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Taurine 8 pp 241-258 | Cite as

The Mechanism of Taurine Protection Against Endoplasmic Reticulum Stress in an Animal Stroke Model of Cerebral Artery Occlusion and Stroke-Related Conditions in Primary Neuronal Cell Culture

Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 776)

Abstract

Taurine is an inhibitory neurotransmitter and is one of the most abundant amino acids present in the mammalian nervous system. Taurine has been shown to provide protection against neurological diseases, such as Huntington’s disease, Alzheimer’s disease, and stroke. Ischemic stroke is one of the leading causes of death and disability in the world. It is generally believed that ischemia-induced brain injury is largely due to excessive release of glutamate resulting in excitotoxicity and cell death. Despite extensive research, there are still no effective interventions for stroke. Recently, 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 an in vitro model of stroke as well as the in vivo model of rat focal middle cerebral artery occlusion (MCAO). Our data showed that when primary neuronal cultures were first subjected to hypoxic conditions (0.3%, 24 h) followed by reoxygenation (21%, 24–48 h), the cell viability was greatly reduced. In the animal model of stroke (MCAO), we found that 2 h ischemia followed by 4 days reperfusion resulted in an infarct of 47.42 ± 9.86% in sections 6 mm from the frontal pole. Using taurine greatly increased cell viability in primary neuronal cell culture and decreased the infarct area of sections at 6 mm to 26.76 ± 6.91% in the MCAO model. Furthermore, levels of the ER stress protein markers GRP78, caspase-12, 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 models.

Keywords

Endoplasmic Reticulum Stress Middle Cerebral Artery Occlusion Infarct Volume Primary Neuronal Culture Local Cerebral Blood Flow 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

ER

Endoplasmic reticulum

MCAO

Middle cerebral artery occlusion

GRP78

Glucose-regulated protein 78

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Biomedical Sciences, Charles E. Schmidt College of MedicineFlorida Atlantic UniversityBoca RatonUSA
  2. 2.Centre of Complex Systems and Brain SciencesFlorida Atlantic UniversityBoca RatonUSA
  3. 3.Department of Neurology and Sleep Center, Shung Ho HospitalTaipei Medical UniversityTaipeiTaiwan
  4. 4.Program in Integrative BiologyFlorida Atlantic UniversityBoca RatonUSA

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