ArticleCellular and molecular neurobiology2022
Modulation of α7nAchR by Melatonin Alleviates Ischemia and Reperfusion-Compromised Integrity of Blood-Brain Barrier Through Inhibiting HMGB1-Mediated Microglia Activation and CRTC1-Mediated Neuronal Loss.
Article in Cellular and molecular neurobiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Review
- Neuroglia and immune cells play different roles in neuroinflammation and neuroimmune response in post-stroke neural injury and repair.Acta pharmacologica Sinica · 2026Review
- Nociceptor α7nAChR activation blunts neuronal HMGB1 release and attenuates inflammation and nociceptive behavior.Molecular medicine (Cambridge, Mass.) · 2025Article
- Protective effects of melatonin on stroke in diabetic mice: central and peripheral inflammation modulation.Stroke and vascular neurology · 2025Article
- Melatonin inhibits the activation of microglia and cough sensitivity of guinea pigs exposed to PM2.5.Histology and histopathology · 2025Article
- Aging-Induced Episodic-Like Memory Impairment Could be Alleviated by Melatonin Treatment via Preserving Blood-Brain Barrier Integrity and Upregulating CRTC1.CNS neuroscience & therapeutics · 2025Article
- Mechanism of USP18-Mediated NCOA4 m6A Modification Via Maintaining FTO Stability In Regulating Ferritinophagy-Mediated Ferroptosis in Cerebral Ischemia-Reperfusion Injury.Molecular neurobiology · 2025Article
- Glial growth factor 2 treatment alleviates ischemia and reperfusion-damaged integrity of the blood-brain barrier through decreasing Mfsd2a/caveolin-1-mediated transcellular and Pdlim5/YAP/TAZ-mediated paracellular permeability.Acta pharmacologica Sinica · 2024Article
- Programmed cell death and melatonin: A comprehensive review.Functional & integrative genomics · 2024Review
- Nicotine Treatment Ameliorates Blood-Brain Barrier Damage After Acute Ischemic Stroke by Regulating Endothelial Scaffolding Protein Pdlim5.Translational stroke research · 2024Article
- Hypochlorous acid derived from microglial myeloperoxidase could mediate high-mobility group box 1 release from neurons to amplify brain damage in cerebral ischemia-reperfusion injury.Journal of neuroinflammation · 2024Article
- Non-neuronal cholinergic system in the heart influences its homeostasis and an extra-cardiac site, the blood-brain barrier.Frontiers in cardiovascular medicine · 2024Review
- N-acetylserotonin alleviates retinal ischemia-reperfusion injuryInternational journal of ophthalmology · 2024Article
- Systematic review of melatonin in cerebral ischemia-reperfusion injury: critical role and therapeutic opportunities.Frontiers in pharmacology · 2024Review
- Microglia at the blood brain barrier in health and disease.Frontiers in cellular neuroscience · 2024Review
- Neuronal Zinc Transporter ZnT3 Modulates Cerebral Ischemia-Induced Blood-Brain Barrier Disruption.Aging and disease · 2023Article
- Role of Crosstalk between Glial Cells and Immune Cells in Blood-Brain Barrier Damage and Protection after Acute Ischemic Stroke.Aging and disease · 2023Review
- Potential Neuroprotective Role of Melatonin in Sepsis-Associated Encephalopathy Due to Its Scavenging and Anti-Oxidative Properties.Antioxidants (Basel, Switzerland) · 2023Review
- CRTC1 is a potential target to delay aging-induced cognitive deficit by protecting the integrity of the blood-brain barrier via inhibiting inflammation.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Review
- Nicotine pretreatment alleviates MK-801-induced behavioral and cognitive deficits in mice by regulating Pdlim5/CRTC1 in the PFC.Acta pharmacologica Sinica · 2023Article
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
The only food and drug administration (FDA)-approved drug currently available for the treatment of acute ischemic stroke is tissue plasminogen activator (tPA), yet the therapeutic benefits of this drug are partially outweighed by the increased risk of hemorrhagic transformation (HT). Analysis of the NIH trial has shown that cigarette smoking protected tPA-treated patients from HT; however, the underlying mechanism is not clear. Nicotinic acetylcholine receptors (nAChR) has shown anti-inflammatory effect and modulation nAChR could be a strategy to reduce ischemia/reperfusion-induced blood-brain barrier (BBB) damage. Since melatonin could regulate the expression of α7nAchR and melatonin's neuroprotective effect against ischemic injury is mediated via α7nAChR modulation, here, we aim to test the hypothesis that melatonin reduces ischemia and reperfusion (I/R)-induced BBB damage through modulation of α7nACh receptor (α7nAChR). Mice were subjected to 1.5 h ischemia and 24 h reperfusion and at the onset of reperfusion, mice received intraperitoneal administration (i.p.) of either drug or saline. Mice were randomly assigned into five groups: Saline; α7nAChR agonist PNU282987; Melatonin; Melatonin+Methyllycaconitine (MLA, α7nAChR antagonist), and MLA group. BBB permeability was assessed by detecting the extravasation of Evan's blue and IgG. Our results showed that I/R significantly increased BBB permeability accompanied by occludin degradation, microglia activation, and high mobility group box 1 (HMGB1) release from the neuron. In addition, I/R significantly induced neuronal loss accompanied by the decrease of CREB-regulated transcriptional coactivator 1 (CRTC1) and p-CREB expression. Melatonin treatment significantly inhibited the above changes through modulating α7nAChR. Taken together, these results demonstrate that melatonin provides a protective effect on ischemia/reperfusion-induced BBB damage, at least in part, depending on the modulation of α7nAChR.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.