ABSTRACT
BACKGROUND: Current diagnostic criteria for hypoxic-ischemic encephalopathy in the early hours lack objective measurement tools. Therefore, this systematic review aims to identify putative molecules that can be used in diagnosis in daily clinical practice (PROSPERO ID: CRD42021272610). DATA SOURCES: Searches were performed in PubMed, Web of Science, and Science Direct databases until November 2020. English original papers analyzing samples from newborns > 36 weeks that met at least two American College of Obstetricians and Gynecologists diagnostic criteria and/or imaging evidence of cerebral damage were included. Bias was assessed by the Newcastle-Ottawa Scale. The search and data extraction were verified by two authors separately. RESULTS: From 373 papers, 30 met the inclusion criteria. Data from samples collected in the first 72 hours were extracted, and increased serum levels of neuron-specific enolase and S100-calcium-binding protein-B were associated with a worse prognosis in newborns that suffered an episode of perinatal asphyxia. In addition, the levels of glial fibrillary acidic protein, ubiquitin carboxyl terminal hydrolase isozyme-L1, glutamic pyruvic transaminase-2, lactate, and glucose were elevated in newborns diagnosed with hypoxic-ischemic encephalopathy. Moreover, pathway analysis revealed insulin-like growth factor signaling and alanine, aspartate and glutamate metabolism to be involved in the early molecular response to insult. CONCLUSIONS: Neuron-specific enolase and S100-calcium-binding protein-B are potential biomarkers, since they are correlated with an unfavorable outcome of hypoxic-ischemic encephalopathy newborns. However, more studies are required to determine the sensitivity and specificity of this approach to be validated for clinical practice.
Subject(s)
Asphyxia Neonatorum , Hypoxia-Ischemia, Brain , Pregnancy , Female , Humans , Infant, Newborn , Hypoxia-Ischemia, Brain/diagnosis , Biomarkers , Prognosis , Asphyxia Neonatorum/complications , Asphyxia Neonatorum/diagnosis , S100 Proteins , Phosphopyruvate HydrataseABSTRACT
Neonatal hypoxic-ischemic encephalopathy (HIE) is an important cause of mortality and morbidity in the perinatal period. This condition results from a period of ischemia and hypoxia to the brain of neonates, leading to several disorders that profoundly affect the daily life of patients and their families. Currently, therapeutic hypothermia (TH) is the standard of care in developing countries; however, TH is not always effective, especially in severe cases of HIE. Addressing this concern, several preclinical studies assessed the potential of stem cell therapy (SCT) for HIE. With this systematic review, we gathered information included in 58 preclinical studies from the last decade, focusing on the ones using stem cells isolated from the umbilical cord blood, umbilical cord tissue, placenta, and bone marrow. Outstandingly, about 80% of these studies reported a significant improvement of cognitive and/or sensorimotor function, as well as decreased brain damage. These results show the potential of SCT for HIE and the possibility of this therapy, in combination with TH, becoming the next therapeutic approach for HIE. Nonetheless, few preclinical studies assessed the combination of TH and SCT for HIE, and the existent studies show some contradictory results, revealing the need to further explore this line of research.
Subject(s)
Brain Diseases/etiology , Brain Diseases/therapy , Cell- and Tissue-Based Therapy , Hypoxia-Ischemia, Brain/complications , Stem Cell Transplantation , Animals , Astrocytes , Brain Diseases/metabolism , Brain Diseases/pathology , Cell Differentiation , Cord Blood Stem Cell Transplantation , Disease Models, Animal , Humans , Hypothermia, Induced , Infant, Newborn , Mesenchymal Stem Cell Transplantation , Microglia , Neurogenesis , Neurons , Oxidative Stress , Standard of Care , Stem Cell Transplantation/methodsABSTRACT
In the clinical setting, a blood sample is typically the starting point for biomarker search and discovery. Mass spectrometry (MS) is a highly sensitive and informative method for characterizing a very wide range of metabolites and proteins and is therefore a potentially powerful tool for biomarker discovery. However, the physicochemical characteristics of blood coupled with very large ranges of protein and metabolite concentrations present a significant technical obstacle for resolving and quantifying putative biomarkers by MS. Blood fractionation procedures are being developed to reduce the proteome/metabolome complexity and concentration ranges, allowing a greater diversity of analytes, including those at very low concentrations, to be quantified. In this chapter, several strategies for enriching and/or isolating specific blood components are summarized, including methods for the analysis of low and high molecular weight compounds, usually neglected in this type of assays, extracellular vesicles, and peripheral blood mononuclear cells (PBMCs). For each method, relevant practical information is presented for effective implementation.
