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Melatonin in Hypoxic-Ischemic Brain Injury in Term and Preterm Babies.

ABSTRACT: Melatonin may serve as a potential therapeutic free radical scavenger and broad-spectrum antioxidant. It shows neuroprotective properties against hypoxic-ischemic brain injury in animal models. The authors review the studies focusing on the neuroprotective potential of melatonin and its possibility of treatment after perinatal asphyxia. Melatonin efficacy, low toxicity, and ability to readily cross through the blood-brain barrier make it a promising molecule. A very interesting thing is the difference between the half-life of melatonin in preterm neonates (15 hours) and adults (45-60 minutes). Probably, the use of synergic strategies-hypothermia coupled with melatonin treatment-may be promising in improving antioxidant action. The authors discuss and try to summarize the evidence surrounding the use of melatonin in hypoxic-ischemic events in term and preterm babies.

SUBMITTER: Paprocka J

PROVIDER: S-EPMC6402213 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Melatonin in Hypoxic-Ischemic Brain Injury in Term and Preterm Babies.

Paprocka Justyna J Kijonka Marek M Rzepka Beata B Sokół Maria M

International journal of endocrinology 20190220

Melatonin may serve as a potential therapeutic free radical scavenger and broad-spectrum antioxidant. It shows neuroprotective properties against hypoxic-ischemic brain injury in animal models. The authors review the studies focusing on the neuroprotective potential of melatonin and its possibility of treatment after perinatal asphyxia. Melatonin efficacy, low toxicity, and ability to readily cross through the blood-brain barrier make it a promising molecule. A very interesting thing is the diff ...[more]

PMID: 30915118

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Project description:Hypoxic-ischemic encephalopathy (HIE) is a major cause of mortality and morbidity in neonates, with an estimated global incidence of 3/1,000 live births. HIE brain damage is associated with an inflammatory response and oxidative stress, resulting in the activation of cell death pathways. At present, therapeutic hypothermia is the only clinically approved treatment available for HIE. This approach, however, is only partially effective. Therefore, there is an unmet clinical need for the development of novel therapeutic interventions for the treatment of HIE. Curcumin is an antioxidant reactive oxygen species scavenger, with reported anti-tumor and anti-inflammatory activity. Curcumin has been shown to attenuate mitochondrial dysfunction, stabilize the cell membrane, stimulate proliferation, and reduce injury severity in adult models of spinal cord injury, cancer, and cardiovascular disease. The role of curcumin in neonatal HIE has not been widely studied due to its low bioavailability and limited aqueous solubility. The aim of this study was to investigate the effect of curcumin treatment in neonatal HIE, including time of administration and dose-dependent effects. Our results indicate that curcumin administration prior to HIE in neonatal mice elevated cell and tissue loss, as well as glial activation compared to HI alone. However, immediate post-treatment with curcumin was significantly neuroprotective, reducing grey and white matter tissue loss, TUNEL+ cell death, microglia activation, reactive astrogliosis, and iNOS oxidative stress when compared to vehicle-treated littermates. This effect was dose-dependent, with 200 μg/g body weight as the optimal dose-regimen, and was maintained when curcumin treatment was delayed by 60 or 120 min post-HI. Cell proliferation measurements showed no changes between curcumin and HI alone, suggesting that the protective effects of curcumin on the neonatal brain following HI are most likely due to curcumin's anti-inflammatory and antioxidant properties, as seen in the reduced glial and iNOS activity. In conclusion, this study suggests curcumin as a potent neuroprotective agent with potential for the treatment of HIE. The delayed application of curcumin further increases its clinical relevance.

Dataset Information

Melatonin in Hypoxic-Ischemic Brain Injury in Term and Preterm Babies.

Publications

Melatonin in Hypoxic-Ischemic Brain Injury in Term and Preterm Babies.

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