{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:04:29Z","timestamp":1791345869558,"version":"4.3.1"},"reference-count":107,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T00:00:00Z","timestamp":1687219200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"BMBF","doi-asserted-by":"publisher","award":["01DN20001"],"award-info":[{"award-number":["01DN20001"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"BMBF","doi-asserted-by":"publisher","award":["16GW0182"],"award-info":[{"award-number":["16GW0182"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"BMBF","doi-asserted-by":"publisher","award":["H2020 MSCA-ITN"],"award-info":[{"award-number":["H2020 MSCA-ITN"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"name":"EU","award":["01DN20001"],"award-info":[{"award-number":["01DN20001"]}]},{"name":"EU","award":["16GW0182"],"award-info":[{"award-number":["16GW0182"]}]},{"name":"EU","award":["H2020 MSCA-ITN"],"award-info":[{"award-number":["H2020 MSCA-ITN"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The gap-junction-coupled astroglial network plays a central role in the regulation of neuronal activity and synchronisation, but its involvement in the pathogenesis of neuronal diseases is not yet understood. Here, we present the current state of knowledge about the impact of impaired glial coupling in the development and progression of epilepsy and discuss whether astrocytes represent alternative therapeutic targets. We focus mainly on temporal lobe epilepsy (TLE), which is the most common form of epilepsy in adults and is characterised by high therapy resistance. Functional data from TLE patients and corresponding experimental models point to a complete loss of astrocytic coupling, but preservation of the gap junction forming proteins connexin43 and connexin30 in hippocampal sclerosis. Several studies further indicate that astrocyte uncoupling is a causal event in the initiation of TLE, as it occurs very early in epileptogenesis, clearly preceding dysfunctional changes in neurons. However, more research is needed to fully understand the role of gap junction channels in epilepsy and to develop safe and effective therapeutic strategies targeting astrocytes.<\/jats:p>","DOI":"10.3390\/cells12121669","type":"journal-article","created":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T01:35:11Z","timestamp":1687311311000},"page":"1669","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Role of Impaired Astrocyte Gap Junction Coupling in Epileptogenesis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0090-7553","authenticated-orcid":false,"given":"Peter","family":"Bedner","sequence":"first","affiliation":[{"name":"Institute of Cellular Neurosciences, Medical Faculty, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2579-8357","authenticated-orcid":false,"given":"Christian","family":"Steinh\u00e4user","sequence":"additional","affiliation":[{"name":"Institute of Cellular Neurosciences, Medical Faculty, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1111\/epi.12550","article-title":"ILAE Official Report: A Practical Clinical Definition of Epilepsy","volume":"55","author":"Fisher","year":"2014","journal-title":"Epilepsia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1212\/WNL.0000000000003509","article-title":"Prevalence and Incidence of Epilepsy: A Systematic Review and Meta-Analysis of International Studies","volume":"88","author":"Fiest","year":"2017","journal-title":"Neurology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1124\/pr.120.019539","article-title":"Drug Resistance in Epilepsy: Clinical Impact, Potential Mechanisms, and New Innovative Treatment Options","volume":"72","author":"Potschka","year":"2020","journal-title":"Pharmacol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1097\/WCO.0b013e32833735b5","article-title":"Mechanisms of Action of Antiepileptic Drugs: The Search for Synergy","volume":"23","author":"Stafstrom","year":"2010","journal-title":"Curr. Opin. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1002\/glia.23247","article-title":"Epilepsy and Astrocyte Energy Metabolism","volume":"66","author":"Boison","year":"2018","journal-title":"Glia"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2687","DOI":"10.1007\/s11064-021-03236-x","article-title":"Astrocytes and Epilepsy","volume":"46","author":"Binder","year":"2021","journal-title":"Neurochem. