Roles of Crosstalk between Astrocytes and Microglia in Triggering Neuroinflammation and Brain Edema Formation in 1,2-Dichloroethane-Intoxicated Mice

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.