Abstract
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.
Highlights
The protein expression levels of glial fibrillary acidic protein (GFAP) and soluble calcium-binding protein 100B (S100B) in the mouse brains of the three-day exposure group increased significantly compared with the control and the one-day exposure group, and those of GFAP in the two-day exposure group were significantly increased compared to the control and the one-day exposure group (Figure 1C,D)
These results revealed that subacute poisoning with 1,2-DCE could activate to the control, those in the three-day exposure group were significantly reduced compared to the two-day exposure groups, and did not differ significantly with the control group (Figure 1A,B)
5 of 18 were and the one-day exposure group, and those of GFAP in the two-day exposure group significantly increased compared to the control and the one-day exposure group (Figure 1C,D). These results revealed that subacute poisoning with 1,2-DCE could activate both astrocytes andfinally stimulate proinflammatory polarization of both astrocytesand and microglia, microglia, and stimulate thethe proinflammatory polarization of microgliaininmice
Summary
1,2-Dichloroethane (1,2-DCE), a synthetic halogenated hydrocarbon, is applied to the manufacture of polyvinyl chloride in the plastics industry, but it can cause brain edema under subacute exposure [1,2]. Damage, and edema formation in the brains of 1,2-DCE-intoxicated mice [3]. Studies up to now have demonstrated that neuroinflammation is associated with the pathogenesis of many brain diseases, and that it compounds neurotoxicity [4]. Emerging evidence indicates that crosstalk between microglia and astrocytes is fundamental to triggering neuroinflammation, and determines the fate of brain injury [5,6]. By releasing different signaling molecules, both microglia and astrocytes establish autocrine feedback and their bidirectional conversation for a tight reciprocal modulation during brain injury [7]. Microglia–astrocyte crosstalk is important for regulating microglial phenotypes and astrocytic functions, and is the determinant of the degree and duration of neuroinflammatory responses [8]
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