Lumbar Myeloid Cell Trafficking into Locomotor Networks after Thoracic Spinal Cord Injury.
Lumbar Myeloid Cell Trafficking into Locomotor Networks after Thoracic Spinal Cord Injury.
复制标题
胸部脊髓损伤后，腰部髓样细胞运输到运动网络中。
DOI：
10.1016/j.expneurol.2016.05.019
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发表时间：
2016-08
影响因子：
5.3
通讯作者：
Basso DM
中科院分区：
文献类型：
--
作者：
Hansen CN;Norden DM;Faw TD;Deibert R;Wohleb ES;Sheridan JF;Godbout JP;Basso DM
脊髓损伤 (SCI) 会促进神经轴炎症，危及可塑性、内在修复和恢复。虽然损伤部位的炎症已得到证实，但远程脊柱网络内的炎症却知之甚少。这些区域中骨髓源性免疫（髓样）细胞的存在可能会进一步阻碍功能恢复。此前，胸部 SCI 后腰椎增大处出现高水平的明胶酶、基质金属蛋白酶 9 (MMP-9)，并阻碍了活动依赖性恢复。由于 SCI 诱导的 MMP-9 可能会增加血管通透性，因此骨髓细胞浸润可能会导致运动网络中的炎症毒性。因此，我们检查了胸部 SCI 后腰脊髓的神经血管反应性和骨髓细胞浸润。我们展示了髓样细胞在腰椎而非颈部区域的区域特异性募集的证据。损伤后 24 小时和 7 天，发生髓样浸润，同时腰椎血管系统周围的趋化剂 (CCL2) 和细胞粘附分子 (ICAM-1) 增加。 SCI 后 24 小时，骨髓 GFP 嵌合小鼠建立了骨髓源性骨髓细胞向腰部灰质的牢固浸润。当血脊髓屏障完整时，就会发生这种细胞浸润，表明细胞会通过内皮细胞进行积极的募集。损伤后 7 天，骨髓细胞仍以分支巨噬细胞的形式持续存在，同时抑制性 GAD67 标记也增加。重要的是，巨噬细胞浸润需要 MMP-9。
Spinal cord injury (SCI) promotes inflammation along the neuroaxis that jeopardizes plasticity, intrinsic repair and recovery. While inflammation at the injury site is well-established, less is known within remote spinal networks. The presence of bone marrow-derived immune (myeloid) cells in these areas may further impede functional recovery. Previously, high levels of the gelatinase, matrix metalloproteinase-9 (MMP-9) occurred within the lumbar enlargement after thoracic SCI and impeded activity-dependent recovery. Since SCI-induced MMP-9 potentially increases vascular permeability, myeloid cell infiltration may drive inflammatory toxicity in locomotor networks. Therefore, we examined neurovascular reactivity and myeloid cell infiltration in the lumbar cord after thoracic SCI. We show evidence of region-specific recruitment of myeloid cells into the lumbar but not cervical region. Myeloid infiltration occurred with concomitant increases in chemoattractants (CCL2) and cell adhesion molecules (ICAM-1) around lumbar vasculature 24 hours and 7 days post injury. Bone marrow GFP chimeric mice established robust infiltration of bone marrow-derived myeloid cells into the lumbar gray matter 24 hours after SCI. This cell infiltration occurred when the blood-spinal cord barrier was intact, suggesting active recruitment across the endothelium. Myeloid cells persisted as ramified macrophages at 7 days post injury in parallel with increased inhibitory GAD67 labeling. Importantly, macrophage infiltration required MMP-9.