时间：
2021-05
期刊：
影响因子：
6.2
通讯作者：
Max Rudolph;C. Schmeer;M. Günther;Florus Woitke;Carolin Kathner-Schaffert;Lina Karapetow;Julia Lindner-Julia
中科院分区：
文献类型：
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作者：
Max Rudolph;C. Schmeer;M. Günther;Florus Woitke;Carolin Kathner-Schaffert;Lina Karapetow;Julia Lindner-Julia
中风后，神经元死亡发生在梗死区域和病变部位远端的脑区，包括海马。海马体与学习和记忆过程密切相关，并不断产生新的神经元。成人神经发生失调可能与卒中后认知功能下降有关。特别是，损伤后前体细胞的增殖和新神经元的形成增加。在第一周内，许多新的前体细胞在发育过程中死亡。死亡前体是如何从海马体中清除的，以及在中风后吞噬作用发生的程度仍然不清楚。在这里，我们评估了前额叶卒中损伤对海马齿状回（DG）小胶质细胞吞噬活性的影响。在大脑中动脉闭塞或假手术后6小时，向3个月大的C57 BL/6 J小鼠注射一次增殖标记物BrdU（250 mg/kg）。通过免疫组织化学、共聚焦显微镜和3D重建评估凋亡细胞的数量和小胶质细胞的吞噬能力。我们发现中风后早期DG中凋亡细胞数量短暂但显著增加，与小胶质细胞清除受损相关。有趣的是，新产生的前体细胞的吞噬作用不受影响。我们的研究表明，前额叶卒中病变影响DG（病变核心远端区域）中凋亡细胞的吞噬作用。吞噬功能紊乱是否可能导致炎症和适应不良过程，包括中风后的认知障碍，需要进一步研究。
Following stroke, neuronal death takes place both in the infarct region and in brain areas distal to the lesion site including the hippocampus. The hippocampus is critically involved in learning and memory processes and continuously generates new neurons. Dysregulation of adult neurogenesis may be associated with cognitive decline after a stroke lesion. In particular, proliferation of precursor cells and the formation of new neurons are increased after lesion. Within the first week, many new precursor cells die during development. How dying precursors are removed from the hippocampus and to what extent phagocytosis takes place after stroke is still not clear. Here, we evaluated the effect of a prefrontal stroke lesion on the phagocytic activity of microglia in the dentate gyrus (DG) of the hippocampus. Three‐months‐old C57BL/6J mice were injected once with the proliferation marker BrdU (250 mg/kg) 6 hr after a middle cerebral artery occlusion or sham surgery. The number of apoptotic cells and the phagocytic capacity of the microglia were evaluated by means of immunohistochemistry, confocal microscopy, and 3D‐reconstructions. We found a transient but significant increase in the number of apoptotic cells in the DG early after stroke, associated with impaired removal by microglia. Interestingly, phagocytosis of newly generated precursor cells was not affected. Our study shows that a prefrontal stroke lesion affects phagocytosis of apoptotic cells in the DG, a region distal to the lesion core. Whether disturbed phagocytosis might contribute to inflammatory‐ and maladaptive processes including cognitive impairment following stroke needs to be further investigated.