title: Role of Endoplasmic Reticulum Stress in Brain Damage After Cardiopulmonary Resuscitation in Rats.
abstract: Postcardiac arrest syndrome yields poor neurological outcomes, but the mechanisms underlying this condition remain poorly understood. This study investigated whether endoplasmic reticulum (ER) stress-mediated apoptosis is induced in injured brain after resuscitation. Sprague-Dawley rats were subjected to 6 min of cardiac arrest (CA) and then resuscitated successfully. In the first experiment, animals were sacrificed 1, 3, 6, 12, or 24 h (n = 3 per group) after successful cardiopulmonary resuscitation. Brain tissues were analyzed by real-time polymerase chain reaction and Western blotting. In the second experiment, either dimethyl sulfoxide or salubrinal (Sal; 1 mg/kg), an ER stress inhibitor, was injected 30 min before the induction of CA (n = 10 per group). Neurological deficits were evaluated 24 h after CA. Brain specimens were analyzed using electron microscopy, terminal deoxynucleotidyl transferase dUTP nick end labeling assays and immunohistochemistry. We found that the messenger RNA and protein levels of glucose-regulated protein 78, X-box binding protein 1, C/EBP homologous protein, and caspase 12 were significantly elevated after resuscitation. We also observed that rats treated with Sal exhibited an improved neurological deficit score (32.3 ± 15.5 in the Sal group vs. 49.8 ± 20.9 in controls, P < 0.05). In addition, morphological improvements in the hippocampal ER were observed in the Sal group compared with the dimethyl sulfoxide group 24 h after reperfusion. Furthermore, in situ immunostaining revealed that markers of ER stress were significantly inhibited by Sal pretreatment. Our findings suggested that ER stress and the associated apoptotic pathways were activated in the hippocampus after resuscitation. Administration of Sal 30 min before cardiopulmonary resuscitation ameliorated neurological dysfunction 24 h after CA, possibly through the inhibition of ER stress after postresuscitation brain injury.
authors.affiliation: *Emergency Department, and †Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China; and ‡Department of Otolaryngology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
authors.forename: Jincheng
authors.initials: J
authors.lastname: Zhang
authors.forename: Xuemeng
authors.initials: X
authors.lastname: Xie
authors.forename: Hao
authors.initials: H
authors.lastname: Pan
authors.forename: Ziqian
authors.initials: Z
authors.lastname: Wu
authors.forename: Wen
authors.initials: W
authors.lastname: Lu
authors.forename: Guangtian
authors.initials: G
authors.lastname: Yang
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001930:Brain Injuries / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016887:Cardiopulmonary Resuscitation / Q000009:adverse effects*; D059865:Endoplasmic Reticulum Stress; D005786:Gene Expression Regulation; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D009419:Nerve Tissue Proteins