Neuroprotective Effect of Melatonin: A Novel Therapy against Perinatal Hypoxia-Ischemia

Abstract

One of the most common causes of mortality and morbidity in children is perinatal hypoxia-ischemia (HI). In spite of the advances in neonatology, its incidence is not diminishing, generating a pediatric population that will require an extended amount of chronic care throughout their lifetime. For this reason, new and more effective neuroprotective strategies are urgently required, in order to minimize as much as possible the neurological consequences of this encephalopathy. In this sense, interest has grown in the neuroprotective possibilities of melatonin, as this hormone may help to maintain cell survival through the modulation of a wide range of physiological functions. Although some of the mechanisms by which melatonin is neuroprotective after neonatal asphyxia remain a subject of investigation, this review tries to summarize some of the most recent advances related with its use as a therapeutic drug against perinatal hypoxic-ischemic brain injury, supporting the high interest in this indoleamine as a future feasible strategy for cerebral asphyctic events.

Effect of Melatonin and Resveratrol against Memory Impairment and Hippocampal Damage in a Rat Model of Vascular Dementia

“…It has been well-documented, as discussed above, that melatonin and resveratrol both exert neuroprotective activity against cognitive deficits via the inhibition of elevated proinflammatory cytokines. It has been shown that melatonin and resveratrol inhibit NF-κB activation and restrain microglia activation, which further reduces the production of proinflammatory cytokines [63][64][65] . In our study, we found that melatonin and resveratrol inhibited the elevated proinflammatory cytokines in the hippocampus of BCCAO-treated rats.…”

Effects of Antenatal Melatonin Treatment on the Cerebral Vasculature in an Ovine Model of Fetal Growth Restriction

“…We queried whether this effect was mediated via the antiapoptotic actions of MLT as documented under other pathophysiological conditions. MLT is shown to prevent cytochrome c release, reduce or inhibit caspase-1 and caspase-3 activation, and increase the expression of the antiapoptotic proteins Bcl-2 and Bcl-xL [51,52] . In sheep, MLT attenuates cell death in the fetal brain following intrauterine asphyxia mid-gestation [9] and at full term [6] .…”

Melatonin use for neuroprotection in perinatal asphyxia: a randomized controlled pilot study

“…19 Finally, melatonin not only has significant anti-apoptotic activity which mainly targets the mitochondria, but also enhances several cell rescue pathways. 12 Melatonin is an attractive agent for neuroprotection as it freely crosses the placenta and the blood-brain barrier. It protects the brain of asphyxiated animals when used alone 20 or in combination with therapeutic hypothermia.…”

“…11 Melatonin has antioxidant, anti-inflammatory and antiapoptotic properties. 12 As an antioxidant, it directly neutralizes reactive oxygen species and reactive nitrogen species including nitric oxide (NO). It also acts indirectly by stimulating both antioxidant enzyme activity and their cellular mRNA concentrations, including superoxide dismutase (SOD), glutathione peroxidase and glutathione reductase.…”