Sodium Benzoate Attenuates Secondary Brain Injury by Inhibiting Neuronal Apoptosis and Reducing Mitochondria-Mediated Oxidative Stress in a Rat Model of Intracerebral Hemorrhage: Possible Involvement of DJ-1/Akt/IKK/NFκB Pathway
Intracerebral hemorrhage (ICH) is a devastating disease with high rates of mortality and morbidity. The aim of this study was to explore whether Sodium Benzoate (NaB) could reduce neural cell apoptosis and alleviate neurological deficits after ICH. To assess the therapeutic effects of NaB, first, we...
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Frontiers Media S.A.
2019-04-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnmol.2019.00105/full |
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| author | Weilin Xu Tao Li Liansheng Gao Cameron Lenahan Jingwei Zheng Jun Yan Anwen Shao Jianmin Zhang Jianmin Zhang Jianmin Zhang |
| author_facet | Weilin Xu Tao Li Liansheng Gao Cameron Lenahan Jingwei Zheng Jun Yan Anwen Shao Jianmin Zhang Jianmin Zhang Jianmin Zhang |
| author_sort | Weilin Xu |
| collection | DOAJ |
| description | Intracerebral hemorrhage (ICH) is a devastating disease with high rates of mortality and morbidity. The aim of this study was to explore whether Sodium Benzoate (NaB) could reduce neural cell apoptosis and alleviate neurological deficits after ICH. To assess the therapeutic effects of NaB, first, we measured brain water content, neurobehavior, and blood-brain barrier (BBB) integrity at 24 h after ICH in different groups. Then western blot and immunofluorescence staining (IF) were applied to test the levels of different proteins. Transmission electron microscope (TEM) was used to observe ultra-structures within the cells in different groups. The results showed that levels of DJ-1, p-Akt and p-IκB kinase (IKK) increased after ICH and peaked at 24 h. Besides, NaB significantly upregulated DJ-1 in both cytoplasm and mitochondria, and also increased the levels of p-Akt, p-IKK and Bcl-2/Bax ratio, but decreased the levels of caspase-3 and caspase-9. Additionally, NaB decreased reactive oxygen species (ROS) while increased adenosine triphosphate (ATP), which then improving the neurological functions at 24 h and long-term (21 days) memory and spatial learning ability after ICH. However, the results mentioned above could be greatly reversed by MK2206 and rotenone. Therefore, we concluded that NaB could attenuate secondary brain injury via inhibiting neuronal apoptosis and reducing mitochondria-mediated oxidative stress via DJ-1/Akt/IKK/NFκB pathway. |
| first_indexed | 2024-12-19T06:19:19Z |
| format | Article |
| id | doaj.art-6da76b512f5c4cd3b281701760be52a3 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-19T06:19:19Z |
| publishDate | 2019-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-6da76b512f5c4cd3b281701760be52a32022-12-21T20:32:46ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992019-04-011210.3389/fnmol.2019.00105441421Sodium Benzoate Attenuates Secondary Brain Injury by Inhibiting Neuronal Apoptosis and Reducing Mitochondria-Mediated Oxidative Stress in a Rat Model of Intracerebral Hemorrhage: Possible Involvement of DJ-1/Akt/IKK/NFκB PathwayWeilin Xu0Tao Li1Liansheng Gao2Cameron Lenahan3Jingwei Zheng4Jun Yan5Anwen Shao6Jianmin Zhang7Jianmin Zhang8Jianmin Zhang9Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaBurrell College of Osteopathic Medicine, Las Cruces, NM, United StatesDepartment of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Neurosurgery, Affiliated Tumor Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaBrain Research Institute, Zhejiang University, Hangzhou, ChinaCollaborative Innovation Center for Brain Science, Zhejiang University, Hangzhou, ChinaIntracerebral hemorrhage (ICH) is a devastating disease with high rates