Dexmedetomidine Alleviates Hippocampal Tissue Damage in Rapid Eye Movement Sleep-Deprived Rats by Activating BDNF/TrkB Signaling Pathway.

INTRODUCTION: Sleep deprivation often leads to marked neurobehavioral and cognitive deficits, yet few well-defined interventions exist to address these effects. Dexmedetomidine (DEX), a highly selective α(2)-adrenoceptor agonist, possesses sedative, hypnotic, analgesic, and sympathetic-blocking properties, closely mimic natural sleep state. In this study, we aim to investigate whether DEX protects hippocampal tissue against rapid eye movement sleep deprivation (RSD)-induced injury in rats and to explore the underlying molecular mechanisms. METHODS: In this study, a rapid eye movement sleep deprivation (RSD) rat model was created using a modified multi-platform method. The influence of dexmedetomidine (DEX) on hippocampal tissue morphology, the BDNF/TrkB signaling pathway, and cognitive function was then evaluated. Group comparisons were analyzed using one-way ANOVA followed by appropriate post hoc tests. RESULTS: In comparison with the control group, DEX significantly alleviated the impaired spatial learning and memory as reflected escape latency and increased the time spent in the garget quadrant. ANA-12 reversed these improvements, indicating DEX's cognitive benefits. HE staining showed that DEX protected neurons from RSD-induced injury by preserving structural integrity and TUNEL assay demonstrated reduced neuron apoptosis in the DEX group. Co-treatment with ANA-12 abolished these protective effects, resulting in neuronal damage and apoptosis levels similar to those observed in RSD rats. Moreover, compared with the level of TNA alpha in RSD rats, IL 6, IL 1beta and MDA levels were lower in the hippocampus of DEX group, while SOD activity was enhanced. Western blot analysis revealed that DEX increased hippocampal BDNF (0.586 ± 0.036 vs 0.315 ± 0.034, ~1.86‑fold, P < 0.01), TrkB (0.774 ± 0.039 vs 0.518 ± 0.033, ~1.49‑fold, P < 0.01) and pro-TrkB expression. However, co-administration of ANA‑12 abolished these effects, returning expression levels close to those in the RSD group, implying that DEX's neuroprotection is mediated via the BDNF/TrkB pathway. CONCLUSION: These findings indicate that DEX exerts neuroprotective effects in RSD by activating the BDNF/TrkB pathway, offering valuable evidence for DEX-based therapeutic approaches to sleep deprivation-related brain injury.