ArticleInternational journal of molecular medicine2018
Melatonin protects brain against ischemia/reperfusion injury by attenuating endoplasmic reticulum stress.
Article in International journal of molecular medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 88 citations in OpenAlex.
- Reactive oxygen species/hypoxia dual-responsive polymers combined with melatonin inhibited PANoptosis of retinal ganglion cells for acute glaucoma treatment.Theranostics · 2026Article
- Region-Dependent Responses to Oxygen-Glucose Deprivation and Melatonin in Neonatal Brain Organotypic Slices.Antioxidants (Basel, Switzerland) · 2025Article
- Melatonin Improves Neuroprotection and Neuroplasticity in Middle-Aged Mice Following Permanent Focal Cerebral Ischemia.Molecular neurobiology · 2025Article
- Ferroptosis and endoplasmic reticulum stress in ischemic stroke.Neural regeneration research · 2024Review
- Systematic review of melatonin in cerebral ischemia-reperfusion injury: critical role and therapeutic opportunities.Frontiers in pharmacology · 2024Review
- Melatonin Offers Dual-Phase Protection to Brain Vessel Endothelial Cells in Prolonged Cerebral Ischemia-Recanalization Through Ameliorating ER Stress and Resolving Refractory Stress Granule.Translational stroke research · 2023Article
- An Evaluation of the Effectiveness of Melatonin and n-Acetylcysteine in Cerebral Ischemia-Reperfusion Injury in Adult Rats.Medicina (Kaunas, Lithuania) · 2023Article
- Potential Neuroprotective Role of Melatonin in Sepsis-Associated Encephalopathy Due to Its Scavenging and Anti-Oxidative Properties.Antioxidants (Basel, Switzerland) · 2023Review
- Cerebral Glucose Metabolism and Potential Effects on Endoplasmic Reticulum Stress in Stroke.Aging and disease · 2023Review
- Melatonin Can Modulate Neurodegenerative Diseases by Regulating Endoplasmic Reticulum Stress.International journal of molecular sciences · 2023Review
- Inhibition of the Activating Transcription Factor 6 Branch of Endoplasmic Reticulum Stress Ameliorates Brain Injury after Deep Hypothermic Circulatory Arrest.Journal of clinical medicine · 2023Article
- Melatonin: a promising neuroprotective agent for cerebral ischemia-reperfusion injury.Frontiers in aging neuroscience · 2023Review
- The Role of Melatonin in Pregnancy and the Health Benefits for the Newborn.Biomedicines · 2022Review
- Sodium formononetin-3'-sulphonate alleviates cerebral ischemia-reperfusion injury in rats via suppressing endoplasmic reticulum stress-mediated apoptosis.BMC neuroscience · 2022Article
- The integrated stress response in ischemic diseases.Cell death and differentiation · 2022Review
- Subacute cadmium exposure modulates Th1 polarization to trigger ER stress-induced porcine hepatocyte apoptosis via regulation of miR-369-TNFα axis.Environmental science and pollution research international · 2022Article
- Protective effects of melatonin and L-carnitine against methotrexate-induced toxicity in isolated rat hepatocytes.Naunyn-Schmiedeberg's archives of pharmacology · 2022Article
- How cytosolic compartments play safeguard functions against neuroinflammation and cell death in cerebral ischemia.Metabolic brain disease · 2021Review
- Rosuvastatin protects PC12 cells from hypoxia/reoxygenation-induced injury by inhibiting endoplasmic reticulum stress-induced apoptosis.Experimental and therapeutic medicine · 2021Article
- Stroke-Induced Peripheral Immune Dysfunction in Vitamin D-Deficient Conditions: Modulation by Progesterone and Vitamin D.Molecular neurobiology · 2021Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endoplasmic reticulum (ER) stress plays a vital role in mediating ischemic reperfusion damage in brain. In this study, we evaluated whether melatonin inhibits ER stress in cultured neurons exposed to oxygen and glucose deprivation (OGD) and in rats subjected to transient focal cerebral ischemia. Sprague-Dawley rats were treated with melatonin (5 mg/kg) or control at reperfusion onset after transient occlusion of the right middle cerebral artery (MCA) for 90 min. Brain infarction and hemorrhage within infarcts were measured. The expression of ER stress proteins of phosphorylation of PRKR‑like endoplasmic reticulum kinase (p-PERK), phosphorylation of eukaryotic translation initiation factor 2α (p-eIF2α), activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP) were detected by western blotting and immunohistochemistry analysis. The terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) method, cleaved caspase-3 and cytochrome c were used to investigate cell apoptosis in OGD-induced cultured neurons. Our results demonstrated that animals treated with melatonin had significantly reduced infarction volumes and individual cortical lesion sizes as well as increased numbers of surviving neurons. Melatonin can significantly modulate protein levels by decreasing both p-PERK and p-eIF2α in the ischemic core and penumbra. Moreover, the expressions of ATF4 and CHOP were restrained in the ischemic core and penumbra, respectively. Furthermore, pretreatment with melatonin at 10-100 µM effectively reduced the levels of p-PERK and p-eIF2α in cultured neurons after OGD injury. Melatonin treatment also effectively decreased neuron apoptosis resulting from OGD-induced neuron injury. These results indicate that melatonin effectively attenuated post-ischemic ER stress after ischemic stroke.
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