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1152\/physrev.00042.2016","article-title":"Physiology of Astroglia","volume":"98","author":"Verkhratsky","year":"2018","journal-title":"Physiol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1152\/physrev.00043.2018","article-title":"Glial Connexins and Pannexins in the Healthy and Diseased Brain","volume":"101","author":"Giaume","year":"2020","journal-title":"Physiol. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/nrn2757","article-title":"Astroglial Networks: A Step Further in Neuroglial and Gliovascular Interactions","volume":"11","author":"Giaume","year":"2010","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1002\/glia.21120","article-title":"Role of Astroglial Connexin30 in Hippocampal Gap Junction Coupling","volume":"59","author":"Gosejacob","year":"2011","journal-title":"Glia"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3420","DOI":"10.1093\/cercor\/bhu157","article-title":"Characterization of Panglial Gap Junction Networks in the Thalamus, Neocortex, and Hippocampus Reveals a Unique Population of Glial Cells","volume":"25","author":"Griemsmann","year":"2015","journal-title":"Cereb. Cortex"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1002\/glia.23196","article-title":"Subcellular Reorganization and Altered Phosphorylation of the Astrocytic Gap Junction Protein Connexin43 in Human and Experimental Temporal Lobe Epilepsy","volume":"65","author":"Deshpande","year":"2017","journal-title":"Glia"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1002\/glia.23725","article-title":"Properties of Human Astrocytes and NG2 Glia","volume":"68","author":"Bedner","year":"2020","journal-title":"Glia"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1111\/j.1469-7793.1999.0631n.x","article-title":"Biophysical Properties of Mouse Connexin30 Gap Junction Channels Studied in Transfected Human HeLa Cells","volume":"519","author":"Valiunas","year":"1999","journal-title":"J. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"E42","DOI":"10.1161\/01.RES.86.2.e42","article-title":"Formation of Heterotypic Gap Junction Channels by Connexins 40 and 43","volume":"86","author":"Valiunas","year":"2000","journal-title":"Circ. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1042\/BJ20082319","article-title":"Connexin43 Phosphorylation: Structural Changes and Biological Effects","volume":"419","author":"Solan","year":"2009","journal-title":"Biochem. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s00232-001-0017-1","article-title":"Intracellular Domains of Mouse Connexin26 and -30 Affect Diffusional and Electrical Properties of Gap Junction Channels","volume":"181","author":"Manthey","year":"2001","journal-title":"J. Membr. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1002\/glia.21073","article-title":"Functional Heterotypic Interactions between Astrocyte and Oligodendrocyte Connexins","volume":"59","author":"Magnotti","year":"2011","journal-title":"Glia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"88","DOI":"10.3389\/fphar.2013.00088","article-title":"Connexin and Pannexin Hemichannels in Brain Glial Cells: Properties, Pharmacology, and Roles","volume":"4","author":"Giaume","year":"2013","journal-title":"Front. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.1016\/j.bbamem.2011.06.011","article-title":"Non-Channel Functions of Connexins in Cell Growth and Cell Death","volume":"1818","author":"Vinken","year":"2012","journal-title":"Biochim. Biophys. Acta BBA-Biomembr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"11336","DOI":"10.1073\/pnas.0813160106","article-title":"Connexin Expression by Radial Glia-like Cells Is Required for Neurogenesis in the Adult Dentate Gyrus","volume":"106","author":"Kunze","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1002\/glia.22313","article-title":"Astrocyte Dysfunction in Temporal Lobe Epilepsy: K+ Channels and Gap Junction Coupling","volume":"60","author":"Seifert","year":"2012","journal-title":"Glia"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.neuint.2013.01.011","article-title":"Altered Kir and Gap Junction Channels in Temporal Lobe Epilepsy","volume":"63","author":"Bedner","year":"2013","journal-title":"Neurochem. Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1093\/brain\/awv067","article-title":"Astrocyte Uncoupling as a Cause of Human Temporal Lobe Epilepsy","volume":"138","author":"Bedner","year":"2015","journal-title":"Brain"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1007\/s11064-022-03773-z","article-title":"Overview Article Astrocytes as Initiators of Epilepsy","volume":"48","author":"Henning","year":"2022","journal-title":"Neurochem. