Methylprednisolone sodium succinate reduces BBB disruption and inflammation in a model mouse of intracranial haemorrhage
Methylprednisolone sodium succinate reduces BBB disruption and inflammation in a model mouse of intracranial haemorrhage
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甲基强的松龙琥珀酸钠可减少颅内出血模型小鼠的血脑屏障破坏和炎症
DOI：
10.1016/j.brainresbull.2016.10.007
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发表时间：
2016-10-01
影响因子：
3.8
通讯作者：
Zhang, Yan
中科院分区：
文献类型：
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作者：
Cheng, Shiqi;Gao, WeiWei;Zhang, Yan
颅内出血（ICH）后血脑屏障（BBB）的炎症和破坏引起脑水肿和继发性脑损伤，与患者预后密切相关。甲泼尼龙琥珀酸钠（MPSS）是一种免疫抑制剂，广泛应用于多种疾病的抗炎治疗。在这项研究中，我们研究了MPSS对脑出血模型小鼠的炎症和血脑屏障破坏的影响。将胶原酶注射到雄性C57/BL小鼠的右侧纹状体中诱导ICH。用伊文思蓝法测定血脑屏障通透性，用脑含水量测定脑水肿程度。通过Western Blot检测NF-κ B、TLR 4、occludin、ZO-1、IL-1 β、TNF-α、Bax和Bcl-2的表达。免疫组化法检测中性粒细胞、小胶质细胞的表达，TUNEL法和NeuN法检测神经元凋亡。ICH后给予MPSS显著降低BBB的通透性和脑水肿，并上调ZO-1和Occludin的表达。MPSS抑制炎症反应，包括减少促炎细胞因子（IL-1 β，TNF-α），抑制中性粒细胞浸润和小胶质细胞活化。这伴随着TLR 4/NF-κ B信号通路的减弱激活。此外，MPSS通过增加Bcl-2的表达和减少Bax的表达来减少神经元凋亡。MPSS抑制炎症反应，减弱BBB的破坏和减少神经元凋亡，有助于减少ICH后继发性脑损伤。这些结果表明，MPSS可能是一种潜在的治疗ICH。(C)2016 Elsevier Inc. All rights reserved.
Inflammation and disruption of the blood-brain barrier (BBB) cause oedema and secondary brain injury after intracranial haemorrhage (ICH), which is closely related to patient prognosis. Methylprednisolone sodium succinate (MPSS), a well-known immunosuppressive agent, is widely applied in many diseases to inhibit inflammation. In this study, we investigated the effect of MPSS on inflammation and disruption of the BBB in a model mouse of ICH. ICH was induced by injecting collagenase into the right striatum of male C57/BL mice. Permeability of BBB was measured with Evans Blue assay and brain oedema was detected by measurement of brain water content. Expressions of NF-kappa B, TLR4, occludin, ZO-1, IL-1 beta, TNF-alpha, Bax, and Bcl-2 were determined by Western Blot. Neutrophils, microglia were measured by immunohistochemistry staining, neuronal apoptosis was measured by TUNEL and NeuN co-stained. Administration of MPSS post-ICH significantly reduced permeability of the BBB and brain oedema and upregulated expression of ZO-1 and Occludin. MPSS inhibited inflammatory responses, including reducing proinflammatory cytokines (IL-1 beta, TNF-alpha), suppressing infiltration of neutrophils and activation of microglia. This was accompanied by attenuated activation of the TLR4/NF-kappa B signalling pathway. In addition, MPSS reduced neuronal apoptosis through increasing Bcl-2 expression and reducing Bax expression. MPSS suppressed inflammatory responses, attenuated disruption of the BBB and reduced neuronal apoptosis, contributing to reduction of secondary brain injury after ICH. These results suggest that MPSS may be a potential therapy for ICH. (C) 2016 Elsevier Inc. All rights reserved.