Idebenone Orchestrates Anti-Inflammatory and Antioxidant Responses to Alleviate Brain Injury After Intracerebral Hemorrhage in Mice
Background: Intracerebral hemorrhage (ICH) is a critical form of stroke with limited treatment options, with secondary brain injury significantly affecting patient outcomes. This study investigated the neuroprotective benefits of idebenone (IDE) in ICH....
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IMR Press
2025-06-01
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| Series: | Journal of Integrative Neuroscience |
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| Online Access: | https://www.imrpress.com/journal/JIN/24/6/10.31083/JIN37182 |
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| author | Chen Chen Liang Cao Mengzhou Xue Ning Zhu |
| author_facet | Chen Chen Liang Cao Mengzhou Xue Ning Zhu |
| author_sort | Chen Chen |
| collection | DOAJ |
| description | Background: Intracerebral hemorrhage (ICH) is a critical form of stroke with limited treatment options, with secondary brain injury significantly affecting patient outcomes. This study investigated the neuroprotective benefits of idebenone (IDE) in ICH. Methods: An ICH model was established in mice and the temporal progression of oxidative stress and neuroinflammation was evaluated. IDE was then administered intraperitoneally for 3 consecutive days to evaluate its therapeutic effects. Tissue histology was examined after staining with hematoxylin-eosin and TdT-mediated dUTP nick end labeling (TUNEL), while oxidative stress was assessed by western blotting and measurement of malondialdehyde (MDA) levels and neuroinflammation was examined using immunostaining, western blotting, and enzyme-linked immunosorbent assay (ELISA). Results: Oxidative stress and neuroinflammation peaked at 3 days post-ICH, with elevated levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and significant microglial activation. IDE-treated mice had reduced hematoma volumes and improved neurological outcomes. IDE administration decreased Kelch-like ECH-associated protein 1 (Keap1) expression while increasing Nrf2 and NAD(P)H quinone oxidoreductase 1 (NQO1) levels, leading to reduced oxidative damage (p < 0.01, p < 0.05, and p < 0.05, respectively). Moreover, IDE attenuated microglial activation and neutrophil recruitment (p < 0.01, p < 0.01), reduced the levels of matrix metalloproteinase-9 (MMP-9), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) levels (p < 0.05, p < 0.05, and p < 0.05, respectively), and increased IL-10 expression (p < 0.01). IDE also preserved the integrity of the blood-brain barrier (BBB) and reduced brain edema. Conclusions: The results demonstrated that IDE exerts neuroprotective effects in ICH through the mitigation of oxidative stress and neuroinflammation during the acute injury phase. IDE may be a viable therapeutic intervention for ICH. |
| format | Article |
| id | doaj-art-9dcf9f7aea9c45e1845b16cab8731593 |
| institution | Kabale University |
| issn | 0219-6352 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | IMR Press |
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| series | Journal of Integrative Neuroscience |
| spelling | doaj-art-9dcf9f7aea9c45e1845b16cab87315932025-08-20T03:33:15ZengIMR PressJournal of Integrative Neuroscience0219-63522025-06-012463718210.31083/JIN37182S0219-6352(25)00950-7Idebenone Orchestrates Anti-Inflammatory and Antioxidant Responses to Alleviate Brain Injury After Intracerebral Hemorrhage in MiceChen Chen0Liang Cao1Mengzhou Xue2Ning Zhu3Department of Neurological Rehabilitation, The Second Affiliated Hospital of Zhengzhou University, 450000 Zhengzhou, Henan, ChinaDepartment of Neurological Rehabilitation, The Second Affiliated Hospital of Zhengzhou University, 450000 Zhengzhou, Henan, ChinaDepartment of Neurological Rehabilitation, The Second Affiliated Hospital of Zhengzhou University, 450000 Zhengzhou, Henan, ChinaDepartment of Neurological Rehabilitation, The Second Affiliated Hospital of Zhengzhou University, 450000 Zhengzhou, Henan, ChinaBackground: Intracerebral hemorrhage (ICH) is a critical form of stroke with limited treatment options, with secondary brain injury significantly affecting patient outcomes. This study investigated the neuroprotective benefits of idebenone (IDE) in ICH. Methods: An ICH model was established in mice and the temporal progression of oxidative stress and neuroinflammation was evaluated. IDE was then administered intraperitoneally for 3 consecutive days to evaluate its therapeutic effects. Tissue histology was examined after staining with hematoxylin-eosin and TdT-mediated dUTP nick end labeling (TUNEL), while oxidative stress was assessed by western blotting and measurement of malondialdehyde (MDA) levels and neuroinflammation was examined using immunostaining, western blotting, and enzyme-linked immunosorbent assay (ELISA). Results: Oxidative stress and neuroinflammation peaked at 3 days post-ICH, with elevated levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and significant microglial activation. IDE-treated mice had reduced hematoma volumes and improved neurological outcomes. IDE administration decreased Kelch-like ECH-associated protein 1 (Keap1) expression while increasing Nrf2 and NAD(P)H quinone oxidoreductase 1 (NQO1) levels, leading to reduced oxidative damage (p < 0.01, p < 0.05, and p < 0.05, respectively). Moreover, IDE attenuated microglial activation and neutrophil recruitment (p < 0.01, p < 0.01), reduced the levels of matrix metalloproteinase-9 (MMP-9), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) levels (p < 0.05, p < 0.05, and p < 0.05, respectively), and increased IL-10 expression (p < 0.01). IDE also preserved the integrity of the blood-brain barrier (BBB) and reduced brain edema. Conclusions: The results demonstrated that IDE exerts neuroprotective effects in ICH through the mitigation of oxidative stress and neuroinflammation during the acute injury phase. IDE may be a viable therapeutic intervention for ICH.https://www.imrpress.com/journal/JIN/24/6/10.31083/JIN37182idebenoneintracerebral hemorrhageneuroprotective agentsoxidative stressinflammation |
| spellingShingle | Chen Chen Liang Cao Mengzhou Xue Ning Zhu Idebenone Orchestrates Anti-Inflammatory and Antioxidant Responses to Alleviate Brain Injury After Intracerebral Hemorrhage in Mice Journal of Integrative Neuroscience idebenone intracerebral hemorrhage neuroprotective agents oxidative stress inflammation |
| title | Idebenone Orchestrates Anti-Inflammatory and Antioxidant Responses to Alleviate Brain Injury After Intracerebral Hemorrhage in Mice |
| title_full | Idebenone Orchestrates Anti-Inflammatory and Antioxidant Responses to Alleviate Brain Injury After Intracerebral Hemorrhage in Mice |
| title_fullStr | Idebenone Orchestrates Anti-Inflammatory and Antioxidant Responses to Alleviate Brain Injury After Intracerebral Hemorrhage in Mice |
| title_full_unstemmed | Idebenone Orchestrates Anti-Inflammatory and Antioxidant Responses to Alleviate Brain Injury After Intracerebral Hemorrhage in Mice |
| title_short | Idebenone Orchestrates Anti-Inflammatory and Antioxidant Responses to Alleviate Brain Injury After Intracerebral Hemorrhage in Mice |
| title_sort | idebenone orchestrates anti inflammatory and antioxidant responses to alleviate brain injury after intracerebral hemorrhage in mice |
| topic | idebenone intracerebral hemorrhage neuroprotective agents oxidative stress inflammation |
| url | https://www.imrpress.com/journal/JIN/24/6/10.31083/JIN37182 |
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