|
|||||
|
|
Isoflurane post-conditioning contributes to anti-apoptotic effect after cerebral ischaemia in rats through the ERK5/MEF2D signaling pathway |
|
| Authors: | Qingtong Zhang Jiangwen Yin Feng Xu Jingwen Zhai Jieting Yin Mingyue Ge Wenyi Zhou Nian Li Xinlei Qin Yan Li Sheng Wang |
| Affiliation: | 1. Department of Anesthesiology, Lu’an Hospital Affiliated to Anhui Medical University, Lu’an People’s Hospital, Lu’an, China Contribution: Conceptualization (lead), Data curation (equal), Formal analysis (lead), Methodology (equal), Writing - original draft (lead), Writing - review & editing (equal);2. Department of Anesthesiology, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, China Contribution: Conceptualization (supporting), Data curation (equal), Formal analysis (equal), Methodology (equal);3. Department of Anesthesiology, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, China Contribution: Conceptualization (supporting), Data curation (equal), Methodology (lead);4. Department of Anesthesiology, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, China Contribution: Data curation (equal);5. Department of Anesthesiology, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, China Contribution: Data curation (equal), Methodology (equal);6. Department of Anesthesiology, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, China Contribution: Project administration (equal);7. Department of Anesthesiology, First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China |
| Abstract: | The mechanisms of brain protection during ischaemic reperfusion injury induced by isoflurane (ISO) post-conditioning are unclear. Myocyte enhancement factor 2 (MEF2D) has been shown to promote neural survival in a variety of models, in which multiple survival and death signals converge on MEF2D and modulate its activity. Here, we investigated the effect of MEF2D on the neuroprotective effects of ISO post-conditioning on rats after cerebral ischaemia/reperfusion (I/R) injury. Rats underwent middle cerebral artery occlusion (MCAO) surgery with ischaemia for 90 minutes and reperfusion for 24-48 hours. After MCAO, neurological status was assessed at 12, 24 and 48 hours by the Modified Neurological Severity Score (mNSS) test. The passive avoidance test (PAT) was used to assess cognition function. Histological and neuropathological evaluations were performed with HE staining and Nissl's staining, respectively. We measured the expression of MEF2D, ERK5, GFAP and caspase-3 by immunofluorescent staining and Western blotting, and TUNEL staining to assess the severity of apoptosis in hippocampal CA1 area. We found that MEF2D was involved in nerve protection after I/R injury, and post-treatment of ISO significantly promoted the phosphorylation of ERK5, increased MEF2D transcriptional activity, inhibited the expression of caspase-3 and played a role of brain protection. |
| Keywords: | ERK5 ischaemia/reperfusion injury isoflurane MEF2D neuroprotection |