Faculty of Life Sciences, University of Manchester, Manchester, UK.
J Cereb Blood Flow Metab. 2011 Apr;31(4):1036-50. doi: 10.1038/jcbfm.2010.198. Epub 2010 Nov 3.
Stroke induces a systemic response that involves rapid activation of inflammatory cascades, followed later by immunodepression. Experimental stroke-induced responses in the bone marrow, which is the primary source of circulating monocytes and granulocytes, have not been investigated previously. We show that cerebral ischaemia induced early (4 hours) release of CXCR2-positive granulocytes from the bone marrow, which was associated with rapid systemic upregulation of CXCL1 (a ligand for CXCR2) and granulocyte-colony-stimulating factor, a key cytokine involved in the mobilisation of bone marrow leukocytes. This process involves rapid activation of nuclear factor-κB and p38 mitogen-activated protein kinase in bone marrow myeloid cells. T-cell numbers in the bone marrow increased after stroke, and bone marrow cells did not show suppressed cytokine response to bacterial endotoxin stimulation in vitro. Stroke-induced laterality observed in the brain stem and in the bone marrow indicates direct involvement of the autonomic nervous system in stroke-induced cell mobilisation. We also show that systemic inflammatory changes and leukocyte responses in the bone marrow are profoundly affected by both anaesthetic and surgical stress. We conclude that stroke influences leukocyte responses in the bone marrow through multiple mechanisms and suggest that preclinical studies should take into consideration the effect of surgical manipulation in experimental models of stroke.
中风会引起全身性反应，包括炎症级联的迅速激活，随后是免疫抑制。以前没有研究过骨髓中实验性中风诱导的反应，骨髓是循环单核细胞和粒细胞的主要来源。我们发现，脑缺血会导致骨髓中 CXCR2 阳性粒细胞早期（4 小时）释放，这与 CXCL1（CXCR2 的配体）和粒细胞集落刺激因子的快速系统性上调有关，后者是涉及动员骨髓白细胞的关键细胞因子。这个过程涉及核因子-κB 和骨髓髓样细胞中 p38 丝裂原活化蛋白激酶的迅速激活。中风后骨髓中的 T 细胞数量增加，并且骨髓细胞在体外对细菌内毒素刺激没有表现出抑制细胞因子反应。在脑干和骨髓中观察到的中风诱导的偏侧性表明自主神经系统直接参与中风诱导的细胞动员。我们还表明，全身炎症变化和骨髓中的白细胞反应受到麻醉和手术应激的深刻影响。我们得出结论，中风通过多种机制影响骨髓中的白细胞反应，并建议临床前研究应考虑手术操作对中风实验模型的影响。
