Taurine Protection against Endoplasmic Reticulum Stress in an Animal Stroke Model of Cerebral Artery Occlusion and Stroke Related conditions in Primary Neuronal Cell Culture

Abstract

Taurine has been shown to provide protection against neurological diseases, such as Huntington's and stroke. We have shown that taurine can provide effective protection against Endoplasmic Reticulum (ER) stress induced by excitotoxicity or oxidative stress in PC12 cell line or primary neuronal cell cultures. In this study, we employed hypoxia/reoxygenation conditions for primary cortical neuronal cell cultures as well as the model of rat focal Middle Cerebral Artery Occlusion (MCAO). Using taurine greatly increased cell viability in primary neuronal cell culture and decreased the infarct area of sections at 6mm from 47.42±9.86% to 26.76 ± 6.91% in the MCAO model. Furthermore levels of the ER stress protein markers GRP78, Caspase12, CHOP and p‐IRE‐1 which were markedly increased in both the in vitro and in vivo models, significantly declined after taurine administration, suggesting that taurine may exert neuroprotection functions in both models. Moreover, taurine could downregulate the ratio of cleaved ATF6 and full length ATF6 in both models. In the animal model of stroke, taurine induced an upregulation of the Bcl‐2/Bax ratio and downregulation of Caspase‐3 protein activity indicating that it attenuates apoptosis in the core of the ischemic infarct. Our results show not only taurine elicits neuroprotection through the activation of the ATF6 and the IRE1 pathways, but also it can reduce apoptosis in these modelsGrant Funding Source: 09KW‐11, Department of Health, State of Florida