The pathophysiology of HIE is now better understood, and treatment with hypothermia has become the foundation of therapy. Several neuroprotective agents offer promise when combined with hypothermia and are entering clinical trials.

The mammalian gastrointestinal tract harbors a highly diverse microbial population that plays a major role in nutrition, metabolism, protection against pathogens, and development of the immune system. It is estimated that at least 1000 different bacterial species cohabit the human intestinal tract. Most recently, the Human Microbiome Project, using new genomic technologies, has started a catalog of specific microbiome composition and its correlation with health and specific diseases. Herein we provide a brief review of the intestinal microbiome, with a focus on new studies showing that there is an important link between the microbes that inhabit the intestinal tract and the developing brain. With future research, an understanding of this link may help us to treat various neurobehavioral problems such as autism, schizophrenia, and anxiety.

Lactobacillus rhamnosus GG (LGG), a probiotics, ameliorates intestinal and other organ inflammation in infant rats. The hypothesis is that live and heat-killed LGG have similar effects on decreasing the inflammatory response induced by E. coli lipopolysaccharide (LPS) in the infant rat. Using a gastrostomy-fed rat model, 7-d-old rat pups were gastrostomy fed with or without live LGG (10 8 or 10In a separate experiment, LPS was administered to rat pups with or without live or heat-killed LGG (10. Cytokine/chemokine proteins were determined by ELISA or multiplex assay. Both live and heat-killed LGG decreased LPS-induced cytokine-induced neutrophil chemoattractant-1 (CINC-1) production in liver and plasma (p Ͻ 0.05) and also showed a trend (p ϭ 0.09) in lungs. Live and heat-killed LGG ameliorated LPS-suppressed IL-10 level in lungs (p Ͻ 0.05). Both forms of LGG decreased IL-1b production in liver. There was no difference between low and high doses of live LGG in the production of CINC-1, TNF-␣, and myeloperoxidase (MPO). There was a trend of increase of claudin-1 in both live and heat-killed groups (p ϭ 0.08). In conclusion, both live and heat-killed LGG provided by the enteral route decrease LPS-induced proinflammatory mediators and increase anti-inflammatory mediators.

As neonatal intensive care has evolved, the focus has shifted from improving mortality alone to an effort to improve both mortality and morbidity. The most frequent source of neonatal brain injury occurs as a result of hypoxic-ischemic injury. Hypoxic-ischemic injury occurs in about 2 of 1,000 full-term infants and severe injured infants will have lifetime disabilities and neurodevelopmental delays. Most recently, remarkable efforts toward neuroprotection have been started with the advent of therapeutic hypothermia and a key step in the evolution of neonatal neuroprotection is the discovery of biomarkers that enable the clinician-scientist to screen infants for brain injury, monitor progression of disease, identify injured brain regions, and assess efficacy of neuroprotective clinical trials. Lastly, biomarkers offer great hope identifying when an injury occurred shedding light on the potential pathophysiology and the most effective therapy. In this article, we will review biomarkers of HIE including S100B, neuron specific enolase, umbilical cord IL-6, CK-BB, GFAP, myelin basic protein, UCHL-1, and pNF-H. We hope to contribute to the awareness, validation, and clinical use of established as well as novel neonatal brain injury biomarkers.

During the course of mammalian evolution, there has been a close relationship between microbes residing in the gastrointestinal (GI) tract and the mammalian host. Although the host provides the microbes with a warm environment and nutrients, they, in turn, undergo various metabolic processes that aid the host. The host has developed weapons against microbes that are considered foreign, as well as mechanisms to tolerate and live synergistically with most of the microbes in the GI tract. This relationship is proving to be important not only in the neonatal period and during infancy, but it is becoming increasingly evident that microbial colonization in early life may affect the individual's health throughout life. Here we will review this relationship in terms of health and disease, with a focus on the aspects of this relationship during maturation of the host.

Severe hypoxic-ischemic encephalopathy (HIE) is a devastating condition that can lead to mortality and long-term disabilities in term newborns. No rapid and reliable laboratory test exists to assess the degree of neuronal injury in these patients. We propose two possible biomarkers: 1) phosphorylated axonal neurofilament heavy chain (pNF-H) protein, one of the major subunits of neurofilaments, found only in axonal cytoskeleton of neurons and 2) Ubiquitin C-terminal hydrolase 1 (UCHL1 protein) that is heavily and specifically concentrated in neuronal perikarya and dendrites. High-serum pNF-H and UCHL1 levels are reported in subarachnoid hemorrhage and traumatic brain injury, suggesting that they are released into blood following neuronal injury. We hypothesized that serum pNF-H and UCHL1 were higher in neonates with moderate-to-severe HIE than in healthy neonates. A time-limited enrollment of 14 consecutive patients with HIE and 14 healthy controls was performed. UCHL1 and pNF-H were correlated with clinical data and brain MRI. UCHL1 and pNF-H serum levels were higher in HIE versus controls. UCHL1 showed correlation with the 10-min Apgar score, and pNF-H showed correlation with abnormal brain MRI. Our findings suggest that serum UCHL1 and pNF-H could be explored as diagnostic and prognostic tools in neonatal HIE.

The term “encephalopathy of prematurity” encompasses not only the acute brain injury [such as intraventricular hemorrhage (IVH)] but also complex disturbance on the infant’s subsequent brain development. In premature infants, the most frequent recognized source of brain injury is IVH and periventricular leukomalacia (PVL). Furthermore 20–25% infants with birth weigh less than 1,500 g will have IVH and that proportion increases to 45% if the birth weight is less than 500–750 g. In addition, nearly 60% of very low birth weight newborns will have hypoxic-ischemic injury. Therefore permanent lifetime neurodevelopmental disabilities are frequent in premature infants. Innovative approach to prevent or decrease brain injury in preterm infants requires discovery of biomarkers able to discriminate infants at risk for injury, monitor the progression of the injury, and assess efficacy of neuroprotective clinical trials. In this article, we will review biomarkers studied in premature infants with IVH, Post-hemorrhagic ventricular dilation (PHVD), and PVL including: S100b, Activin A, erythropoietin, chemokine CCL 18, GFAP, and NFL will also be examined. Some of the most promising biomarkers for IVH are S100β and Activin. The concentrations of TGF-β1, MMP-9, and PAI-1 in cerebrospinal fluid could be used to discriminate patients that will require shunt after PHVD. Neonatal brain injury is frequent in premature infants admitted to the neonatal intensive care and we hope to contribute to the awareness and interest in clinical validation of established as well as novel neonatal brain injury biomarkers.

Oral NaB given during the preweaning period did not significantly decrease the subsequent development of death from diabetes in biobreeding diabetes-prone rats.