Endoplasmic reticulum stress is associated with neuroprotection against apoptosis via autophagy activation in a rat model of subarachnoid hemorrhage.

Abstract

Endoplasmic reticulum (ER) stress might play an important role in a range of neurological diseases; however, this phenomenon's role in subarachnoid hemorrhage (SAH) remains unclear. In this study, we explored the potential role of endoplasmic reticulum stress in early brain injury following SAH.84 rats were used for an endovascular perforation-induced subarachnoid hemorrhage model. The rats were intraperitoneally pretreated with the ER stress inducer tunicamycin (Tm) or with the inhibitor tauroursodeoxycholic acid (TUDCA) before SAH onset. An intracerebral ventricular infusion of autophagy inhibitor 3-methyladenine (3-MA) was also used to determine the relation between autophagy and ER stress in early brain injury following SAH. At 24h, rats were neurologically evaluated, and their brains were extracted for molecular biological and histological studies. ER stress was activated in rats after 24h of SAH. Enhanced ER stress via Tm pretreatment significantly improved neurological deficits, attenuated the expression of pro-apoptotic molecules of caspase-3 and reduced the number of TUNEL-positive cells. In contrast, the ER stress inhibitor TUDCA aggravated neurological deficits and apoptotic cell death. Western blot analysis revealed that levels of the autophagic protein Beclin 1 and the ratio of LC3-II to LC3-I were both increased by Tm infusion and reduced by TUDCA administration. The suppression of autophagic activity with 3-MA attenuated Tm-induced anti-apoptotic effects. Our study indicates that ER stress alleviates early brain injury following SAH via inhibiting apoptosis. This neuroprotective effect is most likely exerted by autophagy activation.

• Authors: Feng Yan, Jianru Li, Jingyin Chen, Qiang Hu, Chi Gu, Wang Lin, Gao Chen
• Journal: Neuroscience letters (Neurosci Lett) Vol. 563 Pg. 160-5 (Mar 20 2014) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 24513235 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Tunicamycin
• Taurochenodeoxycholic Acid
• ursodoxicoltaurine

Topics

• Animals
• Apoptosis (physiology)
• Autophagy (physiology)
• Endoplasmic Reticulum Stress (drug effects, physiology)
• Male
• Rats, Sprague-Dawley
• Subarachnoid Hemorrhage (metabolism, pathology, physiopathology)
• Taurochenodeoxycholic Acid (pharmacology)
• Tunicamycin (pharmacology)