Kim Duk-Soo, Min Su-Ji, Kim Min-Ju, Kim Ji-Eun, Kang Tae-Cheon
Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si 31538, South Korea.
Department of Anatomy and Neurobiology, College of Medicine, Hallym University, Chuncheon 24252, South Korea; Institute of Epilepsy Research, College of Medicine, Hallym University, Chuncheon 24252, South Korea.
Brain Res. 2016 Nov 15;1651:27-35. doi: 10.1016/j.brainres.2016.09.023. Epub 2016 Sep 19.
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, SB202190 (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.
脑损伤期间血脑屏障（BBB）的破坏会导致血管源性水肿，这是致痫过程中的主要步骤之一。然而，关于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）导致大鼠梨状皮质中血管内皮生长因子（VEGF）过度表达，同时血脑屏障完整性丧失。雷帕霉素B（LMB，一种染色体区域维持蛋白1抑制剂）减轻了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，SB202190（一种p38 MAPK抑制剂）改善了SE诱导的血管源性水肿和VEGF过度表达。这些发现表明，p38 MAPK/VEGF信号通路可能参与了SE后的血脑屏障破坏。因此，我们认为p38 MAPK/VEGF轴可能是各种神经疾病中血管源性水肿的治疗靶点之一。
