Department of Neurosurgery, University of Schleswig-Holstein Medical Center, Kiel D43 TW001035, Germany.
Glia. 2010 Jun;58(8):916-31. doi: 10.1002/glia.20974.
Inflammatory cascades induced by spinal cord injuries (SCI) are localized in the white matter, a recognized neural stem- and progenitor-cell (NSPC) niche of the adult spinal cord. Chemokines, as integrators of these processes, might also be important determinants of this NSPC niche. CCL3/CCR1, CCL2/CCR2, and SDF-1alpha/CXCR4 were analyzed in the ventrolateral white matter after force defined thoracic SCI: Immunoreactivity (IR) density levels were measured 2 d, 7 d, 14 d, and 42 d on cervical (C 5), thoracic (T 5), and lumbar (L 5) levels. On day post operation (DPO) 42, chemokine inductions were further evaluated by real-time RT-PCR and Western blot analyses. Cellular phenotypes were confirmed by double labeling with markers for major cell types and NSPCs (nestin, Musashi-1, NG2, 3CB2, BLBP). Mitotic profiles were investigated in parallel by BrdU labeling. After lesion, chemokines were induced in the ventrolateral white matter on IR-, mRNA-, and protein-level. IR was generally more pronounced after severe lesions, with soaring increases of CCL2/CCR2 and continuous elevations of CCL3/CCR1. SDF-1alpha and CXCR4 IR induction was focused on thoracic levels. Chemokines/-receptors were co-expressed with astroglial, oligodendroglial markers, nestin, 3CB2 and BLBP by cells morphologically resembling radial glia on DPO 7 to DPO 42, and NG2 or Musashi-1 on DPO 2 and 7. In the white matter BrdU positive cells were significantly elevated after lesion compared with sham controls on all investigated time points peaking in the early time course on thoracic level: Here, chemokines were co-expressed by subsets of BrdU-labeled cells. These findings suggest an important role of chemokines/-receptors in the subpial white matter NSPC niche after SCI.
脊髓损伤 (SCI) 引起的炎症级联反应局限于白质，白质是成人脊髓中公认的神经干细胞和祖细胞 (NSPC) 龛位。趋化因子作为这些过程的整合者，也可能是 NSPC 龛位的重要决定因素。在明确的胸 SCI 后，对腹外侧白质中的 CCL3/CCR1、CCL2/CCR2 和 SDF-1alpha/CXCR4 进行了分析：在颈椎 (C5)、胸椎 (T5) 和腰椎 (L5) 水平上，在 2d、7d、14d 和 42d 测量了免疫反应 (IR) 密度水平。在手术后第 42 天 (DPO)，通过实时 RT-PCR 和 Western blot 分析进一步评估趋化因子的诱导。通过与主要细胞类型和 NSPC（巢蛋白、Musashi-1、NG2、3CB2、BLBP）的标志物进行双重标记来确认细胞表型。通过 BrdU 标记同时研究有丝分裂谱。损伤后，趋化因子在腹外侧白质中诱导出 IR、mRNA 和蛋白质水平。IR 在后严重病变中更为明显，CCL2/CCR2 急剧增加，CCL3/CCR1 持续升高。SDF-1alpha 和 CXCR4 IR 诱导集中在胸椎水平。在 DPO 7 至 DPO 42 期间，形态上类似于放射状胶质细胞的细胞共同表达趋化因子/-受体、星形胶质细胞、少突胶质细胞标志物、巢蛋白、3CB2 和 BLBP，而在 DPO 2 和 7 期间，NG2 或 Musashi-1 共同表达趋化因子/-受体。在白质中，与假手术对照组相比，损伤后 BrdU 阳性细胞在所有研究时间点均显著升高，在胸椎水平的早期时间过程中达到峰值：在此，趋化因子被 BrdU 标记细胞的亚群共同表达。这些发现表明趋化因子/-受体在 SCI 后脊髓 subpial 白质 NSPC 龛位中具有重要作用。
