Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Feb 5:15:1356112.
doi: 10.3389/fphar.2024.1356112. eCollection 2024.

Systematic review of melatonin in cerebral ischemia-reperfusion injury: critical role and therapeutic opportunities

Chenguang Zhang #  1 , Yumei Ma #  1 , Yating Zhao  1 , Na Guo  1 , Chen Han  1 , Qian Wu  1 , Changqing Mu  1 , Yue Zhang  1 , Shutong Tan  1 , Jian Zhang  2   3 , Xu Liu  1
Affiliations
Review

Systematic review of melatonin in cerebral ischemia-reperfusion injury: critical role and therapeutic opportunities

Chenguang Zhang et al. Front Pharmacol. .

Abstract

Cerebral ischemia-reperfusion (I/R) injury is the predominant causes for the poor prognosis of ischemic stroke patients after reperfusion therapy. Currently, potent therapeutic interventions for cerebral I/R injury are still very limited. Melatonin, an endogenous hormone, was found to be valid in preventing I/R injury in a variety of organs. However, a systematic review covering all neuroprotective effects of melatonin in cerebral I/R injury has not been reported yet. Thus, we perform a comprehensive overview of the influence of melatonin on cerebral I/R injury by collecting all available literature exploring the latent effect of melatonin on cerebral I/R injury as well as ischemic stroke. In this systematic review, we outline the extensive scientific studies and summarize the beneficial functions of melatonin, including reducing infarct volume, decreasing brain edema, improving neurological functions and attenuating blood-brain barrier breakdown, as well as its key protective mechanisms on almost every aspect of cerebral I/R injury, including inhibiting oxidative stress, neuroinflammation, apoptosis, excessive autophagy, glutamate excitotoxicity and mitochondrial dysfunction. Subsequently, we also review the predictive and therapeutic implications of melatonin on ischemic stroke reported in clinical studies. We hope that our systematic review can provide the most comprehensive introduction of current advancements on melatonin in cerebral I/R injury and new insights into personalized diagnosis and treatment of ischemic stroke.

Keywords: cerebral ischemia-reperfusion injury; ischemic stroke; melatonin; neuroprotection; systematic review.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

FIGURE 1
FIGURE 1
Flow diagram of study identification and selection.
FIGURE 2
FIGURE 2
Protective mechanisms of melatonin in cerebral ischemia-reperfusion injury.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Ahmad A., Khan M. M., Ishrat T., Khan M. B., Khuwaja G., Raza S. S., et al. (2011). Synergistic effect of selenium and melatonin on neuroprotection in cerebral ischemia in rats. Biol. Trace Elem. Res. 139 (1), 81–96. 10.1007/s12011-010-8643-z - DOI - PubMed
    1. Akerstedt T., Froberg J. E., Friberg Y., Wetterberg L. (1979). Melatonin excretion, body temperature and subjective arousal during 64 hours of sleep deprivation. Psychoneuroendocrinology 4 (3), 219–225. 10.1016/0306-4530(79)90005-2 - DOI - PubMed
    1. Aly H., Elmahdy H., El-Dib M., Rowisha M., Awny M., El-Gohary T., et al. (2015). Melatonin use for neuroprotection in perinatal asphyxia: a randomized controlled pilot study. J. Perinatol. 35 (3), 186–191. 10.1038/jp.2014.186 - DOI - PubMed
    1. Anderson M. F., Sims N. R. (1999). Mitochondrial respiratory function and cell death in focal cerebral ischemia. J. Neurochem. 73 (3), 1189–1199. 10.1046/j.1471-4159.1999.0731189.x - DOI - PubMed
    1. Andrabi S. A., Sayeed I., Siemen D., Wolf G., Horn T. F. (2004). Direct inhibition of the mitochondrial permeability transition pore: a possible mechanism responsible for anti-apoptotic effects of melatonin. FASEB J. 18 (7), 869–871. 10.1096/fj.03-1031fje - DOI - PubMed

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (Grant No. 81400950), Natural Science Foundation of Liaoning Province (Grant No. 2019-MS-365).

LinkOut - more resources