Zai Laila J, Wrathall Jean R
Department of Neuroscience, Georgetown University, Washington, DC 20057, USA.
Glia. 2005 May;50(3):247-57. doi: 10.1002/glia.20176.
After spinal cord injury (SCI), about 50% of the oligodendrocytes and astrocytes in the residual white matter at the injury site are lost by 24 h. However, chronically after SCI, the density of oligodendrocytes is normal. Previous studies have shown that the adult rat spinal cord contains a pool of proliferating glial progenitors whose progeny could help restore cell density after injury. To study proliferation in response to injury, we performed SCI on adult female rats at the T8 level, using a standardized contusion model. Animals received bromodeoxyuridine (BrdU) injections during the first week after SCI, and were perfused within 2 h for acute studies, and at 6 weeks for chronic studies. The tissue was analyzed using immunohistochemical detection of BrdU and cell marker antigens. We demonstrate that cell proliferation in the residual white matter is increased at 1-7 days after SCI, peaking on day 3. Dividing cells include oligodendrocytes, astrocytes, microglia/macrophages, and a high proportion of NG2(+) glial precursors. By 6 weeks, some cells that had been labeled 2-4 days after SCI were still present. Double immunohistochemistry showed that while very few of these cells expressed NG2 or the microglia/macrophage marker OX42, about 50% expressed CC1 or glial fibrillary acidic protein (GFAP), markers of mature oligodendrocytes and astrocytes, respectively. The post-injury environment represented by residual white matter is thus permissive to the differentiation of glial precursors. Cells that are stimulated to divide during the first week after SCI develop chronically into mature phenotypes that replace macroglia lost after injury.
脊髓损伤（SCI）后，损伤部位残留白质中约50%的少突胶质细胞和星形胶质细胞在24小时内丢失。然而，在SCI慢性期，少突胶质细胞密度正常。先前的研究表明，成年大鼠脊髓中含有一群增殖性神经胶质祖细胞，其后代有助于损伤后恢复细胞密度。为了研究对损伤的增殖反应，我们使用标准化挫伤模型，在成年雌性大鼠的T8水平进行SCI。动物在SCI后的第一周接受溴脱氧尿苷（BrdU）注射，并在2小时内灌注用于急性研究，在6周时灌注用于慢性研究。使用免疫组织化学检测BrdU和细胞标志物抗原对组织进行分析。我们证明，SCI后1 - 7天，残留白质中的细胞增殖增加，在第3天达到峰值。分裂细胞包括少突胶质细胞、星形胶质细胞、小胶质细胞/巨噬细胞以及高比例的NG2(+)神经胶质前体细胞。到6周时，一些在SCI后2 - 4天被标记的细胞仍然存在。双重免疫组织化学显示，虽然这些细胞中很少有表达NG2或小胶质细胞/巨噬细胞标志物OX42，但约50%表达CC1或胶质纤维酸性蛋白（GFAP），分别是成熟少突胶质细胞和星形胶质细胞的标志物。因此，以残留白质为代表的损伤后环境允许神经胶质前体细胞分化。在SCI后第一周被刺激分裂的细胞长期发育成成熟表型，替代损伤后丢失的大胶质细胞。
