Losmapimod Protected Epileptic Rats From Hippocampal Neuron Damage Through Inhibition of the MAPK Pathway
Objective: This research aimed to validate the therapeutic effect of losmapimod and explore the underlying mechanism in its treatment of epilepsy.Methods: A rat model of epilepsy was constructed with an injection of pilocarpine. Microarray analysis was performed to screen aberrantly expressed mRNAs...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2019.00625/full |
| _version_ | 1818308836468981760 |
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| author | Min Li Lexiang Cui Xuemin Feng Chao Wang Yinmeng Zhang Lijie Wang Ying Ding Teng Zhao |
| author_facet | Min Li Lexiang Cui Xuemin Feng Chao Wang Yinmeng Zhang Lijie Wang Ying Ding Teng Zhao |
| author_sort | Min Li |
| collection | DOAJ |
| description | Objective: This research aimed to validate the therapeutic effect of losmapimod and explore the underlying mechanism in its treatment of epilepsy.Methods: A rat model of epilepsy was constructed with an injection of pilocarpine. Microarray analysis was performed to screen aberrantly expressed mRNAs and activated signaling pathways between epileptic rats and normal controls. A TdT-mediated dUTP nick-end labeling (TUNEL) assay was used to identify cell apoptosis. Hippocampal cytoarchitecture was visualized with Nissl staining. The secretion of inflammatory factors as well as the marker proteins in the mitogen-activated protein kinase (MAPK) pathway were detected by Western blot. A Morris water maze navigation test evaluated the rats’ cognitive functions.Results: Activation of the MAPK signaling pathway was observed in epilepsy rats. A decrease in the MAPK phosphorylation level by application of losmapimod protected against epilepsy by reducing neuron loss. Losmapimod effectively improved memory, reduced the frequency of seizures, protected the neuron from damage, and limited the apoptosis of neurons in epilepsy rats.Conclusion: The application of losmapimod could partly reverse the development of epilepsy. |
| first_indexed | 2024-12-13T07:20:36Z |
| format | Article |
| id | doaj.art-d5322289f3ea47429035e38228f48d8f |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-13T07:20:36Z |
| publishDate | 2019-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-d5322289f3ea47429035e38228f48d8f2022-12-21T23:55:26ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-06-011010.3389/fphar.2019.00625443801Losmapimod Protected Epileptic Rats From Hippocampal Neuron Damage Through Inhibition of the MAPK PathwayMin Li0Lexiang Cui1Xuemin Feng2Chao Wang3Yinmeng Zhang4Lijie Wang5Ying Ding6Teng Zhao7Department of Neurology, The First Hospital of Jilin University, Changchun, ChinaDepartment of Neurology, The First Hospital of Jilin University, Changchun, ChinaDepartment of Neurology, The First Hospital of Jilin University, Changchun, ChinaDepartment of Neurology, The First Hospital of Jilin University, Changchun, ChinaMajor in Clinical Medicine, Medical College of Nanchang University, Nanchang, ChinaDepartment of Traditional Chinese Medicine, General Hospital of FAW, Fourth Hospital of Jilin University, Changchuan, ChinaDepartment of Radiology, The First Hospital of Jilin University, Changchun, ChinaDepartment of Neurology, The First Hospital of Jilin University, Changchun, ChinaObjective: This research aimed to validate the therapeutic effect of losmapimod and explore the underlying mechanism in its treatment of epilepsy.Methods: A rat model of epilepsy was constructed with an injection of pilocarpine. Microarray analysis was performed to screen aberrantly expressed mRNAs and activated signaling pathways between epileptic rats and normal controls. A TdT-mediated dUTP nick-end labeling (TUNEL) assay was used to identify cell apoptosis. Hippocampal cytoarchitecture was visualized with Nissl staining. The secretion of inflammatory factors as well as the marker proteins in the mitogen-activated protein kinase (MAPK) pathway were detected by Western blot. A Morris water maze navigation test evaluated the rats’ cognitive functions.Results: Activation of the MAPK signaling pathway was observed in epilepsy rats. A decrease in the MAPK phosphorylation level by application of losmapimod protected against epilepsy by reducing neuron loss. Losmapimod effectively improved memory, reduced the frequency of seizures, protected the neuron from damage, and limited the apoptosis of neurons in epilepsy rats.Conclusion: The application of losmapimod could partly reverse the development of epilepsy.https://www.frontiersin.org/article/10.3389/fphar.2019.00625/fulllosmapimodmitogen-activated protein kinaseepilepsyhippocampuspilocarpine |
| spellingShingle | Min Li Lexiang Cui Xuemin Feng Chao Wang Yinmeng Zhang Lijie Wang Ying Ding Teng Zhao Losmapimod Protected Epileptic Rats From Hippocampal Neuron Damage Through Inhibition of the MAPK Pathway Frontiers in Pharmacology losmapimod mitogen-activated protein kinase epilepsy hippocampus pilocarpine |
| title | Losmapimod Protected Epileptic Rats From Hippocampal Neuron Damage Through Inhibition of the MAPK Pathway |
| title_full | Losmapimod Protected Epileptic Rats From Hippocampal Neuron Damage Through Inhibition of the MAPK Pathway |
| title_fullStr | Losmapimod Protected Epileptic Rats From Hippocampal Neuron Damage Through Inhibition of the MAPK Pathway |
| title_full_unstemmed | Losmapimod Protected Epileptic Rats From Hippocampal Neuron Damage Through Inhibition of the MAPK Pathway |
| title_short | Losmapimod Protected Epileptic Rats From Hippocampal Neuron Damage Through Inhibition of the MAPK Pathway |
| title_sort | losmapimod protected epileptic rats from hippocampal neuron damage through inhibition of the mapk pathway |
| topic | losmapimod mitogen-activated protein kinase epilepsy hippocampus pilocarpine |
| url | https://www.frontiersin.org/article/10.3389/fphar.2019.00625/full |
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