Biomarkers of Hypoxic-Ischemic Encephalopathy in Newborns

Biomarkers are particles that are released from target organs during tissue hypoxia injury. Recognizing biomarkers released from the damaged brain helps physicians determine the extent of tissue damage and the use of protective techniques in clinical treatment. Previous studies revealed that biomarkers such as brain-specific proteins (neuron-specific enolase (NSE), S100B, ubiquitincarboxy-terminal hydrolase-L1, total Tau) and cytokines, including IL-6, IL-1β, IL-10, IL-13, interferon-gamma, TNF alpha and brain-derived neurotrophic factor are useful in diagnosing hypoxic-ischemic encephalopathy (HIE) and predicting nerve growth outcomes. However, optimal sensitivity and specificity of these biomarkers have not been achieved, which has limited their clinical application. This review focuses on biomarkers such as lactate, LDH, NRBC, NSE, S100B, GFAP, CPK-BB, IL-6, NPBI, UCHL-1. More sensitive and accurate instruments such as brain imaging (such as brain MRI), brain function (such as NIRS, aEEG), and long-term neuroassay should be used in the future to confirm biomarkers of neonatal brain damage.

Protective effects of melatonin on mitochondrial injury and neonatal neuron apoptosis induced by maternal hypothyroidism

In the current study, we reported the beneficial effects of melatonin in preventing neonatal neuronal apoptosis induced by maternal hypothyroidism. During the gestation and early lactation stages, the mother rats were given propylthiouracil (PTU) to inhibit their thyroid gland activity which resulted in the increased serum TSH and reduced T4 levels. This maternal hypothyroidism caused neuronal apoptosis of their pups, particularly in the CA3 area of hippocampus. Melatonin administration preserved function of thyroid gland and significantly reduced the apoptosis. Further studies have uncovered the potentially protective mechanisms of melatonin, that is, as a mitochondrial targeted antioxidant, melatonin preserves the mitochondrial outer membrane, inhibits the release of cytochrome C from mitochondria to cytoplasm and down regulates the gene expressions of Bax, along with caspases 3 and 9. Thus, melatonin breaks the mitochondria related apoptotic pathway to suppress the neuronal apoptosis induced by the maternal hypothyroidism. Considering the limited remedies to effectively treat hypothyroidism associated neonatal brain damage, melatonin may provide an alternative method for this disorder.

Use of Early Biomarkers in Neonatal Brain Damage and Sepsis: State of the Art and Future Perspectives

The identification of early noninvasive biochemical markers of disease is a crucial issue of the current scientific research, particularly during the first period of life, since it could provide useful and precocious diagnostic information when clinical and radiological signs are still silent. The ideal biomarker should be practical and sensitive in the precocious identification of at risk patients. An earlier diagnosis may lead to a larger therapeutic window and improve neonatal outcome. Brain damage and sepsis are common causes of severe morbidity with poor outcome and mortality during the perinatal period. A large number of potential biomarkers, including neuroproteins, calcium binding proteins, enzymes, oxidative stress markers, vasoactive agents, and inflammatory mediators, have been so far investigated. The aim of the present review was to provide a brief overview of some of the more commonly investigated biomarkers used in case of neonatal brain damage and sepsis.