PMID- 37897375 OWN - NLM STAT- MEDLINE DCOM- 20240209 LR - 20240210 IS - 1097-0029 (Electronic) IS - 1059-910X (Linking) VI - 87 IP - 3 DP - 2024 Mar TI - Remote ischemic postconditioning alleviates cerebral ischemic injury through SERCA2/endoplasmic reticulum stress-mediated apoptosis. PG - 424-433 LID - 10.1002/jemt.24431 [doi] AB - Remote ischemic postconditioning (RIPostC) alleviates brain ischemic injury through several pathways, including endoplasmic reticulum (ER) stress modulation. Sarco endoplasmic reticulum Ca(2+) -ATPase(SERCA2) which plays vital role in calcium homeostasis regulation could modulate ER stress logically. This study aimed to investigate whether RIPostC exerts its neuroprotective effect by reducing ER stress mediated by SERCA2. Male SD rats underwent transient middle cerebral artery occlusion (tMCAO) for 2 h followed by reperfusion, with the RIPostC group undergoing 3 cycles of bilateral femoral artery clamping and reperfusion at the beginning of reperfusion. Stroke outcome was assessed based on infarct volume and neurological function evaluation. Protein levels of SERCA2 and other ER stress markers were measured using Western blotting, immunofluorescence, and immunohistochemistry techniques. Compared to the sham group, we observed that RIPostC can effectively reduce cerebral infarct volume after I/R (34.55%: 21.03%; p = .004) and improve neurological function deficit (9.67:12.5; p = .029). Additionally, RIPostC increased SERCA2 protein expression and decreased the protein level of glucose-regulated protein 78 (GRP78), phosphorylation of eukaryotic translation initiation factor 2alpha (p-eIF2alpha) and CCAAT/EBP homologous protein (CHOP). Furthermore, B-cell lymphoma-2 (Bcl-2) expression was increased, while Bcl-2-associated X protein (Bax) and cleaved-caspase-3 was decreased in response to application of RIPostC. Our results suggest that RIPostC improves the prognosis of tMCAO rats, possibly by inhibiting the ER stress mediated by SERCA2, facilitating apoptosis downregulation. The significance of this study is to provide a theoretical basis for further exploring the protective mechanism of ischemic stroke by RIPostC. RESEARCH HIGHLIGHTS: Our results suggest that RIPostC improves the prognosis of tMCAO rats, possibly by inhibiting the ER stress mediated by SERCA2, facilitating apoptosis downregulation, thus achieving a neuroprotective effect. CI - (c) 2023 Wiley Periodicals LLC. FAU - Chen, Wanying AU - Chen W AD - Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. FAU - Li, Mengmeng AU - Li M AD - Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. FAU - Lei, Xiangyu AU - Lei X AD - Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. FAU - Cheng, Yawen AU - Cheng Y AD - Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. FAU - Wu, Xiaoyu AU - Wu X AD - Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. FAU - Sun, Xinyue AU - Sun X AD - Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. FAU - Wu, Yixuan AU - Wu Y AD - Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. FAU - Li, Zhiheng AU - Li Z AD - Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. FAU - Luo, Guogang AU - Luo G AD - Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. FAU - Wei, Meng AU - Wei M AUID- ORCID: 0009-0004-5765-7414 AD - Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. LA - eng GR - 2019QN-13/First Affiliated Hospital of Xi'an Jiaotong University Foundation/ GR - 2022JQ-987/Natural Science Foundation of Shaanxi Province/ GR - XJTU1AF2021CRF-003/The Clinical Research Award of the First Affiliated Hospital of Xi'an Jiaotong University, China/ GR - XJTU1AF-CRF-2020-015/The Clinical Research Award of the First Affiliated Hospital of Xi'an Jiaotong University, China/ PT - Journal Article DEP - 20231028 PL - United States TA - Microsc Res Tech JT - Microscopy research and technique JID - 9203012 RN - 0 (Neuroprotective Agents) SB - IM MH - Rats MH - Male MH - Animals MH - *Ischemic Postconditioning MH - Rats, Sprague-Dawley MH - Signal Transduction MH - *Neuroprotective Agents MH - Apoptosis MH - Endoplasmic Reticulum Stress OTO - NOTNLM OT - endoplasmic reticulum stress OT - remote ischemic postconditioning OT - sarco endoplasmic reticulum Ca2+-ATPase OT - transient middle cerebral artery occlusion EDAT- 2023/10/29 06:42 MHDA- 2024/02/09 06:42 CRDT- 2023/10/28 09:03 PHST- 2023/09/18 00:00 [revised] PHST- 2023/05/29 00:00 [received] PHST- 2023/09/19 00:00 [accepted] PHST- 2024/02/09 06:42 [medline] PHST- 2023/10/29 06:42 [pubmed] PHST- 2023/10/28 09:03 [entrez] AID - 10.1002/jemt.24431 [doi] PST - ppublish SO - Microsc Res Tech. 2024 Mar;87(3):424-433. doi: 10.1002/jemt.24431. Epub 2023 Oct 28.