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1111\/j.1749-6632.1986.tb27157.x","article-title":"Introductory Remarks: Glial-Interstitial Fluid Exchange","volume":"481","author":"Orkand","year":"1986","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/S0197-0186(99)00137-0","article-title":"Role of Astrocytes in the Clearance of Excess Extracellular Potassium","volume":"36","author":"Walz","year":"2000","journal-title":"Neurochem. Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1016\/j.neuroscience.2004.06.008","article-title":"Potassium Buffering in the Central Nervous System","volume":"129","author":"Kofuji","year":"2004","journal-title":"Neuroscience"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1002\/glia.23751","article-title":"Limited Contribution of Astroglial Gap Junction Coupling to Buffering of Extracellular K+ in CA1 Stratum Radiatum","volume":"68","author":"Breithausen","year":"2020","journal-title":"Glia"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5438","DOI":"10.1523\/JNEUROSCI.0037-06.2006","article-title":"The Impact of Astrocytic Gap Junctional Coupling on Potassium Buffering in the Hippocampus","volume":"26","author":"Wallraff","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1113\/JP271958","article-title":"Does Rapid and Physiological Astrocyte\u2013Neuron Signalling Amplify Epileptic Activity?","volume":"595","author":"Henneberger","year":"2017","journal-title":"J. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1002\/glia.21259","article-title":"Gap Junctions Mediate Intercellular Spread of Sodium between Hippocampal Astrocytes in Situ","volume":"60","author":"Langer","year":"2012","journal-title":"Glia"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.tins.2012.04.003","article-title":"Sodium Dynamics: Another Key to Astroglial Excitability?","volume":"35","author":"Kirischuk","year":"2012","journal-title":"Trends Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"451","DOI":"10.3389\/fnmol.2017.00451","article-title":"Astroglial Glutamate Signaling and Uptake in the Hippocampus","volume":"10","author":"Rose","year":"2017","journal-title":"Front. Mol. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1177\/1073858420901474","article-title":"Gliotransmission: A Novel Target for the Development of Antiseizure Drugs","volume":"26","author":"Riquelme","year":"2020","journal-title":"Neuroscientist"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"614923","DOI":"10.3389\/fneur.2020.614923","article-title":"Astrocytic GABA Accumulation in Experimental Temporal Lobe Epilepsy","volume":"11","author":"Timmermann","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"8467","DOI":"10.1073\/pnas.1016650108","article-title":"Astroglial Networks Scale Synaptic Activity and Plasticity","volume":"108","author":"Pannasch","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nbd.2016.12.017","article-title":"Astrocytic Gap Junction Blockade Markedly Increases Extracellular Potassium without Causing Seizures in the Mouse Neocortex","volume":"101","author":"Bazzigaluppi","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"105160","DOI":"10.1016\/j.nbd.2020.105160","article-title":"Neocortical in Vivo Focal and Spreading Potassium Responses and the Influence of Astrocytic Gap Junctional Coupling","volume":"147","author":"EbrahimAmini","year":"2021","journal-title":"Neurobiol. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"110484","DOI":"10.1016\/j.celrep.2022.110484","article-title":"Decoupling Astrocytes in Adult Mice Impairs Synaptic Plasticity and Spatial Learning","volume":"38","author":"Binini","year":"2022","journal-title":"Cell Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1126\/science.1164022","article-title":"Astroglial Metabolic Networks Sustain Hippocampal Synaptic Transmission","volume":"322","author":"Rouach","year":"2008","journal-title":"Science"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"108642","DOI":"10.1016\/j.celrep.2020.108642","article-title":"Astrocytes and Oligodendrocytes in the Thalamus Jointly Maintain Synaptic Activity by Supplying Metabolites","volume":"34","author":"Philippot","year":"2021","journal-title":"Cell Rep."