Neuroprotection by Nrf2 via modulating microglial phenotype and phagocytosis after intracerebral hemorrhage
Activated microglia are divided into pro-inflammatory and anti-inflammatory functional states. In anti-inflammatory state, activated microglia contribute to phagocytosis, neural repair and anti-inflammation. Nrf2 as a major endogenous regulator in hematoma clearance after intracerebral hemorrhage (I...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-02-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023009842 |
| _version_ | 1811161669054758912 |
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| author | Chuntian Liang Lirong Liu Shuangjin Bao Zhenjia Yao Qinqin Bai Pengcheng Fu Xiangyu Liu John H. Zhang Gaiqing Wang |
| author_facet | Chuntian Liang Lirong Liu Shuangjin Bao Zhenjia Yao Qinqin Bai Pengcheng Fu Xiangyu Liu John H. Zhang Gaiqing Wang |
| author_sort | Chuntian Liang |
| collection | DOAJ |
| description | Activated microglia are divided into pro-inflammatory and anti-inflammatory functional states. In anti-inflammatory state, activated microglia contribute to phagocytosis, neural repair and anti-inflammation. Nrf2 as a major endogenous regulator in hematoma clearance after intracerebral hemorrhage (ICH) has received much attention. This study aims to investigate the mechanism underlying Nrf2-mediated regulation of microglial phenotype and phagocytosis in hematoma clearance after ICH. In vitro experiments, BV-2 cells were assigned to normal group and administration group (Nrf2-siRNA, Nrf2 agonists Monascin and Xuezhikang). In vivo experiments, mice were divided into 5 groups: sham, ICH + vehicle, ICH + Nrf2−/−, ICH + Monascin and ICH + Xuezhikang. In vitro and in vivo, 72 h after administration of Monascin and Xuezhikang, the expression of Nrf2, inflammatory-associated factors such as Trem1, TNF-α and CD80, anti-inflammatory, neural repair and phagocytic associated factors such as Trem2, CD206 and BDNF were analyzed by the Western blot method. In vitro, fluorescent latex beads or erythrocytes were uptaken by BV-2 cells in order to study microglial phagocytic ability. In vivo, hemoglobin levels reflect the hematoma volume. In this study, Nrf2 agonists (Monascin and Xuezhikang) upregulated the expression of Trem2, CD206 and BDNF while decreased the expression of Trem1, TNF-α and CD80 both in vivo and in vitro. At the same time, after Monascin and Xuezhikang treatment, the phagocytic capacity of microglia increased in vitro, neurological deficits improved and hematoma volume lessened in vivo. These results were reversed in the Nrf2-siRNA or the Nrf2−/− mice. All these results indicated that Nrf2 enhanced hematoma clearance and neural repair, improved neurological outcomes through enhancing microglial phagocytosis and alleviating neuroinflammation. |
| first_indexed | 2024-04-10T06:18:03Z |
| format | Article |
| id | doaj.art-0ed3def5d2c343e3adfa1c66c681d479 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-10T06:18:03Z |
| publishDate | 2023-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-0ed3def5d2c343e3adfa1c66c681d4792023-03-02T05:02:42ZengElsevierHeliyon2405-84402023-02-0192e13777Neuroprotection by Nrf2 via modulating microglial phenotype and phagocytosis after intracerebral hemorrhageChuntian Liang0Lirong Liu1Shuangjin Bao2Zhenjia Yao3Qinqin Bai4Pengcheng Fu5Xiangyu Liu6John H. Zhang7Gaiqing Wang8Department of Neurology, Shanxi Medical University, Taiyuan 030000, ChinaDepartment of Neurology, Shanxi Medical University, Taiyuan 030000, China; People's Hospital of Yaodu District, Linfen 041000, ChinaDepartment of Pathology and Pathophysiology, Basic Medical College, Shanxi Medical University, Taiyuan 030000, ChinaDepartment of Neurology, Shanxi Medical University, Taiyuan 030000, ChinaDepartment of Neurology, Shanxi Medical University, Taiyuan 030000, ChinaDepartment of Neurology, Shenzhen Longhua District Central Hospital, Shenzhen 