Accumulated data have revealed that subacute poisoning of 1,2-dichloroethane (1,2-DCE), an industrial solvent used in some countries can cause encephalopathy, in which brain edema is the main pathological change. However, the underlying mechanisms are unclear. In the present study, we hypothesized that the p38 MAPK (p38) signaling pathway could be activated in 1,2-DCE-intoxicated mice, which in turn stimulates transcription factors, such as nuclear factor-κB (NF-κB) and activator protein-1 (AP-1), and then enhances the expression of proinflammatory factors, including matrix metalloproteinase-9 (MMP-9), finally leading to blood-brain barrier (BBB) disruption and brain edema formation. Our results revealed that brain water content and BBB permeability increased significantly in the intoxicated mice. Meanwhile, the levels of phosphorylated p38 (p-p38) and inhibitory κBα (p-IκB), as well as the expression levels of MMP-9, c-jun, c-fos, and p65, also increased markedly in the brains of intoxicated mice. Conversely, the protein levels of ZO-1, occludin and claudin-5 in these mice decreased markedly, but their JAM-1 protein levels increased dramatically. Our results revealed that p-p38 levels in the brains of intoxicated mice were suppressed by pretreatment with a p38 inhibitor. In response to suppressed p-p38 levels, the brain water contents and DNA binding activities of NF-κB and AP-1, as well as the expression levels of MMP-9, c-jun, c-fos, p65, p-IκB and JAM-1, decreased, whereas the protein levels of ZO-1, occludin and claudin-5 increased markedly. Taken together, our findings indicated that the p38 signaling pathway might be activated and involved in the course of brain edema in 1,2-DCE-intoxicated mice.

积累的数据表明，在某些国家/地区使用的工业溶剂1,2-二氯乙烷（1,2-DCE）亚急性中毒会引起脑病，其中脑水肿是主要的病理变化。但是，其潜在机制尚不清楚。在本研究中，我们假设p38 MAPK（p38）信号通路可以在1,2-DCE中毒的小鼠中被激活，从而刺激转录因子，例如核因子-κB（NF-κB）和激活蛋白-1（AP-1），然后增强包括基质金属蛋白酶9（MMP-9）在内的促炎因子的表达，最终导致血脑屏障（BBB）破坏和脑水肿形成。我们的结果表明，中毒小鼠的脑含水量和血脑屏障通透性显着增加。同时，在中毒小鼠的大脑中，磷酸化的p38（p-p38）和抑制性κBα（p-IκB）的水平以及MMP-9，c-jun，c-fos和p65的表达水平也明显增加。相反，这些小鼠中ZO-1，occludin和claudin-5的蛋白质​​水平显着下降，但其JAM-1蛋白质水平却急剧上升。我们的结果表明，用p38抑制剂预处理可抑制中毒小鼠大脑中的p-p38水平。对抑制的p-p38水平，NF-κB和AP-1的脑含水量，DNA结合活性以及MMP-9，c-jun，c-fos，p65，p-IκB的表达水平有反应和JAM-1，减少，而ZO-1，occludin和claudin-5的蛋白质​​水平显着增加。在一起