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. 2022 Nov 23;13:1028002. doi: 10.3389/fphar.2022.1028002

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Copyright © 2022 Yuan, Lu, Lian, Zhao, Tang, Xu, Yao and Yu.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Experimental design and timeline. (A) Mice were subjected to a 9-min cardiac arrest surgery followed by cardiopulmonary resuscitation (CA/CPR) or a sham operation. Vehicle or AA147 (ATF6 activator; 2 mg/kg) was administered intraperitoneally 1 day before surgery and intravenously 15 min after the return of spontaneous circulation (ROSC) once again. The impact of AA147 on CA/CPR-induced oxidative stress and ER stress-related apoptosis as well as activation of the ATF6 and Nrf2 signaling pathways was detected at 1 day after CA/CPR. The effect of AA147 on neuroprotection after CA/CPR was evaluated at 3 days after CA/CPR. Groups: (1) Sham + Vehicle; (2) CA/CPR + Vehicle; (3) CA/CPR + AA147. (B) Ceapin-A7 (ATF6 inhibitor; 10 mg/kg) or ML385 (Nrf2 inhibitor; 30 mg/kg) was administered intraperitoneally 2 h before administration of AA147. The role of AA147-induced activation of the ATF6 or Nrf2 in the neuroprotective effect of AA147 against post-CA/CPR cerebral ischemia/reperfusion injury was assessed at respective timepoint. Groups: (1) CA/CPR + AA147 + Vehicle; (2) CA/CPR + AA147 + Ceapin-A7; (3) CA/CPR + AA147 + ML385.