Vitexin reduces epilepsy after hypoxic ischemia in the neonatal brain via inhibition of NKCC1.
Vitexin reduces epilepsy after hypoxic ischemia in the neonatal brain via inhibition of NKCC1.
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牡荆素通过抑制 NKCC1 减少新生儿大脑缺氧缺血后的癫痫
DOI：
10.1186/s12974-018-1221-6
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发表时间：
2018-06-20
影响因子：
9.3
通讯作者：
Peng BW
中科院分区：
文献类型：
--
作者：
Luo WD;Min JW;Huang WX;Wang X;Peng YY;Han S;Yin J;Liu WH;He XH;Peng BW
研究背景新生儿缺氧缺血性脑损伤是一种严重的中枢神经系统疾病，其特征是组织缺损和神经功能障碍。我们以前已经表明，牡荆素已被归因于各种药用特性，并已被证明在新生儿脑损伤模型中具有神经保护作用。在本研究中，我们继续加强和验证了对牡荆素的基本认识方法采用SD大鼠右侧颈总动脉结扎模型，观察大鼠脑微血管内皮细胞（RBMEC）Na+-K+-Cl−协同转运体1（NKCC 1）表达、血脑屏障通透性、细胞因子表达和中性粒细胞浸润，分别通过蛋白质印迹、q-PCR、流式细胞术（FCM）和免疫荧光法。此外，在自由活动的大鼠脑电活动记录脑电图（EEG）。结果我们的数据表明，NKCC 1的表达减弱牡荆素处理的大鼠相比，在HI组在体内的表达。用共聚焦显微镜、N-（乙氧羰基甲基）-6-甲氧基喹啉溴化盐和流式细胞术对RBMEC进行氧葡萄糖剥夺/复氧（OGD）以探讨NKCC 1和F-actin在细胞骨架形成中的作用。同时，用牡荆素处理有效地减轻OGD诱导的NKCC 1表达，其下调RBMEC中的F-actin表达。此外，牡荆素显着改善血脑屏障渗漏和救援紧密连接相关蛋白ZO-1的表达。此外，炎性细胞因子和中性粒细胞浸润的同时进行性下调，降低血脑屏障通透性在大鼠。牡荆素也显着抑制脑电活动在新生rates. ConclusionsTogether，这些结果证实，牡荆素有效地通过抑制炎症沿着改善血脑屏障的完整性，提高癫痫易感性。我们的研究为进一步开发牡荆素作为未成熟大脑中癫痫的有前途的治疗候选治疗提供了强有力的理论基础。
BackgroundNeonatal hypoxic-ischemic brain damage, characterized by tissue loss and neurologic dysfunction, is a leading cause of mortality and a devastating disease of the central nervous system. We have previously shown that vitexin has been attributed various medicinal properties and has been demonstrated to have neuroprotective roles in neonatal brain injury models. In the present study, we continued to reinforce and validate the basic understanding of vitexin (45 mg/kg) as a potential treatment for epilepsy and explored its possible underlying mechanisms.MethodsP7 Sprague-Dawley (SD) rats that underwent right common carotid artery ligation and rat brain microvascular endothelial cells (RBMECs) were used for the assessment of Na+-K+-Cl−co-transporter1 (NKCC1) expression, BBB permeability, cytokine expression, and neutrophil infiltration by western blot, q-PCR, flow cytometry (FCM), and immunofluorescence respectively. Furthermore, brain electrical activity in freely moving rats was recorded by electroencephalography (EEG).ResultsOur data showed that NKCC1 expression was attenuated in vitexin-treated rats compared to the expression in the HI group in vivo. Oxygen glucose deprivation/reoxygenation (OGD) was performed on RBMECs to explore the role of NKCC1 and F-actin in cytoskeleton formation with confocal microscopy,N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide, and FCM. Concomitantly, treatment with vitexin effectively alleviated OGD-induced NKCC1 expression, which downregulated F-actin expression in RBMECs. In addition, vitexin significantly ameliorated BBB leakage and rescued the expression of tight junction-related protein ZO-1. Furthermore, inflammatory cytokine and neutrophil infiltration were concurrently and progressively downregulated with decreasing BBB permeability in rats. Vitexin also significantly suppressed brain electrical activity in neonatal rats.ConclusionsTaken together, these results confirmed that vitexin effectively alleviates epilepsy susceptibility through inhibition of inflammation along with improved BBB integrity. Our study provides a strong rationale for the further development of vitexin as a promising therapeutic candidate treatment for epilepsy in the immature brain.
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影响因子：
3.7
作者：
Cleary RT;Sun H;Huynh T;Manning SM;Li Y;Rotenberg A;Talos DM;Kahle KT;Jackson M;Rakhade SN;Berry G;Jensen FE
通讯作者：
Jensen FE
影响因子：
--
作者：
Diniz TC;Silva JC;de Lima-Saraiva SR;Ribeiro FP;Pacheco AG;de Freitas RM;Quintans-Júnior LJ;Quintans Jde S;Mendes RL;Almeida JR
通讯作者：
Almeida JR
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
168.9
作者：
Gluckman, PD;Wyatt, JS;Gunn, AJ
通讯作者：
Gunn, AJ
影响因子：
9.8
作者：
Garzon-Muvdi T;Schiapparelli P;ap Rhys C;Guerrero-Cazares H;Smith C;Kim DH;Kone L;Farber H;Lee DY;An SS;Levchenko A;Quiñones-Hinojosa A
通讯作者：
Quiñones-Hinojosa A