Melatonin Offers Dual-Phase Protection to Brain Vessel Endothelial Cells in Prolonged Cerebral Ischemia-Recanalization Through Ameliorating ER Stress and Resolving Refractory Stress Granule

Lu, Danli; Liu, Yuxin; Huang, Huipeng; Hu, Mengyan; Li, Tiemei; Wang, Shisi; Shen, Shishi; Wu, Ruizhen; Cai, Wei; Lu, Tingting; Lu, Zhengqi

doi:10.1007/s12975-022-01084-7

Cited by 2 publications

(1 citation statement)

References 52 publications

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“…Given that the circadian rhythm is involved in regulating various pathophysiological mechanisms of IS, some components of the circadian system may be therapeutic targets for IS. Studies have confirmed that exogenous melatonin administration attenuated ischemic stroke injury, improved neurological deficits, and protected the integrity of the blood-brain barrier (BBB) [ 70 , 71 ]. REV-ERBα agonists (e.g., SR9009), acting as pharmacological regulators of the circadian rhythm, inhibited neuronal apoptosis during early brain injury after subarachnoid hemorrhage [ 72 ].…”

Section: Ischemic Strokementioning

confidence: 99%

The Role of Circadian Rhythm in Neurological Diseases: A Translational Perspective

2023

Aging dis

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Intrinsic biological clocks drive the circadian rhythm, which coordinates the physiological and pathophysiological processes in the body. Recently, a bidirectional relationship between circadian rhythms and several neurological diseases has been reported. Neurological diseases can lead to the disruption of circadian homeostasis, thereby increasing disease severity. Therefore, optimizing the current treatments through circadian-based approaches, including adjusted dosing, changing lifestyle, and targeted interventions, offer a promising opportunity for better clinical outcomes and precision medicine. In this review, we provide detailed implications of the circadian rhythm in neurological diseases through bench-to-bedside approaches. Furthermore, based on the unsatisfactory clinical outcomes, we critically discuss the potential of circadian-based interventions, which may encourage more studies in this discipline, with the hope of improving treatment efficacy in neurological diseases.

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Section: Ischemic Strokementioning

confidence: 99%

The Role of Circadian Rhythm in Neurological Diseases: A Translational Perspective

2023

Aging dis

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Agomelatine promotes differentiation of oligodendrocyte precursor cells and preserves white matter integrity after cerebral ischemic stroke

Wang,

Li,

Kang

et al. 2024

J Cereb Blood Flow Metab

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White matter injury contributes to neurological disorders after acute ischemic stroke (AIS). The repair of white matter injury is dependent on the re-myelination by oligodendrocytes. Both melatonin and serotonin antagonist have been proved to protect against post-stroke white matter injury. Agomelatine (AGM) is a multi-functional treatment which is both a melatonin receptor agonist and selective serotonin receptor antagonist. Whether AGM protects against white matter injury after stroke and the underlying mechanisms remain elusive. Here, using the transient middle cerebral artery occlusion (tMCAO) model, we evaluated the therapeutic effects of AGM in stroke mice. Sensorimotor and cognitive functions, white matter integrity, oligodendroglial regeneration and re-myelination in stroke hemisphere after AGM treatment were analyzed. We found that AGM efficiently preserved white matter integrity, reduced brain tissue loss, attenuated long-term sensorimotor and cognitive deficits in tMCAO models. AGM treatment promoted OPC differentiation and enhanced re-myelination both in vitro, ex vivo and in vivo, although OPC proliferation was unaffected. Mechanistically, AGM activated low density lipoprotein receptor related protein 1 (LRP1), peroxisome proliferator-activated receptor γ (PPARγ) signaling thus promoted OPC differentiation and re-myelination after stroke. Inhibition of PPARγ or knock-down of LRP1 in OPCs reversed the beneficial effects of AGM. Altogether, our data indicate that AGM represents a novel therapy against white matter injury after cerebral ischemia.

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Melatonin Offers Dual-Phase Protection to Brain Vessel Endothelial Cells in Prolonged Cerebral Ischemia-Recanalization Through Ameliorating ER Stress and Resolving Refractory Stress Granule

Cited by 2 publications

References 52 publications

The Role of Circadian Rhythm in Neurological Diseases: A Translational Perspective

The Role of Circadian Rhythm in Neurological Diseases: A Translational Perspective

Agomelatine promotes differentiation of oligodendrocyte precursor cells and preserves white matter integrity after cerebral ischemic stroke

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