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In this study, we explored whether astrocytic Cx43 forms hemichannels (HCs) that contribute to seizure progression in temporal lobe epilepsy (TLE) in mice. We focused on how these HCs influence the permeability of the blood\u2010brain barrier (BBB), a crucial factor in the pathophysiology of epilepsy. Immunofluorescence staining and western blot analysis were employed to assess Cx43 expression in kainic acid\u2010induced TLE mice, while BBB permeability was evaluated in TLE mice and those treated with TAT\u2010Gap19 (an astrocytic Cx43 HC inhibitor) using Evans Blue permeation, serum S100\u03b2 protein quantification, ZO\u20101 expression, and albumin extravasation into brain parenchyma via western blotting. Furthermore, seizure burden was monitored continuously using telemetric electroencephalography (EEG) and video monitoring in epileptic and TAT\u2010Gap19\u2010treated mice. Results demonstrated a significant increase in Cx43 content in hippocampal tissue in the TLE group, with a pronounced expression around blood vessels. TAT\u2010GAP19 treatment alleviated EEG seizures and BBB permeability in TLE mice. These findings suggest that astrocytic Cx43 HCs in the hippocampus play a crucial role in epileptogenesis and seizure progression by regulating BBB permeability. Targeting Cx43\u2010formed HCs distributed around the neurovascular unit may offer a novel therapeutic approach for epilepsy.<\/jats:p>","DOI":"10.1002\/pdi3.2500","type":"journal-article","created":{"date-parts":[[2024,8,2]],"date-time":"2024-08-02T09:27:10Z","timestamp":1722590830000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Astrocytic connexin 43\u2010hemichannels aggravate seizures by modulating blood\u2010brain barrier permeability in temporal lobe epilepsy mice"],"prefix":"10.1002","volume":"2","author":[{"given":"Honghong","family":"Song","sequence":"first","affiliation":[{"name":"Department of Neurology Children\u2019s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders Ministry of Education Key Laboratory of Child Development and Disorders Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders  Chongqing 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