Referenced in: none

Automatically associated channels: Slo1

Title: Cerebroside-A provides potent neuroprotection after cerebral ischaemia through reducing glutamate release and Ca²⁺ influx of NMDA receptors.

Authors: Lin Li, Rong Yang, Kaiyue Sun, Yinyang Bai, Zhuo Zhang, Libin Zhou, Zhi Qi, Jianhua Qi, Ling Chen

Journal, date & volume: Int. J. Neuropsychopharmacol., 2012 May , 15, 497-507

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21557879

Abstract
Excessive presynaptic glutamate release after cerebral ischaemia leads to neuronal death mainly through excessive calcium entry of N-methyl-D-aspartate receptors (NMDARs). Our recent study reported that cerebroside can open large-conductance Ca²⁺-activated K⁺ (BKCa) channels. The present study evaluated the effects of cerebroside-A (CS-A), a single molecule isolated from an edible mushroom, on brain injury after focal or global ischaemia in adult male mice and rats. We herein report that treatment with CS-A after 60-min middle cerebral artery occlusion dose-dependently reduced the cerebral infarction with at least a 6-h efficacious time-window, which was partially blocked by the BKCa channel blocker charybdotoxin (CTX). Treatment with CS-A after 20 min global cerebral ischaemia (four-vessel occlusion) significantly attenuated the death of pyramidal cells in hippocampal CA1 area, which was also sensitive to CTX. CS-A, by opening the BKCa channel, could prevent excessive glutamate release after oxygen-glucose deprivation (OGD). In addition, CS-A could inhibit NMDAR Ca²⁺ influx, which did not require the activation of the BKCa channel. Furthermore, CS-A blocked the OGD-induced NMDAR-dependent long-term potentiation in hippocampal CA1 region. These findings indicate that treatment with CS-A after stroke exerts potent neuroprotection through prevention of excessive glutamate release and reduction of Ca²⁺ influx through NMDARs.