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Clin. Exp. Pharmacol. Physiol. · Oct 2015
Neuroprotective effects of a novel translocator protein (18 kDa) ligand, ZBD-2, against focal cerebral ischemia and NMDA-induced neurotoxicity.
- Xu-Bo Li, Hong-Liang Guo, Tian-Yao Shi, Le Yang, Min Wang, Kun Zhang, Yan-Yan Guo, Yu-Mei Wu, Shui-Bing Liu, and Ming-Gao Zhao.
- Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, China.
- Clin. Exp. Pharmacol. Physiol. 2015 Oct 1; 42 (10): 1068-74.
AbstractLigands of the translocator protein (18 kDa) (TSPO) have demonstrated rapid anxiolytic efficacy in stress responses and stress-related disorders. This protein is involved in the synthesis of endogenous neurosteroids including pregnenolone, dehydroepiandrosterone, and progesterone. These neurosteroids promote γ-aminobutyric acid-mediated neurotransmission in the central neural system (CNS). A TSPO ligand, N-benzyl-N-ethyl-2-(7,8-dihydro-7-benzyl-8-oxo-2-phenyl-9H-purin-9-yl) acetamide (ZBD-2) was recently synthesized. The purpose of the present study was to investigate the neuroprotective effects of ZBD-2 and. In cultured cortical neurons, treatment with ZBD-2 attenuated excitotoxicity induced by N-methyl-d-aspartate (NMDA) exposure. It significantly decreased the number of apoptotic cells by downregulating GluN2B-containing NMDA receptors (NMDARs), the ratio of Bax/Bcl-2, and levels of pro-caspase-3. Systemic treatment of ZBD-2 provided significant neuroprotection in mice subjected to middle cerebral artery occlusion. These findings provide direct evidence that neuroprotection by ZBD-2 is partially mediated by inhibiting GluN2B-containing NMDA receptor-mediated excitotoxicity. © 2015 Wiley Publishing Asia Pty Ltd.
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