Brain Damage in Preterm and Full-Term Neonates: Serum Biomarkers for the Early Diagnosis and Intervention

Abstract

The Brain is vulnerable to numerous insults that can act in the pre-, peri-, and post-natal period. There is growing evidence that demonstrate how oxidative stress (OS) could represent the final common pathway of all these insults. Fetuses and newborns are particularly vulnerable to OS due to their inability to active the antioxidant defenses. Specific molecules involved in OS could be measured in biologic fluids as early biomarkers of neonatal brain injury with an essential role in neuroprotection. Although S-100B seems to be the most studied biomarker, its use in clinical practice is limited by the complexity of brain damage etiopathogenesis and the time of blood sampling in relation to the brain injury. Reliable early specific serum markers are currently lacking in clinical practice. It is essential to determine if there are specific biomarkers that can help caregivers to monitor the progression of the disease in order to active an early neuroprotective strategy. We aimed to describe, in an educational review, the actual evidence on serum biomarkers for the early identification of newborns at a high risk of neurological diseases. To move the biomarkers from the bench to the bedside, the assays must be not only be of a high sensitivity but suitable for the very rapid processing and return of the results for the clinical practice to act on. For the best prognosis, more studies should focus on the association of these biomarkers to the type and severity of perinatal brain damage.

Designed Directional Growth of Ti-Metal–Organic Frameworks for Decoding Alzheimer’s Disease-Specific Exosome Metabolites

“…Experiments showed that tyrosine supplementation could increase dopamine levels to prevent age-related cognitive decline; dopaminergic function was a therapeutic strategy in AD. , The catecholamines were reported to have the potential to mitigate Aβ-triggered oxidative stress and inflammation by reducing the induction of inflammatory mediators during neurofibrillary tangle formation and early “preplaque” stages in AD progression. , Butyrylcarnitine ( m / z = 232.07, HMDB0002013) is a causal mediator of psychiatric disorders and has adverse effects when accumulated in blood . The reduction of butyrylcarnitine was correlated with cognitive improvement in AD, depressive symptomology, and schizophrenia. , Some reports found a positive association between butyrylcarnitine and neuron-specific enolase, regarding it as a potential prognostic biomarker for neuronal insult and psychiatric disorder …”

“…49,50 Some reports found a positive association between butyrylcarnitine and neuron-specific enolase, regarding it as a potential prognostic biomarker for neuronal insult and psychiatric disorder. 51 Afterward, we defined the three metabolites as a metabolic diagnostic panel toward clinical use of AD. Remarkably, based on the metabolic diagnostic panel, we achieved 100% accuracy, 100% sensitivity, and 100% specificity in identifying AD subjects through training on samples from the training set (R 2 Y = 0.910, Q 2 = 0.907), thereby building a robust OPLS-DA model (Figure S11).…”

Effects of Neonatal Hypoxic-Ischemic Injury on Brain Sterol Synthesis and Metabolism

“…Although brain sterol targeting might not hold the key to improving outcomes in this population, several other alternative therapies are currently being investigated and have shown some early promise for providing neuroprotective benefits. 32,33 Further studies to unveil underlying mechanism as well as to evaluate sterol changes within the context of more multivariable assessments with several different biomarkers combined to produce a single model (e.g., Perrone et al 34 ) may be beneficial.…”

Treatment of preterm brain injury via gut‐microbiota–metabolite–brain axis

“…15,16 Prenatal or postnatal factors (such as intrauterine infection and/ or inflammation, fetal immune response syndrome, and hypoxiaischemia) may affect the pathophysiology of preterm brain injury and is related to adverse neurological outcomes. 17 These factors may trigger oxidative stress reaction to produce a large number of oxygen free radicals (FRs). Because the brain of preterm infants cannot activate antioxidant defense, it is particularly vulnerable to OS damage and sensitive to FRs, which causes neuronal degeneration, edema, death, and can lead to cerebral palsy, cognitive, behavioral, and attention deficits.…”

“…Prenatal or postnatal factors (such as intrauterine infection and/or inflammation, fetal immune response syndrome, and hypoxia–ischemia) may affect the pathophysiology of preterm brain injury and is related to adverse neurological outcomes 17 . These factors may trigger oxidative stress reaction to produce a large number of oxygen free radicals (FRs).…”