Blocking microglial reactivity via purinergic receptors prevents subacute cognitive deficits after TIA

Llovera, Gemma and Heindl, Steffanie and Varga, Dániel P. and Lénárt, Nikolett and Kallabis, Sebastian and Göb, Vanessa and Stegner, David and Escaig, Raphael and Nicolai, Leo and Franzmeier, Nicolai and Meissner, Felix and Dénes, Ádám and Liesz, Arthur (2026) Blocking microglial reactivity via purinergic receptors prevents subacute cognitive deficits after TIA. EMBO MOLECULAR MEDICINE, 18 (4). pp. 1150-1173. ISSN 1757-4676 (print); 1757-4684 (online)

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Abstract

Our research presents a new animal model of transient ischemic attack (TIA) that mimics brief episodes without cell loss, but results in neuronal and behavioral deficits. We identified excessive microglial reactivity, driven by acute ATP release, as a key factor in post-TIA neurological deficits, which were ameliorated by inhibiting the P2Y12 receptor, a microglia-specific purinergic receptor in the brain parenchyma responsible for activity-dependent microglial cell-cell interactions. This finding suggests that modulation of microglial reactivity offers a promising strategy to prevent cognitive impairment in TIA patients, opening avenues for future research in this underexplored area.

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