Physiological and pharmacological roles of melatonin in the pathophysiological components of cellular injury after ischemic stroke

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Turkish Journal of Medical Sciences, vol.50, no.SI-2, pp.1655-1664, 2020 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Review
  • Volume: 50 Issue: SI-2
  • Publication Date: 2020
  • Doi Number: 10.3906/sag-2008-32
  • Journal Name: Turkish Journal of Medical Sciences
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database, TR DİZİN (ULAKBİM)
  • Page Numbers: pp.1655-1664
  • Keywords: Ischemic stroke, melatonin, free radicals, apoptosis, signaling, circadian rhythm proteins
  • Istanbul Medipol University Affiliated: Yes


Apart from its metabolic or physiological functions, melatonin has a potent cytoprotective activity in the physiological and pathological conditions. It is synthetized by the pineal gland and released into the blood circulation but particularly cerebrospinal fluid in a circadian manner. It can also easily diffuse through cellular membranes due its small size and lipophilic structure. Its cytoprotective activity has been linked to its potent free radical scavenger activity with the desirable characteristics of a clinically-reliable antioxidant. Melatonin detoxifies oxygen and nitrogen-based free radicals and oxidizing agents, including the highly toxic hydroxyl-and peroxynitrite radicals, initiating cellular damage. However, the cytoprotective activity of melatonin is complex and cannot be solely limited to its free radical scavenger activity. It regulates cellular signaling pathways through receptor– dependent and independent mechanisms. Most of these downstream molecules, such as PI3K/AKT pathway components, also contribute to the cytoprotective effects of melatonin. In this term, melatonin is a promising molecule for the treatment of neurodegenerative disorders, such as ischemic stroke, which melatonin reduces ischemic brain injury in animal models of ischemic stroke. It regulates also circadian rhythm proteins after ischemic stroke, playing roles in cellular survival. In this context, present article summarizes the possible role of melatonin in the pathophysiological events after ischemic stroke.