A single intraperitoneal dose of DMT (1 mg/kg) followed by a 24-hour infusion (2 mg/kg/h) reduced ischemic brain lesion volume and improved functional recovery in male Wistar rats after 60 minutes of transient middle cerebral artery occlusion. The neuroprotective effect was blocked by a Sigma-1 receptor antagonist, indicating a Sigma-1 receptor-dependent mechanism. DMT treatment lowered expression of the pro-apoptotic protein APAF1, increased brain-derived neurotrophic factor (BDNF), and shifted the inflammatory cytokine profile toward an anti-inflammatory state (decreased TNF-α, IL-1β, IL-6; increased IL-10). The findings suggest DMT protects against ischemic injury through combined anti-apoptotic, pro-neurotrophic, and anti-inflammatory actions.
In a rat stroke model, DMT reduces brain damage by decreasing swelling, restoring the blood-brain barrier, and shifting the body toward an anti-inflammatory state. DMT also suppresses inflammatory signals from brain and immune cells via the sigma-1 receptor. These effects suggest DMT could complement existing stroke therapies.
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.