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The Interplay Between Melatonin and Nitric Oxide: Mechanisms and Implications in Stroke Pathophysiology
Santos Blanco1, María Del Mar Muñoz-Gallardo1, Raquel Hernández1
1Department of Experimental Biology, University of Jaén, 23007 Jaén, Spain.
Antioxidants (Basel, Switzerland)
|June 26, 2025
Summary
Melatonin offers neuroprotection in stroke by favorably modulating the nitric oxide (NO) axis. It reduces harmful NO effects and inflammation, improving outcomes in stroke models.
Area of Science:
- Neuroscience
- Pharmacology
- Pathophysiology
Background:
- Melatonin is a neurohormone with antioxidant and anti-inflammatory properties.
- Nitric oxide (NO) plays a complex role in the central nervous system (CNS), influencing stroke pathophysiology.
- NO can be both neuroprotective and neurotoxic depending on its source and context.
Purpose of the Study:
- To review the intricate relationship between melatonin and NO in the CNS.
- To detail the involvement of the melatonin-NO axis in stroke pathophysiology.
- To highlight melatonin's therapeutic potential for ischemic stroke.
Main Methods:
- Review of existing literature on melatonin and nitric oxide in CNS and stroke.
- Analysis of melatonin's mechanisms of action related to NO signaling.
- Examination of preclinical data on melatonin's effects in stroke models.
Main Results:
- Melatonin demonstrates significant neuroprotective effects in animal models of ischemic stroke.
- Melatonin differentially modulates nitric oxide synthase (NOS) isoforms, suppressing detrimental iNOS and preserving eNOS.
- Melatonin scavenges NO and peroxynitrite, reduces neuroinflammation, and protects mitochondria.
Conclusions:
- Melatonin's favorable modulation of the melatonin-NO axis contributes to reduced infarct volume and improved functional outcomes in stroke.
- Melatonin exhibits considerable therapeutic potential for ischemic stroke.
- Targeting the melatonin-NO interaction is a promising strategy for stroke treatment.
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