National Trauma Research Institute, Alfred Hospital, Melbourne, Victoria, Australia.
J Cereb Blood Flow Metab. 2010 Apr;30(4):769-82. doi: 10.1038/jcbfm.2009.262. Epub 2009 Dec 23.
Cerebral inflammation involves molecular cascades contributing to progressive damage after traumatic brain injury (TBI). The chemokine CC ligand-2 (CCL2) (formerly monocyte chemoattractant protein-1, MCP-1) is implicated in macrophage recruitment into damaged parenchyma after TBI. This study analyzed the presence of CCL2 in human TBI, and further investigated the role of CCL2 in physiological and cellular mechanisms of secondary brain damage after TBI. Sustained elevation of CCL2 was detected in the cerebrospinal fluid (CSF) of severe TBI patients for 10 days after trauma, and in cortical homogenates of C57Bl/6 mice, peaking at 4 to 12 h after closed head injury (CHI). Neurological outcome, lesion volume, macrophage/microglia infiltration, astrogliosis, and the cerebral cytokine network were thus examined in CCL2-deficient (-/-) mice subjected to CHI. We found that CCL2-/- mice showed altered production of multiple cytokines acutely (2 to 24 h); however, this did not affect lesion size or cell death within the first week after CHI. In contrast, by 2 and 4 weeks, a delayed reduction in lesion volume, macrophage accumulation, and astrogliosis were observed in the injured cortex and ipsilateral thalamus of CCL2-/- mice, corresponding to improved functional recovery as compared with wild-type mice after CHI. Our findings confirm the significant role of CCL2 in mediating post-traumatic secondary brain damage.
脑炎症涉及分子级联反应，这些反应导致创伤性脑损伤（TBI）后进行性损伤。趋化因子 CC 配体-2（CCL2）（以前称为单核细胞趋化蛋白-1，MCP-1）与 TBI 后巨噬细胞募集到受损实质中有关。本研究分析了 CCL2 在人类 TBI 中的存在，并进一步研究了 CCL2 在 TBI 后继发性脑损伤的生理和细胞机制中的作用。在创伤后 10 天，严重 TBI 患者的脑脊液（CSF）中检测到 CCL2 持续升高，在 C57Bl/6 小鼠的皮质匀浆中，在闭合性颅脑损伤（CHI）后 4 至 12 小时达到峰值。因此，在接受 CHI 的 CCL2 缺陷（-/-）小鼠中检查了神经功能结局、病变体积、巨噬细胞/小胶质细胞浸润、星形胶质细胞增生和大脑细胞因子网络。我们发现，CCL2-/- 小鼠在急性（2 至 24 小时）时会改变多种细胞因子的产生；然而，这并没有影响 CHI 后第一周内的病变大小或细胞死亡。相比之下，在 2 周和 4 周时，在 CCL2-/- 小鼠的受伤皮质和同侧丘脑中观察到病变体积、巨噬细胞积累和星形胶质细胞增生的延迟减少，与 CHI 后与野生型小鼠相比，功能恢复更好。我们的研究结果证实了 CCL2 在介导创伤后继发性脑损伤中的重要作用。
