Astrocytic Igfbp2 Promotes Spontaneous Seizures in a Mouse Model of Mesial Temporal Lobe Epilepsy

Mesial temporal lobe epilepsy (MTLE) is a common, frequently drug-resistant epilepsy characterized by seizures arising from the hippocampus. 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-associated virus (AAV)-mediated labeling with translating ribosomal affinity purification (TRAP) to generate astrocyte-enriched transcriptome profiles from sclerotic hippocampal regions in a mouse model of MTLE. This analysis identified a marked upregulation of insulin-like growth factor-binding 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.