Introduction: N,N-Dimethyltryptamine is a natural hallucinogen, the active ingredient of the brew called ayahuasca consumed by Amazonian tribes for spiritual purposes. While DMT occurs in small quantities in the human body its role is not fully understood. Previous research has demonstrated the in vitro beneficial effects of DMT on cell survival in ischemic environments mediated by the Sigma-1 receptor signalling pathway. Our research group was the first to demonstrate the in vivo neuroprotective effects of DMT using a rat stroke model. Significant reductions in lesion size were observed in DMT-treated animals using MRI, along with significantly improved functional regeneration of affected limbs. The decrease in lesion size observed on T2 sequences may be attributed to reduced peri-infarct edema. The damage of the blood-brain barrier plays a crucial role in the development of edema during ischemia.
Objective: Morphological examination of the effect of DMT treatment on blood-brain barrier integrity following experimental stroke.
Methods: In our rat stroke model 60-minute transient middle cerebral artery occlusion was induced using filament occlusion technique in Wistar rats. Animals were divided into three groups (n=5=5=5). The control group received no treatment. The first treated group received continuous DMT (2mg/kg/hr) for 24 hours. The other treated group received simultaneous treatment with a Sigma-1 receptor antagonist (2mg/kg/hr) for 24 hours alongside DMT. The drugs were administered using intraperitoneal osmotic pumps implanted in the abdomen at the onset of reperfusion. After this period the animals were sacrificed, brain sections were prepared for immunohistological analysis and aquaporin-4 and claudin-5 proteins were examined.
Results: In the DMT-treated group significantly reduced aquaporin-4 intensity (p=0.0317) and significantly increased claudin-5 intensity (p=0.0079) were observed compared to the untreated group. The protective effect of DMT on the blood-brain barrier was not evident with simultaneous treatment with the Sigma-1 receptor antagonist.
Discussion: Based on our morphological examination, DMT improved blood-brain barrier integrity following focal cerebral ischemia. The Sigma-1 receptor plays an important role in the effect of DMT on the blood-brain barrier. DMT could be a potential addition to reperfusion in stroke treatment.