László, János Marcell and Vigh, Judit Piroska and Kocsis, Anna and Porkoláb, Gergő and Hoyk, Zsófia and Polgár, Tamás Ferenc and Walter, Fruzsina and Szabó, Attila and Djurovic, Srdjan and Merkely, Béla Péter and Alpár, Alán and Frecska, Ede and Nagy, Zoltán and Deli, Mária Anna and Nardai, Sándor (2025) N , N -dimethyltryptamine mitigates experimental stroke by stabilizing the blood-brain barrier and reducing neuroinflammation. SCIENCE ADVANCES, 11 (33). ISSN 2375-2548
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Abstract
N , N -dimethyltryptamine (DMT) is a psychoactive molecule present in the human brain. DMT is under clinical evaluation as a neuroprotective agent in poststroke recovery. Yet, its mechanism of action remains poorly understood. In a rat transient middle cerebral artery occlusion stroke model, we previously showed that DMT reduces infarct volume. Here, we demonstrate that this effect is accompanied by reduction of cerebral edema, attenuated astrocyte dysfunction, and a shift in serum protein composition toward an anti-inflammatory, neuroprotective state. DMT restored tight junction integrity and blood-brain barrier (BBB) function in vitro and in vivo. DMT suppressed the release of proinflammatory cytokines and chemokines in brain endothelial cells and peripheral immune cells and reduced microglial activation via the sigma-1 receptor. Our findings prove that DMT mitigates a poststroke effect by stabilizing the BBB and reducing neuroinflammation. Such interactions of DMT with the vascular and immune systems can be leveraged to complement current, insufficient, stroke therapy.
| Item Type: | Article |
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| Additional Information: | Funding Agency and Grant Number: National Research, Development and Innovation Office of Hungary [PD137565, K143766] Funding text: The project was funded by the National Research, Development and Innovation Office of Hungary (PD137565 to S.N. and K143766 to M.A.D.) and the Hungaria (PD137565 to S.N. and K143766 to M.A.D.) and the Hungarian An Academy of Sciences (2017-1.2.1-NKP-2017-00002 to A.A. and NAP2022-I-6/2022 to A.A. and M.A.D.). J.P.V., A.E.K., and T.P. were awarded by the New National Excellence Program of the Ministry for Innovation and Technology from the Source of the National Research Development and Innovation Fund (& Uacute;NKP-23-3-SZTE-535; EKOEP-24-2-SZTE-449 and EKOEP-24-4-SZTE-393).This work was supported by the Excellence Program for Higher Education of Hungary (TKP-EGA-25 to A.A.). |
| Subjects: | R Medicine / orvostudomány > RC Internal medicine / belgyógyászat > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry / idegkórtan, neurológia, pszichiátria |
| SWORD Depositor: | MTMT SWORD |
| Depositing User: | MTMT SWORD |
| Date Deposited: | 11 Mar 2026 13:45 |
| Last Modified: | 11 Mar 2026 13:45 |
| URI: | https://real.mtak.hu/id/eprint/235568 |
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