Borges Karin, McDermott Dayna, Irier Hasan, Smith Yoland, Dingledine Raymond
Department of Pharmacology, Emory University, Atlanta, GA 30322, USA.
Exp Neurol. 2006 Oct;201(2):416-27. doi: 10.1016/j.expneurol.2006.04.031. Epub 2006 Jun 21.
Astrocytes are relatively resistant to injury compared to neurons and oligodendrocytes. Here, we report transient region-specific loss of astrocytes in mice early after pilocarpine-induced status epilepticus (SE). In the dentate hilus, immunoreactivity for glial acidic fibrillary protein (GFAP) was decreased, and the number of healthy appearing GFAP- or S100beta-positive cells was significantly reduced (> or =65%) 1 and 3 days after pilocarpine-induced SE. Many remaining GFAP-positive cells were shrunken, and 1 day after SE electron microscopy revealed numerous electron-dense degenerating astrocyte processes and degenerating glial somata in the hilus. Degeneration of GFAP-expressing cells may be linked to hilar neuronal death, because we did not observe loss of astrocytes after kainate-induced SE, after which hilar neurons remained intact. Ten days after SE, hilar GFAP immunoreactivity had returned, partially from GFAP-positive cells in the hilus. Unlike control mice, many GFAP-positive hilar processes originated from cell bodies located in the subgranular zone (SGZ). To investigate whether proliferation contributes to hilar repopulation, we injected 5-bromo-2'-deoxyuridine (BrdU) 3 days after SE. Five hours later and up to 31 days after SE, many BrdU/GFAP colabeled cells were found in the hilus and the SGZ, some with hilar processes, indicating that proliferation in both areas contributes to generation of hilar astrocytes and astrocyte processes. In contrast to pilocarpine-induced SE in mice, astrocyte degeneration was not found after pilocarpine-induced SE in rats. These findings demonstrate astrocyte degeneration in the mouse dentate hilus specifically in the mouse pilocarpine epilepsy model, followed by astrogenesis leading to hilar repopulation.
与神经元和少突胶质细胞相比，星形胶质细胞对损伤具有相对较强的抵抗力。在此，我们报告了匹鲁卡品诱导的癫痫持续状态（SE）后早期小鼠星形胶质细胞出现短暂的区域特异性缺失。在齿状回门区，胶质纤维酸性蛋白（GFAP）的免疫反应性降低，在匹鲁卡品诱导的SE后1天和3天，外观健康的GFAP或S100β阳性细胞数量显著减少（≥65%）。许多剩余的GFAP阳性细胞发生皱缩，SE后1天电子显微镜显示门区有大量电子致密的变性星形胶质细胞突起和变性的胶质细胞体。表达GFAP的细胞变性可能与门区神经元死亡有关，因为在红藻氨酸诱导的SE后我们未观察到星形胶质细胞缺失，在此之后门区神经元保持完整。SE后10天，门区GFAP免疫反应性恢复，部分来自门区内的GFAP阳性细胞。与对照小鼠不同，许多GFAP阳性的门区突起起源于位于颗粒下区（SGZ）的细胞体。为了研究增殖是否有助于门区细胞重新填充，我们在SE后3天注射了5-溴-2'-脱氧尿苷（BrdU）。SE后5小时至31天，在门区和SGZ发现许多BrdU/GFAP共标记细胞，一些细胞具有门区突起，表明这两个区域的增殖都有助于门区星形胶质细胞和星形胶质细胞突起的生成。与小鼠匹鲁卡品诱导的SE不同，大鼠匹鲁卡品诱导的SE后未发现星形胶质细胞变性。这些发现表明，在小鼠齿状回门区，特别是在小鼠匹鲁卡品癫痫模型中，星形胶质细胞发生变性，随后发生星形胶质细胞生成，导致门区细胞重新填充。