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"G\u00f3mez-Gonzalo, M., Losi, G., Chiavegato, A., Zonta, M., Cammarota, M., Brondi, M., Vetri, F., Uva, L., Pozzan, T., and de Curtis, M. (2010). An Excitatory Loop with Astrocytes Contributes to Drive Neurons to Seizure Threshold. PLoS Biol., 8.","DOI":"10.1371\/journal.pbio.1000352"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1007\/s11064-017-2243-7","article-title":"Connexin Hemichannels in Astrocytes: An Assessment of Controversies Regarding Their Functional Characteristics","volume":"42","author":"Nielsen","year":"2017","journal-title":"Neurochem. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1002\/glia.23341","article-title":"Inhibition of Astroglial Connexin43 Hemichannels with TAT-Gap19 Exerts Anticonvulsant Effects in Rodents","volume":"66","author":"Walrave","year":"2018","journal-title":"Glia"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Walrave, L., Vinken, M., Leybaert, L., and Smolders, I. (2020). Astrocytic Connexin43 Channels as Candidate Targets in Epilepsy Treatment. Biomolecules, 10.","DOI":"10.3390\/biom10111578"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e2213162119","DOI":"10.1073\/pnas.2213162119","article-title":"Inhibition of Connexin Hemichannels Alleviates Neuroinflammation and Hyperexcitability in Temporal Lobe Epilepsy","volume":"119","author":"Guo","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1002\/glia.20598","article-title":"Modulation of Astrocyte P2Y1 Receptors by the Carboxyl Terminal Domain of the Gap Junction Protein Cx43","volume":"56","author":"Scemes","year":"2008","journal-title":"Glia"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1002\/glia.23747","article-title":"Role of Astrocyte Purinergic Signaling in Epilepsy","volume":"68","author":"Nikolic","year":"2020","journal-title":"Glia"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1038\/s41582-022-00727-5","article-title":"Astrocytes in the Initiation and Progression of Epilepsy","volume":"18","author":"Vezzani","year":"2022","journal-title":"Nat. Rev. Neurol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1038\/nn.3662","article-title":"Connexin 30 Sets Synaptic Strength by Controlling Astroglial Synapse Invasion","volume":"17","author":"Pannasch","year":"2014","journal-title":"Nat. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1007\/s004010000305","article-title":"Expression of Connexin 43 and Connexin 32 Gap-Junction Proteins in Epilepsy-Associated Brain Tumors and in the Perilesional Epileptic Cortex","volume":"101","author":"Aronica","year":"2001","journal-title":"Acta Neuropathol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3171\/jns.2006.105.1.77","article-title":"Altered Expression of Connexin Subtypes in Mesial Temporal Lobe Epilepsy in Humans","volume":"105","author":"Collignon","year":"2006","journal-title":"J. Neurosurg."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/0014-4886(91)90007-Y","article-title":"Gap Junction Gene Expression in Human Seizure Disorder","volume":"111","author":"Naus","year":"1991","journal-title":"Exp. Neurol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.neuroscience.2012.06.002","article-title":"Hippocampal Tissue of Patients with Refractory Temporal Lobe Epilepsy Is Associated with Astrocyte Activation, Inflammation, and Altered Expression of Channels and Receptors","volume":"220","author":"Das","year":"2012","journal-title":"Neuroscience"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1006\/exnr.1997.6467","article-title":"Hippocampal Connexin 43 Expression in Human Complex Partial Seizure Disorder","volume":"145","author":"Elisevich","year":"1997","journal-title":"Exp. Neurol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0006-8993(01)03289-9","article-title":"Upregulation in Astrocytic Connexin 43 Gap Junction Levels May Exacerbate Generalized Seizures in Mesial Temporal Lobe Epilepsy","volume":"929","author":"Fonseca","year":"2002","journal-title":"Brain Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1212\/WNL.0b013e31820f2da6","article-title":"Expression of Connexin 43 in the Human Epileptic and Drug-Resistant Cerebral Cortex","volume":"76","author":"Garbelli","year":"2011","journal-title":"Neurology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"S185","DOI":"10.1111\/j.1528-1157.2000.tb01579.x","article-title":"Alterations of Glial Cell Function in Temporal Lobe Epilepsy","volume":"41","author":"Heinemann","year":"2000","journal-title":"Epilepsia"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/S0006-8993(01)03254-1","article-title":"Effects