Poloxamer-188 Can Attenuate Blood-Brain Barrier Damage to Exert Neuroprotective Effect in Mice Intracerebral Hemorrhage Model
Poloxamer-188 Can Attenuate Blood-Brain Barrier Damage to Exert Neuroprotective Effect in Mice Intracerebral Hemorrhage Model
复制标题
Poloxamer-188 可减轻血脑屏障损伤，对小鼠脑出血模型发挥神经保护作用
DOI：
10.1007/s12031-014-0313-8
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发表时间：
2015-01-01
影响因子：
3.1
通讯作者：
Chen, Yijiu
中科院分区：
文献类型：
--
作者：
Wang, Tao;Chen, Xiping;Chen, Yijiu
血脑屏障的破坏和脑水肿的形成在脑出血所致的继发性神经元死亡和神经功能障碍中起重要作用。泊洛沙姆188(P188)是一种多嵌段共聚物表面活性剂，已被证明能够封闭受损的细胞膜，减少神经细胞死亡。在本研究中，我们探讨了p188是否对脑出血有保护作用及其机制。雄性ICR小鼠左侧纹状体注射IV型胶原酶(诱导ICH)和生理盐水(假手术组)。结果表明，脑出血后24 h和72 h尾静脉注射p188-12 mg可明显改善大鼠的神经症状和脑水肿，降低血脑屏障通透性，减少细胞损伤和损伤体积。此外，p188维持脑出血后72h紧密连接蛋白(TJ)包括claudin-5、occludin和zonula occludens-1的蛋白水平，并逆转核因子-kappaB(NF-kappaB)、基质金属蛋白酶(MMP2)和MMP9蛋白表达的增加。免疫荧光显示，p188处理后TJ蛋白的结构发生了连续的线性重排。因此，本研究得出结论：p188对脑出血具有保护作用，其保护作用与其通过抑制核因子-kappaB-MMPs介导的TJ蛋白的降解而阻止血脑屏障的破坏有关。
Blood-brain barrier (BBB) disruption and brain edema formation play important roles in the secondary neuronal death and neurological dysfunction induced by intracerebral hemorrhage (ICH). Poloxamer 188 (P188), a multiblock copolymer surfactant, has been shown to be capable of sealing damaged cell membranes and decrease neuronal cell death. In this study, we explored whether P188 had a protective effect against ICH and its underlying mechanisms. Male ICR mice were subjected to infusion of type IV collagenase (to induce ICH) of saline (for shams) into the left striatum. The results showed that P188-12 mg post-treatment by tail intravenous injection significantly ameliorated the neurological symptoms and brain edema, attenuated BBB permeability, and decreased cell insults and injury volume at 24 and 72 h after ICH. Furthermore, P188 maintained the protein levels of tight junction (TJ) proteins including claudin-5, occludin, and zonula occludens-1, and reversed the increases of nuclear factor-kappaB (NF-kappa B), matrix metalloproteinase (MMP)-2, and MMP-9 protein expression at 72 h post ICH. Immunofluorescence showed P188 treatment rearranged the structure of TJ proteins in a continuous and linear pattern. Therefore, the present study concludes that P188 can protect against ICH, and the protective effect was associated with preventing BBB disruption through NF-kappa B-MMPs-mediated TJ proteins degradation.