Leptomycin B ameliorates vasogenic edema formation induced by status epilepticus via inhibiting p38 MAPK/VEGF pathway
Leptomycin B ameliorates vasogenic edema formation induced by status epilepticus via inhibiting p38 MAPK/VEGF pathway
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DOI：
10.1016/j.brainres.2016.09.023
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发表时间：
2016-11-15
期刊：
影响因子：
2.9
通讯作者：
Kang, Tae-Cheon
中科院分区：
文献类型：
--
作者：
Kim, Duk-Soo;Min, Su-Ji;Kang, Tae-Cheon
脑损伤期间血脑屏障（BBB）的破坏导致血管源性水肿，这是致癫痫过程的主要步骤之一。然而，有关血管源性水肿形成的信号通路尚未阐明。在本研究中，癫痫持续状态（SE）导致血管内皮生长因子（VEGF）的过度表达伴随着BBB的完整性在大鼠梨状皮质的损失。瘦霉素B（LMB，染色体区域维持抑制剂1）可减弱SE诱导的血管源性水肿形成。LMB的这种抗水肿作用与抑制VEGF过度表达以及p38丝裂原活化蛋白激酶（MAPK）磷酸化有关。此外，513202190（p38 MAPK抑制剂）可改善SE诱导的血管源性水肿和VEGF过度表达。提示p38 MAPK/VEGF信号通路可能参与SE后血脑屏障的破坏。因此，我们认为p38 MAPK/VEGF轴可能是多种神经系统疾病血管源性水肿的治疗靶点之一。(C)© 2016 Elsevier B. V.版权所有。
The blood-brain barrier (BBB) disruption during brain insults leads to vasogenic edema as one of the primary steps in the epileptogenic process. However, the signaling pathway concerning vasogenic edema formation has not been clarified. In the present study, status epilepticus (SE) resulted in vascular endothelial growth factor (VEGF) over-expression accompanied by loss of BBB integrity in the rat piriform cortex. Leptomycin B (LMB, an inhibitor of chromosome region maintenance 1) attenuated SE-induced vasogenic edema formation. This anti-edema effect of LMB was relevant to inhibitions of VEGF over expression as well as p38 mitogen-activated protein kinase (MAPK) phosphorylation. Furthermore, 513202190 (a p38 MAPK inhibitor) ameliorated vasogenic edema and VEGF over-expression induced by SE. These findings indicate that p38 MAPK/VEGF signaling pathway may be involved in BBB disruption following SE. Thus, we suggest that p38 MAPK/VEGF axis may be one of therapeutic targets for vasogenic edema in various neurological diseases. (C) 2016 Elsevier B.V. All rights reserved.