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Dexmedetomidine alleviates cerebral ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress dependent apoptosis through the PERK-CHOP-Caspase-11 pathway.
Brain Res. 2018 12 15; 1701:246-254.BR

Abstract

Dexmedetomidine (Dex) has the neuroprotective effect on cerebral ischemia-reperfusion injury (CIRI). But the mechanism is not yet clear. In this study, we established a model of middle cerebral artery occlusion (MCAO) and treated primary cortical neurons with oxygen glucose deprivation (OGD), followed by Dex treatment. Neurological protection of Dex was then assessed by neurological deficit score, brain edema, TTC staining, TUNEL assay, Western blot analysis, immunohistochemistry, and RT-PCR. The results showed that Dex significantly reduced the neurological deficit score, brain edema and cerebral infarction area due to CIRI. After Dex treatment, the expression levels of ER stress-related apoptosis pathway proteins (GRP78, p-PERK, CHOP and Cleaved-caspase-3) were significantly decreased and the apoptosis of brain cells was also significantly reduced. Immunohistochemistry showed that expression and nuclear localization of CHOP decreased significantly after the application of Dex. The downstream apoptotic protein caspase-11 mediated by PERK-CHOP was also markedly inhibited by Dex. In conclusion, our results suggested that Dex reduced ER stress-induced apoptosis after CIRI. Its protective mechanism may be related to PERK-CHOP-Caspase-11 dependent signaling pathway.

Authors+Show Affiliations

Department of Anaesthesiology, Tianjin Fourth Central Hospital, The Fourth Central Hospital Affiliated to Nankai University, The Fourth Center Clinical College of Tianjin Medical University, Tianjin 300140, China.Department of Critical Care Medicine, Tianjin Fourth Central Hospital, The Fourth Central Hospital Affiliated to Nankai University, The Fourth Center Clinical College of Tianjin Medical University, Tianjin 300140, China. Electronic address: fqprofessor@126.com.Department of Anaesthesiology, Tianjin Fourth Central Hospital, The Fourth Central Hospital Affiliated to Nankai University, The Fourth Center Clinical College of Tianjin Medical University, Tianjin 300140, China.Department of Anaesthesiology, Tianjin Fourth Central Hospital, The Fourth Central Hospital Affiliated to Nankai University, The Fourth Center Clinical College of Tianjin Medical University, Tianjin 300140, China.Department of Anaesthesiology, Tianjin Fourth Central Hospital, The Fourth Central Hospital Affiliated to Nankai University, The Fourth Center Clinical College of Tianjin Medical University, Tianjin 300140, China.Department of Anaesthesiology, Tianjin Fourth Central Hospital, The Fourth Central Hospital Affiliated to Nankai University, The Fourth Center Clinical College of Tianjin Medical University, Tianjin 300140, China.Department of Anaesthesiology, Tianjin Fourth Central Hospital, The Fourth Central Hospital Affiliated to Nankai University, The Fourth Center Clinical College of Tianjin Medical University, Tianjin 300140, China.Department of Anaesthesiology, Tianjin Fourth Central Hospital, The Fourth Central Hospital Affiliated to Nankai University, The Fourth Center Clinical College of Tianjin Medical University, Tianjin 300140, China.Central Laboratory, Tianjin Fourth Central Hospital, The Fourth Central Hospital Affiliated to Nankai University, The Fourth Center Clinical College of Tianjin Medical University, Tianjin 300140, China.Department of Cardiology, Tianjin Fourth Central Hospital, The Fourth Central Hospital Affiliated to Nankai University, The Fourth Center Clinical College of Tianjin Medical University, Tianjin 300140, China. Electronic address: fengshitian0801011@126.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30201260

Citation

Liu, Chong, et al. "Dexmedetomidine Alleviates Cerebral Ischemia-reperfusion Injury By Inhibiting Endoplasmic Reticulum Stress Dependent Apoptosis Through the PERK-CHOP-Caspase-11 Pathway." Brain Research, vol. 1701, 2018, pp. 246-254.
Liu C, Fu Q, Mu R, et al. Dexmedetomidine alleviates cerebral ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress dependent apoptosis through the PERK-CHOP-Caspase-11 pathway. Brain Res. 2018;1701:246-254.
Liu, C., Fu, Q., Mu, R., Wang, F., Zhou, C., Zhang, L., Yu, B., Zhang, Y., Fang, T., & Tian, F. (2018). Dexmedetomidine alleviates cerebral ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress dependent apoptosis through the PERK-CHOP-Caspase-11 pathway. Brain Research, 1701, 246-254. https://doi.org/10.1016/j.brainres.2018.09.007
Liu C, et al. Dexmedetomidine Alleviates Cerebral Ischemia-reperfusion Injury By Inhibiting Endoplasmic Reticulum Stress Dependent Apoptosis Through the PERK-CHOP-Caspase-11 Pathway. Brain Res. 2018 12 15;1701:246-254. PubMed PMID: 30201260.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dexmedetomidine alleviates cerebral ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress dependent apoptosis through the PERK-CHOP-Caspase-11 pathway. AU - Liu,Chong, AU - Fu,Qiang, AU - Mu,Rong, AU - Wang,Fang, AU - Zhou,Chunjing, AU - Zhang,Li, AU - Yu,Baojin, AU - Zhang,Yang, AU - Fang,Tao, AU - Tian,Fengshi, Y1 - 2018/09/07/ PY - 2018/04/23/received PY - 2018/08/14/revised PY - 2018/09/06/accepted PY - 2018/9/12/pubmed PY - 2019/11/5/medline PY - 2018/9/12/entrez KW - Apoptosis KW - Cerebral ischaemia-reperfusion injury KW - Dexmedetomidine KW - Endoplasmic reticulum stress KW - Neuroprotective SP - 246 EP - 254 JF - Brain research JO - Brain Res VL - 1701 N2 - Dexmedetomidine (Dex) has the neuroprotective effect on cerebral ischemia-reperfusion injury (CIRI). But the mechanism is not yet clear. In this study, we established a model of middle cerebral artery occlusion (MCAO) and treated primary cortical neurons with oxygen glucose deprivation (OGD), followed by Dex treatment. Neurological protection of Dex was then assessed by neurological deficit score, brain edema, TTC staining, TUNEL assay, Western blot analysis, immunohistochemistry, and RT-PCR. The results showed that Dex significantly reduced the neurological deficit score, brain edema and cerebral infarction area due to CIRI. After Dex treatment, the expression levels of ER stress-related apoptosis pathway proteins (GRP78, p-PERK, CHOP and Cleaved-caspase-3) were significantly decreased and the apoptosis of brain cells was also significantly reduced. Immunohistochemistry showed that expression and nuclear localization of CHOP decreased significantly after the application of Dex. The downstream apoptotic protein caspase-11 mediated by PERK-CHOP was also markedly inhibited by Dex. In conclusion, our results suggested that Dex reduced ER stress-induced apoptosis after CIRI. Its protective mechanism may be related to PERK-CHOP-Caspase-11 dependent signaling pathway. SN - 1872-6240 UR - https://www.unboundmedicine.com/medline/citation/30201260/Dexmedetomidine_alleviates_cerebral_ischemia_reperfusion_injury_by_inhibiting_endoplasmic_reticulum_stress_dependent_apoptosis_through_the_PERK_CHOP_Caspase_11_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(18)30464-5 DB - PRIME DP - Unbound Medicine ER -