Hans-Berger Department of Neurology, Jena University Hospital, Jena, Germany.
Institute of Medical Statistics and Computer Science, University Hospital Jena, Friedrich Schiller University Jena, Jena, Germany.
Glia. 2021 Aug;69(8):2006-2022. doi: 10.1002/glia.24009. Epub 2021 May 4.
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.
中风后，不仅在梗塞区域，而且在远离病变部位的脑区（包括海马体）都会发生神经元死亡。海马体在学习和记忆过程中起着至关重要的作用，并不断产生新的神经元。成体神经发生的失调可能与中风后认知能力下降有关。特别是，在病变后，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。死亡前体细胞如何从海马体中清除，以及中风后吞噬作用的程度仍不清楚。在这里，我们评估了前额叶中风病变对海马体齿状回（DG）中小胶质细胞吞噬活性的影响。3 个月大的 C57BL/6J 小鼠在大脑中动脉闭塞或假手术后 6 小时一次性注射增殖标记物 BrdU（250mg/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 中凋亡细胞的数量短暂但显著增加，与小胶质细胞清除受损有关。有趣的是，新生成的前体细胞的吞噬作用不受影响。我们的研究表明，前额叶中风病变会影响 DG 中凋亡细胞的吞噬作用，而 DG 是远离病变核心的区域。吞噬作用的紊乱是否可能导致中风后炎症和适应不良过程，包括认知障碍，需要进一步研究。