of Barium, Furosemide, Ouabaine and 4,4\u2032-Diisothiocyanatostilbene-2,2\u2032-Disulfonic Acid (DIDS) on Ionophoretically-Induced Changes in Extracellular Potassium Concentration in Hippocampal Slices from Rats and from Patients with Epilepsy","volume":"925","author":"Jauch","year":"2002","journal-title":"Brain Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1046\/j.1460-9568.2000.00103.x","article-title":"Effects of Barium on Stimulus-Induced Rises of [K+]o in Human Epileptic Non-Sclerotic and Sclerotic Hippocampal Area CA1","volume":"12","author":"Kivi","year":"2000","journal-title":"Eur. J. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1046\/j.1460-9568.2000.00104.x","article-title":"Astrocytes in the Hippocampus of Patients with Temporal Lobe Epilepsy Display Changes in Potassium Conductances","volume":"12","author":"Hinterkeuser","year":"2000","journal-title":"Eur. J. Neurosci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S0920-1211(99)00052-2","article-title":"Molecular Neuropathology of Human Mesial Temporal Lobe Epilepsy","volume":"36","author":"Beck","year":"1999","journal-title":"Epilepsy Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1111\/j.1528-1167.2011.03024.x","article-title":"Modern Antiepileptic Drug Development Has Failed to Deliver: Ways out of the Current Dilemma","volume":"52","author":"Schmidt","year":"2011","journal-title":"Epilepsia"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.jneumeth.2015.04.011","article-title":"Chemically-Induced TLE Models: Topical Application","volume":"260","author":"Jefferys","year":"2016","journal-title":"J. Neurosci. Methods"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1523\/ENEURO.0337-20.2021","article-title":"The Kainic Acid Models of Temporal Lobe Epilepsy","volume":"8","author":"Rusina","year":"2021","journal-title":"eNeuro"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1006\/mcne.2002.1155","article-title":"Connexin-30 MRNA Is Up-Regulated in Astrocytes and Expressed in Apoptotic Neuronal Cells of Rat Brain Following Kainate-Induced Seizures","volume":"21","author":"Condorelli","year":"2002","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1046\/j.1460-9568.2003.02910.x","article-title":"Cellular Expression of Connexins in the Rat Brain: Neuronal Localization, Effects of Kainate-Induced Seizures and Expression in Apoptotic Neuronal Cells","volume":"18","author":"Condorelli","year":"2003","journal-title":"Eur. J. Neurosci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1139\/cjpp-2016-0219","article-title":"Effects of Ferulic Acid on Oxidative Stress, Heat Shock Protein 70, Connexin 43, and Monoamines in the Hippocampus of Pentylenetetrazole-Kindled Rats","volume":"95","author":"Hussein","year":"2017","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Kinjo, E.R., Higa, G.S.V., Morya, E., Valle, A.C., Kihara, A.H., and Britto, L.R.G. (2014). Reciprocal Regulation of Epileptiform Neuronal Oscillations and Electrical Synapses in the Rat Hippocampus. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0109149"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.neulet.2006.06.025","article-title":"A Single Evoked Afterdischarge Produces Rapid Time-Dependent Changes in Connexin36 Protein Expression in Adult Rat Dorsal Hippocampus","volume":"405","author":"McCracken","year":"2006","journal-title":"Neurosci. Lett."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1002\/glia.23591","article-title":"Astroglial Cx30 Sustains Neuronal Population Bursts Independently of Gap-Junction Mediated Biochemical Coupling","volume":"67","author":"Pannasch","year":"2019","journal-title":"Glia"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/S0169-328X(00)00195-9","article-title":"Expression of Connexin Genes in Hippocampus of Kainate-Treated and Kindled Rats under Conditions of Experimental Epilepsy","volume":"83","author":"Beck","year":"2000","journal-title":"Mol. Brain Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.nbd.2010.07.018","article-title":"Increased Coupling and Altered Glutamate Transport Currents in Astrocytes Following Kainic-Acid-Induced Status Epilepticus","volume":"40","author":"Takahashi","year":"2010","journal-title":"Neurobiol. Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1007\/s00221-015-4226-8","article-title":"Astrocytic Cx 43 and Cx 40 in the Mouse Hippocampus during and after Pilocarpine-Induced Status Epilepticus","volume":"233","author":"Wu","year":"2015","journal-title":"Exp. Brain Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1002\/jnr.23726","article-title":"Experimental Febrile Seizures Impair Interastrocytic Gap Junction Coupling in Juvenile Mice","volume":"94","author":"Khan","year":"2016","journal-title":"J. Neurosci. Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"15","DOI":"10.5698\/1535-7511-14.s2.15","article-title":"Inflammatory Processes, Febrile Seizures, and Subsequent Epileptogenesis","volume":"14","author":"Choy","year":"2014","journal-title":"Epilepsy Curr."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1038\/s41582-019-0217-x","article-title":"Neuroinflammatory Pathways as Treatment Targets and Biomarkers in Epilepsy","volume":"15","author":"Vezzani","year":"2019","journal-title":"Nat. Rev. Neurol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1096\/fj.05-4297fje","article-title":"Proinflammatory Cytokines Released from Microglia Inhibit Gap Junctions in Astrocytes: Potentiation by \u03b2-Amyloid","volume":"20","author":"Calvo","year":"2006","journal-title":"FASEB J."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"13781","DOI":"10.1523\/JNEUROSCI.2042-07.2007","article-title":"Cx43 Hemichannels and Gap Junction Channels in Astrocytes Are Regulated Oppositely by Proinflammatory Cytokines Released from Activated Microglia","volume":"27","author":"Retamal","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1002\/jnr.21639","article-title":"Implications of Antiinflammatory Properties of the Anticonvulsant Drug Levetiracetam in Astrocytes","volume":"86","author":"Haghikia","year":"2008","journal-title":"J. Neurosci. Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1002\/glia.24265","article-title":"Reactive Microglia Are the Major Source of Tumor Necrosis Factor Alpha and Contribute to Astrocyte Dysfunction and Acute Seizures in Experimental Temporal Lobe Epilepsy","volume":"71","author":"Henning","year":"2023","journal-title":"Glia"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1111\/epi.16910","article-title":"Cell Death of Hippocampal CA1 Astrocytes during Early Epileptogenesis","volume":"62","author":"Wu","year":"2021","journal-title":"Epilepsia"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"L\u00f6scher, W., and Friedman, A. (2020). Structural, Molecular, and Functional Alterations of the Blood-Brain Barrier during Epileptogenesis and Epilepsy: A Cause, Consequence, or Both?. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21020591"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"10588","DOI":"10.1523\/JNEUROSCI.2323-09.2009","article-title":"Astrocytic Dysfunction in Epileptogenesis: Consequence of Altered Potassium and Glutamate Homeostasis?","volume":"29","author":"David","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"8927","DOI":"10.1523\/JNEUROSCI.0430-09.2009","article-title":"Transcriptome Profiling Reveals TGF-\u03b2 Signaling Involvement in Epileptogenesis","volume":"29","author":"Cacheaux","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1111\/j.1528-1167.2012.03665.x","article-title":"Albumin Is Taken up by Hippocampal NG2 Cells and Astrocytes and Decreases Gap Junction Coupling","volume":"53","author":"Braganza","year":"2012","journal-title":"Epilepsia"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"660591","DOI":"10.3389\/fneur.2021.660591","article-title":"Initiation of Experimental Temporal Lobe Epilepsy by Early Astrocyte Uncoupling Is Independent of TGF\u03b2R1\/ALK5 Signaling","volume":"12","author":"Henning","year":"2021","journal-title":"Front. Neurol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1523\/JNEUROSCI.23-03-00766.2003","article-title":"Accelerated Hippocampal Spreading Depression and Enhanced Locomotory Activity in Mice with Astrocyte-Directed Inactivation of Connexin43","volume":"23","author":"Theis","year":"2003","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1093\/hmg\/ddg001","article-title":"Connexin30 (Gjb6)-Deficiency Causes Severe Hearing Impairment and Lack of Endocochlear Potential","volume":"12","author":"Teubner","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"ra6","DOI":"10.1126\/scisignal.aad3066","article-title":"Astroglial Networks Promote Neuronal Coordination","volume":"9","author":"Chever","year":"2016","journal-title":"Sci. Signal."