of mortality and morbidity. The aim of this study was to explore whether Sodium Benzoate (NaB) could reduce neural cell apoptosis and alleviate neurological deficits after ICH. To assess the therapeutic effects of NaB, first, we measured brain water content, neurobehavior, and blood-brain barrier (BBB) integrity at 24 h after ICH in different groups. Then western blot and immunofluorescence staining (IF) were applied to test the levels of different proteins. Transmission electron microscope (TEM) was used to observe ultra-structures within the cells in different groups. The results showed that levels of DJ-1, p-Akt and p-IκB kinase (IKK) increased after ICH and peaked at 24 h. Besides, NaB significantly upregulated DJ-1 in both cytoplasm and mitochondria, and also increased the levels of p-Akt, p-IKK and Bcl-2/Bax ratio, but decreased the levels of caspase-3 and caspase-9. Additionally, NaB decreased reactive oxygen species (ROS) while increased adenosine triphosphate (ATP), which then improving the neurological functions at 24 h and long-term (21 days) memory and spatial learning ability after ICH. However, the results mentioned above could be greatly reversed by MK2206 and rotenone. Therefore, we concluded that NaB could attenuate secondary brain injury via inhibiting neuronal apoptosis and reducing mitochondria-mediated oxidative stress via DJ-1/Akt/IKK/NFκB pathway.https://www.frontiersin.org/article/10.3389/fnmol.2019.00105/fullDJ-1sodium benzoateintracerebral hemorrhagesecondary brain injury neuronal apoptosisoxidative stress |
| spellingShingle | Weilin Xu Tao Li Liansheng Gao Cameron Lenahan Jingwei Zheng Jun Yan Anwen Shao Jianmin Zhang Jianmin Zhang Jianmin Zhang Sodium Benzoate Attenuates Secondary Brain Injury by Inhibiting Neuronal Apoptosis and Reducing Mitochondria-Mediated Oxidative Stress in a Rat Model of Intracerebral Hemorrhage: Possible Involvement of DJ-1/Akt/IKK/NFκB Pathway Frontiers in Molecular Neuroscience DJ-1 sodium benzoate intracerebral hemorrhage secondary brain injury neuronal apoptosis oxidative stress |
| title | Sodium Benzoate Attenuates Secondary Brain Injury by Inhibiting Neuronal Apoptosis and Reducing Mitochondria-Mediated Oxidative Stress in a Rat Model of Intracerebral Hemorrhage: Possible Involvement of DJ-1/Akt/IKK/NFκB Pathway |
| title_full | Sodium Benzoate Attenuates Secondary Brain Injury by Inhibiting Neuronal Apoptosis and Reducing Mitochondria-Mediated Oxidative Stress in a Rat Model of Intracerebral Hemorrhage: Possible Involvement of DJ-1/Akt/IKK/NFκB Pathway |
| title_fullStr | Sodium Benzoate Attenuates Secondary Brain Injury by Inhibiting Neuronal Apoptosis and Reducing Mitochondria-Mediated Oxidative Stress in a Rat Model of Intracerebral Hemorrhage: Possible Involvement of DJ-1/Akt/IKK/NFκB Pathway |
| title_full_unstemmed | Sodium Benzoate Attenuates Secondary Brain Injury by Inhibiting Neuronal Apoptosis and Reducing Mitochondria-Mediated Oxidative Stress in a Rat Model of Intracerebral Hemorrhage: Possible Involvement of DJ-1/Akt/IKK/NFκB Pathway |
| title_short | Sodium Benzoate Attenuates Secondary Brain Injury by Inhibiting Neuronal Apoptosis and Reducing Mitochondria-Mediated Oxidative Stress in a Rat Model of Intracerebral Hemorrhage: Possible Involvement of DJ-1/Akt/IKK/NFκB Pathway |
| title_sort | sodium benzoate attenuates secondary brain injury by inhibiting neuronal apoptosis and reducing mitochondria mediated oxidative stress in a rat model of intracerebral hemorrhage possible involvement of dj 1 akt ikk nfκb pathway |
| topic | DJ-1 sodium benzoate intracerebral hemorrhage secondary brain injury neuronal apoptosis oxidative stress |
| url | https://www.frontiersin.org/article/10.3389/fnmol.2019.00105/full |
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