Tóth, Réka and Törteli, Anna and Szabó, Melinda and Stelczerné Kovács, Noémi and Horváth, Ildikó and Farkas, Elek Attila and Frank, Rita and Szigeti, Krisztián and Bari, Ferenc and Krizbai, István Adorján and Máthé, Domokos and Menyhárt, Ákos and Farkas, Eszter (2026) Trifluoperazine reduces infarct size, restores neurovascular coupling and improves early outcomes in experimental acute ischemic stroke. JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM. ISSN 0271-678X (In Press)
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Abstract
Cerebral edema and neurovascular dysfunction are reliable predictors of outcome after acute ischemic stroke (AIS), yet effective targeted therapies remain limited. We investigated the therapeutic potential of trifluoperazine (TFP), an FDA-approved antipsychotic and calmodulin inhibitor that modulates astrocytic aquaporin-4 expression. TFP administered after recanalization in a mouse model of AIS reduced infarct volume and improved early neurological recovery. Importantly, TFP restored neurovascular coupling and enhanced cerebral blood flow responses to spreading depolarizations, indicating improved cerebrovascular function. Mechanistic studies in acute brain slice preparations demonstrated that TFP attenuates cytotoxic tissue swelling, suppresses spreading depolarizations, reduces aquaporin-4 expression and preserves neuronal integrity under osmotic stress. These findings suggest that transient modulation of astrocytic cytotoxic edema and vascular reactivity represents a viable strategy to improve early stroke outcomes. Given its established clinical use, TFP emerges as a promising candidate for therapeutic repurposing in AIS.
| Item Type: | Article |
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| Additional Information: | Funding Agency and Grant Number: Albert Szent-Gyrgyi Medical School; szegedi tudomnyegyetem; European Union [739593]; national research, development and innovation office [K146725, FK142218, K135425, STARTING_24 150356, HUN-REN RGH151414, and TKP2021-EGA-09]; magyar tudomnyos akadmia; Jnos Bolyai Research Fellowship [BO/00254/25] Funding text: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The EU's Horizon 2020 research and innovation program grant number 739593; the National Research, Development and Innovation Office of Hungary (grant numbers K146725, FK142218, K135425, STARTING_24 150356, HUN-REN RGH151414, and TKP2021-EGA-09); the Janos Bolyai Research Fellowship (BO/00254/25) and the National Brain Research Program 3.0 of the Hungarian Academy of Sciences; the Research Fund of the Albert Szent-Gyorgyi Medical School, University of Szeged, Hungary; and the University of Szeged Open Access Fund (nr. 8679). |
| Uncontrolled Keywords: | Acute ischemic stroke, aquaporin-4, neurovascular coupling, spreading depolarization, trifluoperazine |
| Subjects: | Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában |
| SWORD Depositor: | MTMT SWORD |
| Depositing User: | MTMT SWORD |
| Date Deposited: | 24 Sep 2026 07:06 |
| Last Modified: | 24 Sep 2026 07:06 |
| URI: | https://real.mtak.hu/id/eprint/247382 |
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