CEFTRIAXONE ALLEVIATES EARLY BRAIN INJURY AFTER SUBARACHNOID HEMORRHAGE BY INCREASING EXCITATORY AMINO ACID TRANSPORTER 2 EXPRESSION VIA THE PI3K/AKT/NF-κB SIGNALING PATHWAY
CEFTRIAXONE ALLEVIATES EARLY BRAIN INJURY AFTER SUBARACHNOID HEMORRHAGE BY INCREASING EXCITATORY AMINO ACID TRANSPORTER 2 EXPRESSION VIA THE PI3K/AKT/NF-κB SIGNALING PATHWAY
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头孢曲松通过 PI3K/AKT/NF-kappa B 信号通路增加兴奋性氨基酸转运蛋白 2 的表达，减轻蛛网膜下腔出血后的早期脑损伤
DOI：
10.1016/j.neuroscience.2014.02.053
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发表时间：
2014-05-30
期刊：
影响因子：
3.3
通讯作者：
Qin, H.
中科院分区：
文献类型：
--
作者：
Feng, D.;Wang, W.;Qin, H.
蛛网膜下腔出血（SAH）后早期脑损伤（EBI）的特征是兴奋性氨基酸转运蛋白2 （EAAT2）表达减少和严重的氨基酸兴奋性毒性。本研究通过体外实验和SAH大鼠模型，探讨头孢曲松（CEF）对EBI的神经保护作用及其可能机制。CEF是一种上调EAAT2的有效化合物。腹腔内CEF治疗可显著改善SAH后的神经预后并减轻细胞外谷氨酸积聚。末端脱氧核苷酸转移酶介导的dutp -生物素缺口端标记法（TUNEL）染色和裂解caspase 3的Western blot分析显示，CEF减少了SAH后海马神经元的凋亡。免疫荧光染色和Western blotting显示，CEF显著逆转SAH后EAAT2表达的下调。在Morris水迷宫（MWM）实验中，CEF显著改善了sah诱导的空间学习记忆和参考记忆的认知功能障碍。在体外和体内实验中，CEF促进海马星形胶质细胞p65的核易位和Akt的激活。这些发现表明，CEF可能通过调节PI3K/Akt/NF-kappa B信号通路，对SAH后EBI具有显著的保护作用。(c) 2014 ibro。Elsevier Ltd.出版。版权所有。
Early brain injury (EBI) after subarachnoid hemorrhage (SAH) is characterized by a reduction in excitatory amino acid transporter 2 (EAAT2) expression and severe amino acid excitotoxicity. The aim of this study was to explore the neuroprotective effect of ceftriaxone (CEF), a potent compound that up-regulates EAAT2, against EBI and the potential mechanisms using in vitro experiments and a rat model of SAH. Intracisternal treatment with CEF significantly improved neurological outcomes and alleviated extracellular glutamate accumulation after SAH. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) staining and Western blot analysis of cleaved caspase 3 showed that CEF decreased hippocampal neuronal apoptosis following SAH. Immunofluorescent staining and Western blotting revealed that CEF significantly reversed the down-regulation of EAAT2 expression following SAH. In Morris water maze (MWM) tests, CEF remarkably ameliorated the SAH-induced cognitive dysfunction in spatial learning memory and reference memory. CEF promoted the nuclear translocation of p65 as well as the activation of Akt in hippocampal astrocytes in vitro and in vivo. These findings suggest that CEF may exert significant protective effects against EBI following SAH by modulating the PI3K/Akt/NF-kappa B signaling pathway. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.