N,N-dimethyltryptamine mitigates experimental stroke by stabilizing the blood-brain barrier and reducing neuroinflammation.

Summary

DMT significantly reduces infarct volume and mitigates poststroke effects by stabilizing the blood-brain barrier and reducing neuroinflammation. It achieves this through mechanisms such as reducing cerebral edema, attenuating astrocyte dysfunction, and shifting serum protein composition to an anti-inflammatory state. Additionally, DMT suppresses proinflammatory cytokines and chemokines while reducing microglial activation. These findings suggest that DMT could enhance existing stroke therapies.

Study at a glance

Abstract

N,N-dimethyltryptamine (DMT) is a psychoactive molecule present in the human brain. DMT is under clinical evaluation as a neuroprotective agent in poststroke recovery. Yet, its mechanism of action remains poorly understood. In a rat transient middle cerebral artery occlusion stroke model, we previously showed that DMT reduces infarct volume. Here, we demonstrate that this effect is accompanied by reduction of cerebral edema, attenuated astrocyte dysfunction, and a shift in serum protein composition toward an anti-inflammatory, neuroprotective state. DMT restored tight junction integrity and blood-brain barrier (BBB) function in vitro and in vivo. DMT suppressed the release of proinflammatory cytokines and chemokines in brain endothelial cells and peripheral immune cells and reduced microglial activation via the sigma-1 receptor. Our findings prove that DMT mitigates a poststroke effect by stabilizing the BBB and reducing neuroinflammation. Such interactions of DMT with the vascular and immune systems can be leveraged to complement current, insufficient, stroke therapy.