PhD Scientific Days 2026

Poster Session 2.M - Neurosciences

Neuroprotective and Blood–Brain Barrier–Stabilizing Effects of N,N-Dimethyltryptamine under Ischemia–Reperfusion Conditions

Name of the presenter

László, János Marcell

Institute/workplace of the presenter

Semmelweis University, Heart and Vascualr Center

Authors

János Marcell László Dr.¹
1: Semmelweis University, Heart and Vascualr Center

Text of the abstract

Introduction: Ischemic stroke causes complex injury to the neurovascular unit, leading to blood-brain barrier (BBB) breakdown, edema formation, neuroinflammation, and secondary lesion expansion. Because current reperfusion therapies are applicable only to a limited proportion of patients, adjunct neuroprotective strategies remain highly needed. DMT is an endogenous compound that rapidly crosses the BBB and interacts with multiple receptor systems, including the sigma-1 receptor.

Aims: We investigated whether DMT administered at reperfusion exerts neuroprotective effects in ischemia-reperfusion injury, and whether these effects are related to preservation of BBB integrity and improvement of long-term functional recovery. We also aimed to explore sigma-1 receptor-dependent and -independent mechanisms.

Methods: Transient middle cerebral artery occlusion was induced in male Wistar rats for 60 minutes, followed by reperfusion. DMT treatment was started at reperfusion and was maintained for 24 hours; in one group, the sigma-1 receptor antagonist BD1063 was co- administered. Lesion volume was assessed histologically and by MRI. BBB damage, edema, microglial activation, inflammatory and apoptotic markers, serum biomarkers, BDNF levels, and motor recovery were evaluated. In parallel, an in vitro triple co-culture BBB model exposed to oxygen-glucose deprivation/reoxygenation was used to assess barrier integrity, cell viability, permeability, and endothelial inflammatory responses.

Result: DMT significantly reduced infarct size and cerebral edema, improved BBB integrity, and attenuated ischemia-induced barrier dysfunction in vitro. Treatment stabilized claudin-5, reduced AQP4 redistribution, suppressed central and peripheral inflammatory responses, decreased microglial activation, and downregulated apoptosis-related signaling. DMT-treated animals showed improved long-term motor recovery and increased BDNF levels. The findings indicate that the protective effects of DMT are mediated through both sigma-1 receptor- dependent and -independent pathways.

Conclusion: DMT exerts pleiotropic neuroprotective effects after focal cerebral ischemia by preserving BBB structure and function, reducing neuroinflammation and edema, and promoting neuroplasticity. These findings support the potential of DMT as a future adjunct therapy in ischemic stroke.

Funding: No external funding.