Lemborexant Reduces Infarct Volume and Improves Long-Term Functional Recovery in a Murine Model of Ischemic Stroke

Area of Science:

• Neuroscience
• Pharmacology
• Stroke Research

Background:

• Ischemic stroke recovery is variable and often incomplete, with sleep fragmentation negatively impacting outcomes.
• Current sleep aids can disrupt sleep architecture and neuroplasticity, highlighting the need for novel therapeutic approaches.
• Lemborexant, a dual orexin receptor antagonist, promotes sleep by enhancing continuity and suppressing wakefulness.

Purpose of the Study:

• To investigate the effects of lemborexant on sleep disturbances, infarct volume, and functional recovery in a rodent model of ischemic stroke.
• To compare lemborexant's effects with zolpidem, a common sleep-promoting agent, in the context of stroke recovery.

Main Methods:

• Rodent models of ischemic stroke were treated with lemborexant (10 and 30 mg/kg) or zolpidem (30 mg/kg).
• Sleep macrostructure, fragmentation, and EEG spectra were analyzed.
• Infarct volume and functional recovery (limb use) were assessed following drug administration.

Main Results:

• Lemborexant (30 mg/kg) increased NREM sleep percentage and preserved sleep continuity in both healthy and stroke models.
• Zolpidem increased NREM sleep but also exacerbated sleep fragmentation.
• Lemborexant treatment significantly reduced infarct volume and improved impaired limb use in stroke model mice.

Conclusions:

• Lemborexant stabilizes sleep and promotes structural and functional recovery following experimental stroke in rodents.
• These findings support lemborexant's potential as a novel therapeutic intervention for improving post-stroke recovery.
• Targeted sleep modulation with lemborexant may offer a neurorestorative approach in subacute stroke care.