Introduction: Ischemic stroke presents a significant burden of mortality and long-term disability globally, highlighting the pressing need for advancements in stroke care and therapeutic interventions. Despite notable progress in acute stroke management, effective neuroprotective strategies remain elusive, underscoring the urgency to address the devastating consequences of ischemic stroke. Dimethyltryptamine (DMT) emerges as a potential neuroprotectant, offering promise in mitigating neuronal damage induced by ischemic insults. Understanding the intricate mechanisms underlying DMT’s neuroprotective effects, particularly in the context of ischemic stroke, holds immense potential for improving stroke care and patient outcomes. In this study, we aim to investigate the role of Sigma-1 receptors in mediating DMT’s neuroprotective actions using a middle cerebral artery occlusion (MCAO) model in C57BL/6 and Sigma-1 receptor knockout mice. By elucidating the interplay between DMT, Sigma-1 receptors, and ischemic stroke pathology, we aspire to contribute to the development of innovative therapeutic strategies that address the unmet needs in stroke management and drive advancements in neuroprotective interventions.

Materials and methods: We employed a total of 16 groups in this study, with 8 groups subjected to a 24hour survival period post middle cerebral artery occlusion (MCAO) induction and another 8 groups undergoing a 30-day survival period. Each group consisted of 5-9 C57BL/6 wild-type or Sigma-1 receptor knockout mice. Following survival, functional and behavioral tests were conducted to assess neurological deficits and depressive symptoms post-stroke, including the staircase test and the forced swimming test. Additionally, histological analysis, protein analysis, and RNA analysis were performed on brain tissue samples to investigate the molecular mechanisms underlying the neuroprotective effects of DMT and the involvement of Sigma-1 receptors.

Results: Our results will be presented.

Discussion: The results will be discussed to elucidate the neuroprotective role of Sigma-1 receptors in DMT’s mechanism of action, addressing potential therapeutic implications and suggesting future research directions.