Related Experiment Video
Updated: Feb 8, 2026

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
Published on: August 23, 2024
Orexin dual receptor antagonist attenuates neurological deficits possibly via PI3K/Akt/mTOR pathway activation in
Lili Wang1, Xinli Xiong2, Baofeng Wang3
1Department of Neurology, Shanghai Oriental Clinical Medical College, Nanjing Medical University, Shanghai, China; Department of Neurology, Songjiang Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Background:
Post-stroke sleep disorders are frequent complications of ischemic stroke and contribute to poor neurological recovery. Dual orexin receptor antagonists (DORAs) promote sleep via mechanisms distinct from traditional hypnotics. This study investigated whether almorexant attenuates sleep deprivation (SD)-aggravated ischemic injury in rats and explored the its potential association with PI3K/Akt/mTOR signaling pathway.
Methods:
Male Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (MCAO), and were assigned to sham, MCAO, MCAO+SD, MCAO+SD+almorexant, or MCAO+SD+estazolam. Neurological function (Zea-Longa score, open-field test), infarct volume (TTC), histopathology (H&E), neuronal apoptosis (TUNEL), and PI3K/Akt/mTOR expression (Western blot, RT-qPCR) were assessed.
Results:
SD exacerbated neurological deficits after MCAO, as reflected by higher Zea-Longa scores and impaired locomotor activity. Almorexant treatment was associated with improved behavioral performance and reduced histologic injury, neuronal apoptosis in sleep-deprived MCAO rats. At the molecular level, both almorexant and estazolam treatments were associated with upregulated PI3K, Akt, and mTOR expression at both protein and mRNA levels.
Conclusion:
Almorexant was associated with attenuation of SD-exacerbated ischemic brain injury in rats, accompanied by alterations in PI3K/Akt/mTOR signaling, suggesting DORAs may have potential relevance for the management of post-stroke insomnia.
Related Concept Videos
PI3K/mTOR/AKT Signaling Pathway
Insufficient Sleep and Sleep Deprivation
Sleep deprivation is a more severe form of sleep loss...
Drug-Receptor Interaction: Antagonist
Antagonists can be classified as competitive or noncompetitive based on their...
Antiasthma Drugs: Muscarinic Receptor Antagonists
Antimuscarinic agents compete with ACh for the same binding site on the muscarinic receptors. By binding to these receptors, they inhibit the downstream effects of ACh and block the parasympathetic...
Insulin: The Receptor and Signaling Pathways
Adrenergic Antagonists: ɑ and β-Receptor Blockers

