The brain is highly susceptible to focal or global
ischemia. Unless
ischemia is promptly reversed, reperfusion produces further cerebral damage. Acute thrombolysis or defibrinogenation is effective only in selective patients with
ischemic stroke and carries a significant risk of
bleeding complications. Whereas numerous
neuroprotectants were shown to be effective in experimental studies, none of them have been shown to work in clinical trials. The major pathogenetic mechanisms of
ischemia/reperfusion injury include excitotoxicity, disturbed
calcium ion homeostasis, overproduction of
nitric oxide and other
free radicals,
inflammation, and apoptosis.
Nitric oxide and other
free radicals, the key mediators of excitotoxicity and disturbed
calcium ion homeostasis, cause direct injury and also indirectly damage via
inflammation and apoptosis.
Melatonin is a potent
free radical scavenger and an indirect
antioxidant. This mini review summarizes the in vivo and in vitro evidence that
melatonin protects against
ischemia/reperfusion injury. There is convincing evidence from the literature that
melatonin treatment is highly effective in different in vivo and in vitro models of excitotoxicity or
ischemia/reperfusion in multiple animal species.
Melatonin is safe and non-toxic in humans, and its administration via the oral route or
intravenous injection is convenient. While more experimental studies should be conducted to further explore the neuroprotective mechanisms and to document any synergistic or additive protection from combining
melatonin with thrombolysis, defibrinogenation or other
neuroprotectants, interested clinical scientists should consider planning phase II and III studies to confirm the benefit of
melatonin as an
acute stroke treatment or a preventive measure for
stroke patients.