Rice Tiffany, Larsen Jennifer, Rivest Serge, Yong V Wee
Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada.
J Neuropathol Exp Neurol. 2007 Mar;66(3):184-95. doi: 10.1097/01.jnen.0000248552.07338.7f.
The occurrence of neuroinflammation after spinal cord injury (SCI) is well established, but its function is debated, with both beneficial and detrimental consequences ascribed. A discriminate of the role of neuroinflammation may be the time period after SCI, and there is evidence to favor early neuroinflammation being undesirable, whereas the later evolving phase may have useful roles. Here, we have focused on the inflammatory response in the first 24 hours of SCI in mice. We found elevation of interleukin (IL)-1beta and other cytokines and chemokines within 15 minutes to 3 hours of injury. The early neuroinflammation in SCI is likely to be CNS-derived and involves microglia, as demonstrated by in situ hybridization for IL-1beta in microglia, by an in vitro model of SCI in which elevation of inflammatory cytokines occurs in the absence of a dynamic source of infiltrating leukocytes, and by the correlation of decreased levels of inflammatory molecules and microglia activity in IL-1beta-null mice. Nonetheless, as there are no specific immunohistochemical markers that clearly differentiate microglia from their peripheral counterparts, macrophages, the latter cannot be definitively excluded as participants in early neuroinflammation in mouse SCI. These results of an instantaneous inflammatory response validate approaches to modulate microglia/macrophage activity to improve recovery from SCI.
脊髓损伤（SCI）后神经炎症的发生已得到充分证实，但其功能仍存在争议，有人认为其既有有益影响，也有有害影响。区分神经炎症作用的一个因素可能是SCI后的时间段，有证据表明早期神经炎症是不利的，而后期演变阶段可能具有有益作用。在此，我们重点研究了小鼠SCI后最初24小时内的炎症反应。我们发现在损伤后15分钟至3小时内白细胞介素（IL）-1β及其他细胞因子和趋化因子水平升高。SCI早期的神经炎症可能源自中枢神经系统，且涉及小胶质细胞，这一点通过对小胶质细胞中IL-1β进行原位杂交、通过一种SCI体外模型（在该模型中，在没有动态浸润白细胞来源的情况下炎症细胞因子水平升高）以及通过IL-1β基因敲除小鼠中炎症分子水平降低与小胶质细胞活性之间的相关性得以证明。然而，由于没有能明确区分小胶质细胞与其外周对应物巨噬细胞的特异性免疫组化标志物，因此不能完全排除后者参与小鼠SCI早期神经炎症的可能性。这些关于即时炎症反应的结果验证了调节小胶质细胞/巨噬细胞活性以促进SCI恢复的方法。
