Urbach Anja, Brueckner Judith, Witte Otto W
Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany.
1] Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany [2] Center for Sepsis Control and Care, Jena University Hospital and Friedrich Schiller University Jena, Jena, Germany.
J Cereb Blood Flow Metab. 2015 Mar 31;35(4):576-82. doi: 10.1038/jcbfm.2014.232.
Recently, we showed that cortical spreading depolarizations (CSDs) are a potent trigger of hippocampal neurogenesis. Here, we evaluated CSD-induced cytogenesis in the entorhinal cortex (EC), which provides the major afferent input to the dentate gyrus. Cortical spreading depolarizations were induced by epidural application of 3 mol/L KCl, controls received equimolar NaCl. Cytogenesis was analyzed at different time points thereafter by means of intraperitoneal 5-bromodeoxyuridine injections (day 2, 4, or days 1 to 7) and immunohistochemistry. Recurrent CSD significantly increased numbers of newborn cells in the ipsilateral EC. The majority of these cells expressed glial markers. Microglia proliferation was maximal at day 2, whereas NG2 glia and astrocytes responded for a prolonged period of time (days 2 to 4). Newborn glia remained detectable for 6 weeks after CSD. Whereas we furthermore detected newborn cells immunopositive for doublecortin, a marker for immature neuronal cells, we found no evidence for the generation of new neurons in the EC. Our results indicate that CSD is a potent gliogenic stimulus, leading to rapid and enduring changes in the glial cellular composition of the affected brain tissue. Thus, CSD facilitates ongoing structural remodeling of the directly affected cortex that might contribute to the pathophysiology of CSD-related brain pathologies.
最近，我们发现皮层扩散性去极化（CSDs）是海马神经发生的一个有力触发因素。在此，我们评估了CSD诱导的内嗅皮层（EC）的细胞生成情况，内嗅皮层为齿状回提供主要的传入输入。通过硬膜外应用3 mol/L KCl诱导皮层扩散性去极化，对照组接受等摩尔的NaCl。此后，通过腹腔注射5-溴脱氧尿苷（第2天、第4天或第1至7天）和免疫组织化学在不同时间点分析细胞生成情况。复发性CSD显著增加了同侧EC中新生细胞的数量。这些细胞中的大多数表达胶质细胞标志物。小胶质细胞增殖在第2天达到最大值，而NG2胶质细胞和星形胶质细胞的反应持续较长时间（第2至4天）。CSD后6周仍可检测到新生胶质细胞。虽然我们还检测到了对双皮质素呈免疫阳性的新生细胞，双皮质素是未成熟神经元细胞的标志物，但我们没有发现内嗅皮层中有新神经元生成的证据。我们的结果表明，CSD是一种强大的胶质细胞生成刺激因素，导致受影响脑组织的胶质细胞组成发生快速且持久的变化。因此，CSD促进了直接受影响皮层正在进行的结构重塑，这可能有助于与CSD相关的脑部疾病的病理生理学过程。
