Roles of Crosstalk between Astrocytes and Microglia in Triggering Neuroinflammation and Brain Edema Formation in 1,2-Dichloroethane-Intoxicated Mice.
Roles of Crosstalk between Astrocytes and Microglia in Triggering Neuroinflammation and Brain Edema Formation in 1,2-Dichloroethane-Intoxicated Mice.
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星形胶质细胞和小胶质细胞之间的串扰在触发 1,2-二氯乙烷中毒小鼠神经炎症和脑水肿形成中的作用
作者：
Yang J;Wang T;Jin X;Wang G;Zhao F;Jin Y
我们以前曾报道，星形胶质细胞和小胶质细胞的激活可能导致促炎介质的过度产生，从而导致1，2-二氯乙烷(1，2-DCE)中毒小鼠的神经炎症和脑水肿。在这项研究中，我们进一步假设星形胶质细胞-小胶质细胞串扰可能会引发神经炎症，并导致1，2-二氯乙烷中毒小鼠的脑水肿。本研究首次揭示了1，2-二氯乙烷亚急性中毒可引起小胶质细胞的促炎极化，而小胶质细胞激活的特异性抑制剂米诺环素可减弱小胶质细胞中离子钙结合接头分子1、分化簇11b、胶质纤维酸性蛋白、可溶性钙结合蛋白100B、肿瘤坏死因子α、白介素6、诱导型一氧化氮合酶、血管细胞黏附分子1、细胞间黏附分子1、细胞间黏附分子1、细胞间黏附分子1的表达水平。基质金属蛋白酶-9、Toll样受体4、MyD88和p-p65的表达，改善occludin和claudin 5的蛋白表达水平；我们还观察了1，2-二氯乙烷中毒小鼠脑含水量的变化，并对脑水肿进行了病理观察。此外，预先给予反应性星形胶质细胞抑制物氟柠檬酸还可逆转1，2-二氯乙烯中毒小鼠脑内胶质纤维酸性蛋白、S100b、Iba-1、CD11b、肿瘤坏死因子-α、IL-6、诱导型一氧化氮合酶、血管细胞黏附分子-1、细胞间黏附分子-1、基质金属蛋白酶-9、阻滞素和claudin5蛋白表达水平的变化。此外，褪黑素是一种著名的抗炎药物，它也可以减轻1，2-二氯乙烷中毒小鼠脑内的上述变化。总之，本研究的结果表明，小胶质细胞的激活可能在引发神经炎症中发挥重要作用，从而可能有助于脑水肿的形成；此外，研究结果表明，反应性星形胶质细胞和激活的小胶质细胞之间的分子串扰可能放大了神经炎性反应，从而可能导致1，2-DCE中毒小鼠的继发性脑损伤。
We have previously reported that the activation of astrocytes and microglia may lead to the overproduction of proinflammatory mediators, which could induce neuroinflammation and cause brain edema in 1,2-dichloroethane (1,2-DCE)-intoxicated mice. In this research, we further hypothesized that astrocyte–microglia crosstalk might trigger neuroinflammation and contribute to brain edema in 1,2-DCE-intoxicated mice. The present research revealed, for the first time, that subacute intoxication with 1,2-DCE might provoke the proinflammatory polarization of microglia, and pretreatment with minocycline, a specific inhibitor of microglial activation, may attenuate the enhanced protein levels of ionized calcium-binding adapter molecule1 (Iba-1), cluster of differentiation 11b (CD11b), glial fibrillary acidic protein (GFAP), soluble calcium-binding protein 100B (S100B), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), inducible nitric oxide synthase (iNOS), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), matrix metalloproteinase-9 (MMP-9), Toll-like receptor 4 (TLR4), MyD88, and p-p65, and ameliorate the suppressed protein expression levels of occludin and claudin 5; we also observed changes in water content and made pathological observations on edema in the brains of 1,2-DCE-intoxicated mice. Moreover, pretreatment with fluorocitrate, an inhibitor of reactive astrocytes, could also reverse the alteration in protein expression levels of GFAP, S100B, Iba-1, CD11b, TNF-α, IL-6, iNOS, VCAM-1, ICAM-1, MMP-9, occludin, and claudin 5 in the brain of 1,2-DCE intoxicated mice. Furthermore, pretreatment with melatonin, a well-known anti-inflammatory drug, could also attenuate the above-mentioned changes in the brains of 1,2-DCE-intoxicated mice. Altogether, the findings from this research indicated that microglial activation might play an important role in triggering neuroinflammation, and hence may contribute to brain edema formation; additionally, the findings suggested that molecular crosstalk between reactive astrocytes and activated microglia may amplify the neuroinflammatory reaction, which could induce secondary brain injury in 1,2-DCE-intoxicated mice.
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