Hungarian Centre of Excellence for Molecular Medicine - University of Szeged Cerebral Blood Flow and Metabolism Research Group, Somogyi u. 4, Szeged, 6720, Hungary; Department of Cell Biology and Molecular Medicine, Albert Szent-Györgyi School of Medicine and Faculty of Science and Informatics, University of Szeged, Somogyi u. 4, Szeged, 6720, Hungary.
2 papers in the library · 67 citations · publishing 2021-2026
Dimethyltryptamine (DMT), a natural compound that activates sigma-1 receptors, reduced spreading depolarizations—waves of electrical disruption in the brain that worsen stroke injury—in rats subjected to global forebrain ischemia. DMT also decreased the number of dying cells and supported astrocyte survival. The protective effects were shared by a selective sigma-1 receptor agonist and were blocked by a sigma-1 receptor antagonist, indicating the receptor mediates the protection. DMT remained effective even when serotonin receptors were blocked. These results suggest DMT could be an additional treatment for acute stroke.
In acute ischemic stroke, spreading depolarizations worsen neuronal injury. The sigma-1 receptor agonist dimethyltryptamine (DMT) reduced the cortical area affected by spreading depolarizations in both wild-type and sigma-1 receptor knockout mice (53.3% vs. 65.7% in wild-type, 42.1% vs. 61.0% in knockout). In knockout animals only, DMT also reduced the area under the curve of depolarizations (299.9 vs. 543.3 mV·s) and their propagation velocity (2.6 vs. 3.8 mm/min). NeuN-positive cell numbers tended to increase with DMT. Surprisingly, DMT was more effective in knockout mice, indicating its neuroprotective effects involve aminergic receptors alongside sigma-1 receptor activation, supporting potential adjuvant use in stroke treatment.