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Open AccessArticle

CDDO-Me Attenuates Vasogenic Edema and Astroglial Death by Regulating NF-κB p65 Phosphorylations and Nrf2 Expression Following Status Epilepticus

1
Department of Anatomy and Neurobiology, College of Medicine, Hallym University, Chuncheon 24252, Korea
2
Institute of Epilepsy Research, College of Medicine, Hallym University, Chuncheon 24252, Korea
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(19), 4862; https://doi.org/10.3390/ijms20194862
Received: 11 September 2019 / Revised: 27 September 2019 / Accepted: 27 September 2019 / Published: 30 September 2019
(This article belongs to the Special Issue Epilepsy: From Molecular Mechanisms to Targeted Therapies 2.0)
2-Cyano-3,12-dioxo-oleana-1,9(11)-dien-28-oic acid methyl ester (CDDO-Me) is a triterpenoid analogue of oleanolic acid that has anti-inflammatory, antioxidant, and neuroprotective activities. In the present study, we evaluate the effects of CDDO-Me on serum extravasation and astroglial death in the rat piriform cortex (PC) induced by status epilepticus (a prolonged seizure activity, SE) in order to propose an underlying pharmacological mechanism of CDDO-Me and its availability for treatment of vasogenic edema. CDDO-Me effectively mitigated serum extravasation and a massive astroglial loss in the PC following SE. CDDO-Me abrogated tumor necrosis factor-α (TNF-α) synthesis in activated microglia by inhibiting nuclear factor-κB (NF-κB) p65 serine 276 phosphorylation. CDDO-Me also abolished NF-κB threonine 435 phosphorylation in endothelial cells and TNF-α-mediated-phosphatidylinositol-3-kinase (PI3K)/AKT/endothelial nitric oxide synthase (eNOS) signaling cascades, which trigger vasogenic edema following SE. Furthermore, CDDO-Me increased astroglial viability via the up-regulation of nuclear factor-erythroid 2-related factor 2 (Nrf2) expression. Therefore, our findings suggest that CDDO-Me may ameliorate SE-induced vasogenic edema formation by regulating NF-κB p65 phosphorylations in microglia as well as endothelial cells and enhancing Nrf2 expression in astrocytes, respectively. View Full-Text
Keywords: AKT; astrocyte; BBB; eNOS; microglia; PI3K; seizure; SMI-71 AKT; astrocyte; BBB; eNOS; microglia; PI3K; seizure; SMI-71
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MDPI and ACS Style

Kim, M.-J.; Park, H.; Choi, S.-H.; Kong, M.-J.; Kim, J.-E.; Kang, T.-C. CDDO-Me Attenuates Vasogenic Edema and Astroglial Death by Regulating NF-κB p65 Phosphorylations and Nrf2 Expression Following Status Epilepticus. Int. J. Mol. Sci. 2019, 20, 4862.

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