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Its hallmark pathology is hippocampal sclerosis with neuronal loss and reactive astrogliosis. Although astrocytes have emerged as potential targets for antiepileptic therapies, their role in epilepsy development remains poorly defined. Here, we combined adeno\u2010associated virus (AAV)\u2010mediated labeling with translating ribosomal affinity purification (TRAP) to generate astrocyte\u2010enriched transcriptome profiles from sclerotic hippocampal regions in a mouse model of MTLE. This analysis identified a marked upregulation of insulin\u2010like growth factor\u2010binding protein 2 (Igfbp2) in reactive astrocytes. Functional studies revealed that astrocytic Igfbp2 increases the excitability of dentate granule cells and promotes spontaneous recurrent seizures. These findings reveal Igfbp2 as a key astrocytic modulator of hippocampal excitability and identify it as a potential therapeutic target for epilepsy.<\/jats:p>","DOI":"10.1002\/glia.70099","type":"journal-article","created":{"date-parts":[[2025,11,15]],"date-time":"2025-11-15T08:19:22Z","timestamp":1763194762000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Astrocytic Igfbp2 Promotes Spontaneous Seizures in a Mouse Model of Mesial Temporal Lobe Epilepsy"],"prefix":"10.1002","volume":"74","author":[{"given":"Shinichi","family":"Kinoshita","sequence":"first","affiliation":[{"name":"Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences The University of Tokyo  Bunkyo\u2010ku Tokyo 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