518000, ChinaDepartment of Neurology, Shenzhen Longhua District Central Hospital, Shenzhen 518000, ChinaDepartment of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA, USA; Department of Anesthesiology, Loma Linda University School of Medicine, Loma Linda, CA, USADepartment of Neurology, Shanxi Medical University, Taiyuan 030000, China; Department of Neurology, Sanya Central Hospital (Haian Third People's Hospital), Hainan Medical University, Sanya 572000, China; Corresponding author. Department of Neurology, Sanya Central Hospital (Haian Third People's Hospital), Hainan Medical University, Sanya 572000, ChinaActivated microglia are divided into pro-inflammatory and anti-inflammatory functional states. In anti-inflammatory state, activated microglia contribute to phagocytosis, neural repair and anti-inflammation. Nrf2 as a major endogenous regulator in hematoma clearance after intracerebral hemorrhage (ICH) has received much attention. This study aims to investigate the mechanism underlying Nrf2-mediated regulation of microglial phenotype and phagocytosis in hematoma clearance after ICH. In vitro experiments, BV-2 cells were assigned to normal group and administration group (Nrf2-siRNA, Nrf2 agonists Monascin and Xuezhikang). In vivo experiments, mice were divided into 5 groups: sham, ICH + vehicle, ICH + Nrf2−/−, ICH + Monascin and ICH + Xuezhikang. In vitro and in vivo, 72 h after administration of Monascin and Xuezhikang, the expression of Nrf2, inflammatory-associated factors such as Trem1, TNF-α and CD80, anti-inflammatory, neural repair and phagocytic associated factors such as Trem2, CD206 and BDNF were analyzed by the Western blot method. In vitro, fluorescent latex beads or erythrocytes were uptaken by BV-2 cells in order to study microglial phagocytic ability. In vivo, hemoglobin levels reflect the hematoma volume. In this study, Nrf2 agonists (Monascin and Xuezhikang) upregulated the expression of Trem2, CD206 and BDNF while decreased the expression of Trem1, TNF-α and CD80 both in vivo and in vitro. At the same time, after Monascin and Xuezhikang treatment, the phagocytic capacity of microglia increased in vitro, neurological deficits improved and hematoma volume lessened in vivo. These results were reversed in the Nrf2-siRNA or the Nrf2−/− mice. All these results indicated that Nrf2 enhanced hematoma clearance and neural repair, improved neurological outcomes through enhancing microglial phagocytosis and alleviating neuroinflammation.http://www.sciencedirect.com/science/article/pii/S2405844023009842Microglial phenotypePhagocytosisNrf2Hematoma clearanceIntracerebral hemorrhage |
| spellingShingle | Chuntian Liang Lirong Liu Shuangjin Bao Zhenjia Yao Qinqin Bai Pengcheng Fu Xiangyu Liu John H. Zhang Gaiqing Wang Neuroprotection by Nrf2 via modulating microglial phenotype and phagocytosis after intracerebral hemorrhage Heliyon Microglial phenotype Phagocytosis Nrf2 Hematoma clearance Intracerebral hemorrhage |
| title | Neuroprotection by Nrf2 via modulating microglial phenotype and phagocytosis after intracerebral hemorrhage |
| title_full | Neuroprotection by Nrf2 via modulating microglial phenotype and phagocytosis after intracerebral hemorrhage |
| title_fullStr | Neuroprotection by Nrf2 via modulating microglial phenotype and phagocytosis after intracerebral hemorrhage |
| title_full_unstemmed | Neuroprotection by Nrf2 via modulating microglial phenotype and phagocytosis after intracerebral hemorrhage |
| title_short | Neuroprotection by Nrf2 via modulating microglial phenotype and phagocytosis after intracerebral hemorrhage |
| title_sort | neuroprotection by nrf2 via modulating microglial phenotype and phagocytosis after intracerebral hemorrhage |
| topic | Microglial phenotype Phagocytosis Nrf2 Hematoma clearance Intracerebral hemorrhage |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023009842 |
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