Anticonvulsant Effect of Carbenoxolone on Chronic Epileptic Rats and Its Mechanism Related to Connexin and High-Frequency Oscillations
ObjectiveThis study was designed to investigate the influence and mechanism of gap junction carbenoxolone (CBX) on dynamic changes in the spectral power of ripples and fast ripples (FRs) in the hippocampus of chronic epileptic rats.MethodsThe lithium-pilocarpine (PILO) status epilepticus (SE) model...
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2022.870947/full |
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| author | Benke Liu Benke Liu Benke Liu Xiao Ran Xiao Ran Yanjun Yi Yanjun Yi Xinyu Zhang Xinyu Zhang Hengsheng Chen Hengsheng Chen Yue Hu Yue Hu |
| author_facet | Benke Liu Benke Liu Benke Liu Xiao Ran Xiao Ran Yanjun Yi Yanjun Yi Xinyu Zhang Xinyu Zhang Hengsheng Chen Hengsheng Chen Yue Hu Yue Hu |
| author_sort | Benke Liu |
| collection | DOAJ |
| description | ObjectiveThis study was designed to investigate the influence and mechanism of gap junction carbenoxolone (CBX) on dynamic changes in the spectral power of ripples and fast ripples (FRs) in the hippocampus of chronic epileptic rats.MethodsThe lithium-pilocarpine (PILO) status epilepticus (SE) model (PILO group) and the CBX pretreatment model (CBX + PILO group) were established to analyze dynamic changes in the spectral power of ripples and FRs, and the dynamic expression of connexin (CX)26, CX32, CX36, and CX43 in the hippocampus of chronic epileptic rats.ResultsWithin 28 days after SE, the number of spontaneous recurrent seizures (SRSs) in the PILO group was significantly higher than that in the CBX + PILO group. The average spectral power of FRs in the PILO group was significantly higher than the baseline level at 1 and 7 days after SE. The average spectral power of FRs in the PILO group was significantly higher than that in the CBX + PILO group at 1, 7, and 14 days after SE. Seizures induced an increase in CX43 expression at 1 and 7 days after SE, but had no significant effect on CX26, CX36, or CX32. CBX pretreatment did not affect the expression of CXs in the hippocampus of normal rats, but it inhibited the expression of CX43 in epileptic rats. The number of SRSs at 2 and 4 weeks after SE had the highest correlation with the average spectral power of FRs; the average spectral power of FRs was moderately correlated with the expression of CX43.ConclusionThe results of this study indicate that the energy of FRs may be regulated by its interference with the expression of CX43, and thus, affect seizures. Blocking the expression of CX43 thereby reduces the formation of pathological high-frequency oscillations (HFOs), making it a promising strategy for the treatment of chronic epilepsy. |
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| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-12T21:11:59Z |
| publishDate | 2022-05-01 |
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| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-3b672e7f7e1f439ea97658bc954618d52022-12-22T00:11:52ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992022-05-011510.3389/fnmol.2022.870947870947Anticonvulsant Effect of Carbenoxolone on Chronic Epileptic Rats and Its Mechanism Related to Connexin and High-Frequency OscillationsBenke Liu0Benke Liu1Benke Liu2Xiao Ran3Xiao Ran4Yanjun Yi5Yanjun Yi6Xinyu Zhang7Xinyu Zhang8Hengsheng Chen9Hengsheng Chen10Yue Hu11Yue Hu12Department of Neurology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaMinistry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, ChinaShenzhen Baoan Women’s and Children’s Hospital, Jinan University, Shenzhen, ChinaDepartment of Neurology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaMinistry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, ChinaDepartment of Neurology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaMinistry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, ChinaDepartment of Neurology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaMinistry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, ChinaDepartment of Neurology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaMinistry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, ChinaDepartment of Neurology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaMinistry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, ChinaObjectiveThis study was designed to investigate the influence and mechanism of gap junction carbenoxolone (CBX) on dynamic changes in the spectral power of ripples and fast ripples (FRs) in the hippocampus of chronic epileptic rats.MethodsThe lithium-pilocarpine (PILO) status epilepticus (SE) model (PILO group) and the CBX pretreatment model (CBX + PILO group) were established to analyze dynamic changes in the spectral power of ripples and FRs, and the dynamic expression of connexin (CX)26, CX32, CX36, and CX43 in the hippocampus of chronic epileptic rats.ResultsWithin 28 days after SE, the number of spontaneous recurrent seizures (SRSs) in the PILO group was significantly higher than that in the CBX + PILO group. The average spectral power of FRs in the PILO group was significantly higher than the baseline level at 1 and 7 days after SE. The average spectral power of FRs in the PILO group was significantly higher than that in the CBX + PILO group at 1, 7, and 14 days after SE. Seizures induced an increase in CX43 expression at 1 and 7 days after SE, but had no significant effect on CX26, CX36, or CX32. CBX pretreatment did not affect the expression of CXs in the hippocampus of normal rats, but it inhibited the expression of CX43 in epileptic rats. The number of SRSs at 2 and 4 weeks after SE had the highest correlation with the average spectral power of FRs; the average spectral power of FRs was moderately correlated with the expression of CX43.ConclusionThe results of this study indicate that the energy of FRs may be regulated by its interference with the expression of CX43, and thus, affect seizures. Blocking the expression of CX43 thereby reduces the formation of pathological high-frequency oscillations (HFOs), making it a promising strategy for the treatment of chronic epilepsy.https://www.frontiersin.org/articles/10.3389/fnmol.2022.870947/fullcarbenoxolonechronic epilepsyconnexinripplesfast ripples |
| spellingShingle | Benke Liu Benke Liu Benke Liu Xiao Ran Xiao Ran Yanjun Yi Yanjun Yi Xinyu Zhang Xinyu Zhang Hengsheng Chen Hengsheng Chen Yue Hu Yue Hu Anticonvulsant Effect of Carbenoxolone on Chronic Epileptic Rats and Its Mechanism Related to Connexin and High-Frequency Oscillations Frontiers in Molecular Neuroscience carbenoxolone chronic epilepsy connexin ripples fast ripples |
| title | Anticonvulsant Effect of Carbenoxolone on Chronic Epileptic Rats and Its Mechanism Related to Connexin and High-Frequency Oscillations |
| title_full | Anticonvulsant Effect of Carbenoxolone on Chronic Epileptic Rats and Its Mechanism Related to Connexin and High-Frequency Oscillations |
| title_fullStr | Anticonvulsant Effect of Carbenoxolone on Chronic Epileptic Rats and Its Mechanism Related to Connexin and High-Frequency Oscillations |
| title_full_unstemmed | Anticonvulsant Effect of Carbenoxolone on Chronic Epileptic Rats and Its Mechanism Related to Connexin and High-Frequency Oscillations |
| title_short | Anticonvulsant Effect of Carbenoxolone on Chronic Epileptic Rats and Its Mechanism Related to Connexin and High-Frequency Oscillations |
| title_sort | anticonvulsant effect of carbenoxolone on chronic epileptic rats and its mechanism related to connexin and high frequency oscillations |
| topic | carbenoxolone chronic epilepsy connexin ripples fast ripples |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2022.870947/full |
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