Dexmedetomidine Protects Mouse Brain from Ischemia-Reperfusion Injury via Inhibiting Neuronal Autophagy through Up-Regulating HIF-1α
Stroke is the leading cause of death in China and produces a heavy socio-economic burden in the past decades. Previous studies have shown that dexmedetomidine (DEX) is neuroprotective after cerebral ischemia. However, the role of autophagy during DEX-mediated neuroprotection after cerebral ischemia...
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Frontiers Media S.A.
2017-07-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fncel.2017.00197/full |
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| author | Cong Luo Ming-Wen Ouyang Ying-Ying Fang Shu-Ji Li Quan Zhou Jun Fan Zai-Sheng Qin Tao Tao |
| author_facet | Cong Luo Ming-Wen Ouyang Ying-Ying Fang Shu-Ji Li Quan Zhou Jun Fan Zai-Sheng Qin Tao Tao |
| author_sort | Cong Luo |
| collection | DOAJ |
| description | Stroke is the leading cause of death in China and produces a heavy socio-economic burden in the past decades. Previous studies have shown that dexmedetomidine (DEX) is neuroprotective after cerebral ischemia. However, the role of autophagy during DEX-mediated neuroprotection after cerebral ischemia is still unknown. In this study, we found that post-conditioning with DEX and DEX+3-methyladenine (3-MA) (autophagy inhibitor) reduced brain infarct size and improved neurological deficits compared with DEX+RAPA (autophagy inducer) 24 h after transient middle cerebral artery artery occlusion (tMCAO) model in mice. DEX inhibited the neuronal autophagy in the peri-ischemic brain, and increased viability and decreased apoptosis of primary cultured neurons in oxygen-glucose deprivation (OGD) model. DEX induced expression of Bcl-1 and p62, while reduced the expression of microtubule-associated protein 1 light chain 3 (LC3) and Beclin 1 in primary cultured neurons through inhibition of apoptosis and autophagy. Meanwhile, DEX promoted the expression of hypoxia-inducible factor-1α (HIF-1α) both in vivo and in vitro, and 2-Methoxyestradiol (2ME2), an inhibitor of HIF-1α, could reverse DEX-induced autophagic inhibition. In conclusion, our study suggests that post-conditioning with DEX at the beginning of reperfusion protects mouse brain from ischemia-reperfusion injury via inhibition of neuronal autophagy by upregulation of HIF-1α, which provides a potential therapeutic treatment for acute ischemic injury. |
| first_indexed | 2024-12-20T06:19:35Z |
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| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-20T06:19:35Z |
| publishDate | 2017-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-bfdbcd3d68a148228ba1dc6ffe7cbb8a2022-12-21T19:50:27ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022017-07-011110.3389/fncel.2017.00197260320Dexmedetomidine Protects Mouse Brain from Ischemia-Reperfusion Injury via Inhibiting Neuronal Autophagy through Up-Regulating HIF-1αCong Luo0Ming-Wen Ouyang1Ying-Ying Fang2Shu-Ji Li3Quan Zhou4Jun Fan5Zai-Sheng Qin6Tao Tao7Department of Anesthesiology, Nanfang Hospital, Southern Medical UniversityGuangzhou, ChinaDepartment of Anesthesiology, The Fifth Affiliated Hospital, Southern Medical UniversityGuangzhou, ChinaDepartment of Neurobiology, School of Basic Medical Sciences, Southern Medical UniversityGuangzhou, ChinaDepartment of Neurobiology, School of Basic Medical Sciences, Southern Medical UniversityGuangzhou, ChinaDepartment of Anesthesiology, Nanfang Hospital, Southern Medical UniversityGuangzhou, ChinaDepartment of Anesthesiology, Nanfang Hospital, Southern Medical UniversityGuangzhou, ChinaDepartment of Anesthesiology, Nanfang Hospital, Southern Medical UniversityGuangzhou, ChinaDepartment of Anesthesiology, Nanfang Hospital, Southern Medical UniversityGuangzhou, ChinaStroke is the leading cause of death in China and produces a heavy socio-economic burden in the past decades. Previous studies have shown that dexmedetomidine (DEX) is neuroprotective after cerebral ischemia. However, the role of autophagy during DEX-mediated neuroprotection after cerebral ischemia is still unknown. In this study, we found that post-conditioning with DEX and DEX+3-methyladenine (3-MA) (autophagy inhibitor) reduced brain infarct size and improved neurological deficits compared with DEX+RAPA (autophagy inducer) 24 h after transient middle cerebral artery artery occlusion (tMCAO) model in mice. DEX inhibited the neuronal autophagy in the peri-ischemic brain, and increased viability and decreased apoptosis of primary cultured neurons in oxygen-glucose deprivation (OGD) model. DEX induced expression of Bcl-1 and p62, while reduced the expression of microtubule-associated protein 1 light chain 3 (LC3) and Beclin 1 in primary cultured neurons through inhibition of apoptosis and autophagy. Meanwhile, DEX promoted the expression of hypoxia-inducible factor-1α (HIF-1α) both in vivo and in vitro, and 2-Methoxyestradiol (2ME2), an inhibitor of HIF-1α, could reverse DEX-induced autophagic inhibition. In conclusion, our study suggests that post-conditioning with DEX at the beginning of reperfusion protects mouse brain from ischemia-reperfusion injury via inhibition of neuronal autophagy by upregulation of HIF-1α, which provides a potential therapeutic treatment for acute ischemic injury.http://journal.frontiersin.org/article/10.3389/fncel.2017.00197/fulldexmedetomidinecerebral ischemianeuroprotectionautophagyHIF-1α |
| spellingShingle | Cong Luo Ming-Wen Ouyang Ying-Ying Fang Shu-Ji Li Quan Zhou Jun Fan Zai-Sheng Qin Tao Tao Dexmedetomidine Protects Mouse Brain from Ischemia-Reperfusion Injury via Inhibiting Neuronal Autophagy through Up-Regulating HIF-1α Frontiers in Cellular Neuroscience dexmedetomidine cerebral ischemia neuroprotection autophagy HIF-1α |
| title | Dexmedetomidine Protects Mouse Brain from Ischemia-Reperfusion Injury via Inhibiting Neuronal Autophagy through Up-Regulating HIF-1α |
| title_full | Dexmedetomidine Protects Mouse Brain from Ischemia-Reperfusion Injury via Inhibiting Neuronal Autophagy through Up-Regulating HIF-1α |
| title_fullStr | Dexmedetomidine Protects Mouse Brain from Ischemia-Reperfusion Injury via Inhibiting Neuronal Autophagy through Up-Regulating HIF-1α |
| title_full_unstemmed | Dexmedetomidine Protects Mouse Brain from Ischemia-Reperfusion Injury via Inhibiting Neuronal Autophagy through Up-Regulating HIF-1α |
| title_short | Dexmedetomidine Protects Mouse Brain from Ischemia-Reperfusion Injury via Inhibiting Neuronal Autophagy through Up-Regulating HIF-1α |
| title_sort | dexmedetomidine protects mouse brain from ischemia reperfusion injury via inhibiting neuronal autophagy through up regulating hif 1α |
| topic | dexmedetomidine cerebral ischemia neuroprotection autophagy HIF-1α |
| url | http://journal.frontiersin.org/article/10.3389/fncel.2017.00197/full |
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