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Natural compound reduces stroke damage in lab and animals
A naturally occurring molecule, dimethyltryptamine (DMT), has shown early potential to limit brain injury after ischemic stroke by preserving the blood–brain barrier (BBB) and suppressing neuroinflammation. Researchers at the HUN-REN Biological Research Centre (BRC) Institute of Biophysics and the Semmelweis University Heart and Vascular Centre report these findings in a study published in Science Advances. The team combined cellular models and rodent stroke experiments to test how DMT affects vascular and immune responses in the injured brain.
Study overview and key findings
The investigators observed a meaningful reduction in infarct volume (the area of dead tissue caused by stroke) and decreased edema formation in a rat model treated with DMT. In parallel in vitro experiments using brain endothelial cells and astroglial cultures showed that DMT helped restore tight junction architecture and barrier function after injury-like insults. The study also reports diminished production of inflammatory cytokines in both brain endothelial cells and peripheral immune cells, together with reduced activation of microglia — the brain’s resident immune cells.
Co-authors of the study from the Biological Barriers Research Group of the Institute of Biophysics, HUN-REN BRC Szeged (from left to right: Anna Kocsis, Zsófia Hoyk, Mária Deli, Fruzsina Walter, Judit Vigh). Credit: Fruzsina Walter
Co-lead author Mária Deli commented on the translational potential: “It is remarkable how naturally occurring compounds can point to new therapeutic strategies for complex disorders such as stroke.” Co-first author Marcell László summarized experimental outcomes, noting that DMT treatment correlated with measurable improvements in vascular integrity and reduced secondary inflammatory damage.
Mechanisms: blood–brain barrier protection and immune modulation
The study proposes dual mechanisms by which DMT may protect the post-stroke brain. First, DMT appears to stabilize the blood–brain barrier — the selective endothelial interface that shields neural tissue from harmful circulating factors. Preservation of BBB structure limits edema and prevents peripheral immune cells and plasma proteins from exacerbating tissue injury.
Second, DMT reduces neuroinflammation. Treated endothelial and immune cell cultures produced lower levels of pro-inflammatory cytokines, and microglial activation was attenuated. The authors identify Sigma-1 receptors as a likely mediator of these effects. Sigma-1 receptors are chaperone-like proteins expressed in neurons and glia that modulate cellular stress responses, calcium signaling, and inflammation. By engaging these receptors, DMT may shift injured brain tissue toward protective signaling pathways that preserve cell viability and barrier function.
Why targeting the blood–brain barrier matters
The blood–brain barrier is a central therapeutic target for acute stroke because its disruption underlies much of the secondary injury that follows ischemia. Current clinical treatments — such as thrombolysis and endovascular thrombectomy — focus on restoring blood flow but do not directly repair the BBB or control delayed neuroinflammation. A compound that both supports barrier integrity and dampens inflammatory cascades could therefore complement reperfusion therapies and improve functional recovery.
Clinical prospects and limitations
DMT is already known as an endogenous trace amine and is present in small amounts in the human brain. Its psychoactive properties have prompted clinical trials in other neurological and psychiatric contexts, and this new preclinical data supports exploration of DMT-based approaches for stroke recovery. The authors and commentators note important caveats: long-term safety, optimal dosing, timing relative to reperfusion therapies, and potential psychoactive side effects must be fully evaluated in controlled clinical trials.
Judit Vigh, co-first author of the study, emphasizes the translational angle: “Therapeutic options for stroke remain limited; combining barrier-protective and anti-inflammatory effects represents a promising, multi-target approach that could be used alongside existing treatments.”
Expert Insight
Dr. Elena Márquez, neurologist and translational researcher (fictional), says: “These results are encouraging because they tackle two of the hardest problems in acute stroke care: limiting BBB breakdown and curbing harmful inflammation. If subsequent trials confirm safety and efficacy, DMT-derived molecules or Sigma-1 receptor modulators could become valuable adjuncts to reperfusion therapy. The key will be defining a therapeutic window and minimizing central nervous system side effects.”
Conclusion
Preclinical results from Hungarian laboratories point to DMT as a potentially valuable modulator of blood–brain barrier integrity and post-stroke neuroinflammation, acting at least in part through Sigma-1 receptors. While promising, these findings remain early-stage: controlled clinical trials and detailed safety assessments are required before DMT or related compounds can be recommended as part of standard stroke care. Continued research into BBB-targeted therapies and immune modulation could expand the toolkit for improving recovery after ischemic brain injury.
Source: scitechdaily
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