Pterostilbene attenuates microglial inflammation and brain injury after intracerebral hemorrhage in an OPA1-dependent manner
Microglial activation and subsequent inflammatory responses are critical processes in aggravating secondary brain injury after intracerebral hemorrhage (ICH). Pterostilbene (3’, 5’-dimethoxy-resveratrol) features antioxidant and anti-inflammation properties and has been proven neuroprotective. In th...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1172334/full |
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| author | Yang Wu Qing Hu Xiaoliang Wang Hongbo Cheng Jiegang Yu Yang Li Jianing Luo Qingjiu Zhang Jianliang Wu Gengshen Zhang |
| author_facet | Yang Wu Qing Hu Xiaoliang Wang Hongbo Cheng Jiegang Yu Yang Li Jianing Luo Qingjiu Zhang Jianliang Wu Gengshen Zhang |
| author_sort | Yang Wu |
| collection | DOAJ |
| description | Microglial activation and subsequent inflammatory responses are critical processes in aggravating secondary brain injury after intracerebral hemorrhage (ICH). Pterostilbene (3’, 5’-dimethoxy-resveratrol) features antioxidant and anti-inflammation properties and has been proven neuroprotective. In this study, we aimed to explore whether Pterostilbene could attenuate neuroinflammation after experimental ICH, as well as underlying molecular mechanisms. Here, a collagenase-induced ICH in mice was followed by intraperitoneal injection of Pterostilbene (10 mg/kg) or vehicle once daily. PTE-treated mice performed significantly better than vehicle-treated controls in the neurological behavior test after ICH. Furthermore, our results showed that Pterostilbene reduced lesion volume and neural apoptosis, and alleviated blood-brain barrier (BBB) damage and brain edema. RNA sequencing and subsequent experiments showed that ICH-induced neuroinflammation and microglial proinflammatory activities were markedly suppressed by Pterostilbene treatment. With regard to the mechanisms, we identified that the anti-inflammatory effects of Pterostilbene relied on remodeling mitochondrial dynamics in microglia. Concretely, Pterostilbene reversed the downregulation of OPA1, promoted mitochondrial fusion, restored normal mitochondrial morphology, and reduced mitochondrial fragmentation and superoxide in microglia after OxyHb treatment. Moreover, conditionally deleting microglial OPA1 in mice largely countered the effects of Pterostilbene on alleviating microglial inflammation, BBB damage, brain edema and neurological impairment following ICH. In summary, we provided the first evidence that Pterostilbene is a promising agent for alleviating neuroinflammation and brain injury after ICH in mice, and uncovered a novel regulatory relationship between Pterostilbene and OPA1-mediated mitochondrial fusion. |
| first_indexed | 2024-03-12T16:54:29Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-12T16:54:29Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-42a246f630d04e67ad279fd2edfd0bc02023-08-08T09:28:36ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-08-011410.3389/fimmu.2023.11723341172334Pterostilbene attenuates microglial inflammation and brain injury after intracerebral hemorrhage in an OPA1-dependent mannerYang Wu0Qing Hu1Xiaoliang Wang2Hongbo Cheng3Jiegang Yu4Yang Li5Jianing Luo6Qingjiu Zhang7Jianliang Wu8Gengshen Zhang9Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Neurosurgery, Tangdu Hospital, Air Force Medical University, Xi’an, Shaanxi, ChinaDepartment of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Neurosurgery, The General Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Neurosurgery, West Theater General Hospital, Chengdu, Sichuan, ChinaDepartment of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaMicroglial activation and subsequent inflammatory responses are critical processes in aggravating secondary brain injury after intracerebral hemorrhage (ICH). Pterostilbene (3’, 5’-dimethoxy-resveratrol) features antioxidant and anti-inflammation properties and has been proven neuroprotective. In this study, we aimed to explore whether Pterostilbene could attenuate neuroinflammation after experimental ICH, as well as underlying molecular mechanisms. Here, a collagenase-induced ICH in mice was followed by intraperitoneal injection of Pterostilbene (10 mg/kg) or vehicle once daily. PTE-treated mice performed significantly better than vehicle-treated controls in the neurological behavior test after ICH. Furthermore, our results showed that Pterostilbene reduced lesion volume and neural apoptosis, and alleviated blood-brain barrier (BBB) damage and brain edema. RNA sequencing and subsequent experiments showed that ICH-induced neuroinflammation and microglial proinflammatory activities were markedly suppressed by Pterostilbene treatment. With regard to the mechanisms, we identified that the anti-inflammatory effects of Pterostilbene relied on remodeling mitochondrial dynamics in microglia. Concretely, Pterostilbene reversed the downregulation of OPA1, promoted mitochondrial fusion, restored normal mitochondrial morphology, and reduced mitochondrial fragmentation and superoxide in microglia after OxyHb treatment. Moreover, conditionally deleting microglial OPA1 in mice largely countered the effects of Pterostilbene on alleviating microglial inflammation, BBB damage, brain edema and neurological impairment following ICH. In summary, we provided the first evidence that Pterostilbene is a promising agent for alleviating neuroinflammation and brain injury after ICH in mice, and uncovered a novel regulatory relationship between Pterostilbene and OPA1-mediated mitochondrial fusion.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1172334/fullintracerebral hemorrhagepterostilbeneneuroinflammationmicrogliamitochondriaOPA1 |
| spellingShingle | Yang Wu Qing Hu Xiaoliang Wang Hongbo Cheng Jiegang Yu Yang Li Jianing Luo Qingjiu Zhang Jianliang Wu Gengshen Zhang Pterostilbene attenuates microglial inflammation and brain injury after intracerebral hemorrhage in an OPA1-dependent manner Frontiers in Immunology intracerebral hemorrhage pterostilbene neuroinflammation microglia mitochondria OPA1 |
| title | Pterostilbene attenuates microglial inflammation and brain injury after intracerebral hemorrhage in an OPA1-dependent manner |
| title_full | Pterostilbene attenuates microglial inflammation and brain injury after intracerebral hemorrhage in an OPA1-dependent manner |
| title_fullStr | Pterostilbene attenuates microglial inflammation and brain injury after intracerebral hemorrhage in an OPA1-dependent manner |
| title_full_unstemmed | Pterostilbene attenuates microglial inflammation and brain injury after intracerebral hemorrhage in an OPA1-dependent manner |
| title_short | Pterostilbene attenuates microglial inflammation and brain injury after intracerebral hemorrhage in an OPA1-dependent manner |
| title_sort | pterostilbene attenuates microglial inflammation and brain injury after intracerebral hemorrhage in an opa1 dependent manner |
| topic | intracerebral hemorrhage pterostilbene neuroinflammation microglia mitochondria OPA1 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1172334/full |
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