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.1002\/glia.23832","article-title":"Constitutive Deletion of Astrocytic Connexins Aggravates Kainate-Induced Epilepsy","volume":"68","author":"Deshpande","year":"2020","journal-title":"Glia"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1016\/j.bbamem.2011.10.016","article-title":"Functional Redundancy and Compensation among Members of Gap Junction Protein Families?","volume":"1818","author":"Bedner","year":"2012","journal-title":"Biochim. Biophys. Acta BBA-Biomembr."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1152\/jn.00148.2004","article-title":"Carbenoxolone Inhibition of Voltage-Gated Ca Channels and Synaptic Transmission in the Retina","volume":"92","author":"Vessey","year":"2004","journal-title":"J. Neurophysiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1002\/glia.10197","article-title":"Acute Downregulation of Cx43 Alters P2Y Receptor Expression Levels in Mouse Spinal Cord Astrocytes","volume":"42","author":"Suadicani","year":"2003","journal-title":"Glia"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2551","DOI":"10.1007\/s11064-017-2246-4","article-title":"Modulation of Tonic GABA Currents by Anion Channel and Connexin Hemichannel Antagonists","volume":"42","author":"Ransom","year":"2017","journal-title":"Neurochem. Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"RC113","DOI":"10.1523\/JNEUROSCI.20-23-j0003.2000","article-title":"Electrical Coupling and Excitatory Synaptic Transmission between Rhythmogenic Respiratory Neurons in the PreB\u00f6tzinger Complex","volume":"20","author":"Rekling","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1113\/jphysiol.2003.053439","article-title":"Carbenoxolone Blockade of Neuronal Network Activity in Culture Is Not Mediated by an Action on Gap Junctions","volume":"553","author":"Rouach","year":"2003","journal-title":"J. Physiol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.neuropharm.2008.05.001","article-title":"Carbenoxolone Impairs LTP and Blocks NMDA Receptors in Murine Hippocampus","volume":"55","author":"Chepkova","year":"2008","journal-title":"Neuropharmacology"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1152\/jn.00060.2009","article-title":"Direct Actions of Carbenoxolone on Synaptic Transmission and Neuronal Membrane Properties","volume":"102","author":"Tovar","year":"2009","journal-title":"J. Neurophysiol."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Volnova, A., Tsytsarev, V., Ganina, O., V\u00e9lez-Crespo, G.E., Alves, J.M., Ignashchenkova, A., and Inyushin, M. (2022). The Anti-Epileptic Effects of Carbenoxolone In Vitro and In Vivo. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23020663"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1523\/JNEUROSCI.2365-20.2020","article-title":"Exacerbation of Epilepsy by Astrocyte Alkalization and Gap Junction Uncoupling","volume":"41","author":"Onodera","year":"2021","journal-title":"J. Neurosci."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1097\/WNR.0000000000000385","article-title":"Intracellular Spermine Prevents Acid-Induced Uncoupling of Cx43 Gap Junction Channels","volume":"26","author":"Skatchkov","year":"2015","journal-title":"Neuroreport"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1097\/WNR.0000000000000746","article-title":"Polyamines Preserve Connexin43-Mediated Gap Junctional Communication during Intracellular Hypercalcemia and Acidosis","volume":"28","author":"Kucheryavykh","year":"2017","journal-title":"Neuroreport"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1136\/heartjnl-2017-312774","article-title":"Danegaptide for Primary Percutaneous Coronary Intervention in Acute Myocardial Infarction Patients: A Phase 2 Randomised Clinical Trial","volume":"104","author":"Helqvist","year":"2018","journal-title":"Heart"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s00210-009-0473-1","article-title":"Improving Cardiac Gap Junction Communication as a New Antiarrhythmic Mechanism: The Action of Antiarrhythmic Peptides","volume":"381","author":"Dhein","year":"2010","journal-title":"Naunyn. Schmiedebergs Arch. Pharmacol."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Freitas-Andrade, M., Bechberger, J., Wang, J., Yeung, K.K.C., Whitehead, S.N., Shultz Hansen, R., and Naus, C.C. (2020). Danegaptide Enhances Astrocyte Gap Junctional Coupling and Reduces Ischemic Reperfusion Brain Injury in Mice. 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