ABSTRACT NUMBER: ESOC2026YS125 DIMETHYLTRYPTAMINE INHIBITS SPREADING DEPOLARISATION IN BRAIN SLICES OF SIGMA-1 RECEPTORKNOCKOUT MICE
European Stroke Journal May 1, 2026 Anna Zsigmond, Rita Frank, Botond Eröss et al.
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.