Referenced in: none

Automatically associated channels: Slo1

Title: Neuroprotective effects of a novel translocator protein (18 kDa) ligand, ZBD-2, against focal cerebral ischemia and NMDA-induced neurotoxicity.

Authors: Xu-Bo Li, Hong-Liang Guo, Tian-yao Shi, Le Yang, Min Wang, Kun Zhang, Yan-Yan Guo, Yu-Mei Wu, Shui-Bing Liu, Ming-Gao Zhao

Journal, date & volume: Clin. Exp. Pharmacol. Physiol., 2015 Oct , 42, 1068-74

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/26174423

Abstract
Ligands 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.