Current models of chemotaxis during neuronal migration and axon guidance propose that directional sensing relies on growth cone dynamics. According to this view, migrating neurons and growing axons are guided to their correct targets by steering the growth cone in response to attractive and repulsive cues. Here, we have performed a detailed analysis of the dynamic behavior of individual neurons migrating tangentially in telencephalic slices using high-resolution time-lapse videomicroscopy. We found that cortical interneurons consistently display branched leading processes as part of their migratory cycle, a feature that seems to be common to many other populations of GABAergic neurons in the brain and spinal cord. Analysis of the migratory behavior of individual cells suggests that interneurons respond to chemoattractant signals by generating new leading process branches that are better aligned with the source of the gradient, and not by reorienting previously existing branches. Moreover, experimental evidence revealed that guidance cues influence the angle at which new branches emerge. This model is further supported by pharmacological experiments in which inhibition of branching blocked chemotaxis, suggesting that this process is an essential component of the mechanism controlling directional guidance. These results reveal a novel guidance mechanism during neuronal migration that might be extensively used in brain development.

Use of a new LHMF in preterm infants instead of powder HMF is safe. Benefits of LHMF include improvements in growth and avoidance of the use of powder products in the NICU.

Primary cultures of dorsal root ganglia cells from 18-to 21-day rodent embryos were studied for their ability to express Schwann cell function in a defined medium lacking serum and embryo extract. It was confirmed that Schwann cells, but not fibroblasts, are able to proliferate in response to contact with axons when cultured in this defined medium. We here report that in this medium, however, differentiation of Schwann cells was arrested before completion of ensheathment and before initiation of myelin formation. (13) to support proliferation of neuroblastoma cells; they observed neuronal growth and Schwann cell (but not fibroblast) proliferation in their dissociated cell cultures. In this paper, we report that, when this defined medium is used in our standard sensory ganglion preparations, Schwann cell proliferation occurs and differentiation is initiated but fails to progress to typical axonal ensheathment and myelination, even after many weeks in culture. Electron microscopic study of these cultures shows that secretory products of the neuron-related Schwann cells [basal lamina and collagen fibrils; (8)] are absent from the extracellular space. Ensheathment, appearance of basal lamina and fibrils, and myelination occur within several days, however, after serum and embryo extract are added to the defined medium. We will discuss the implication of these observations on the role of secretion in the expression of Schwann cell function. MATERIALS AND METHODSDRG were dissected from either rat or mouse 18-to 21-day embryos, and their connective tissue capsules were removed by using forceps (Dumont, modified) having exceptionally fine tips. Ganglia were used as explants or were dissociated by incubation at 370C for 30 min in 0.25% trypsin, followed by trituration with a pipette and filtration through a nylon membrane having 15-Mm pores. The ganglia or dissociated cells were plated on Aclar minidishes coated with reconstituted rat tail collagen and incubated as described (14). Explant cultures were established and maintained in either N2 medium alone or in N2 medium supplemented with serum, serum and embryo extract, or specific additions (Table 1). Dissociated cell cultures were initially plated in a starter (i.e., antimitotic) medium (AMM; see below) containing serum, embryo extract, and an antimitotic agent and designed to (i) promote vigorous initial axonal growth, (fi) permit optimal neuronal differentiation, and (ii) suppress the development of nonneuronal cells. Cell cultures were shifted to N2 medium 10-14 days later. Cultures were fed every 2-3 days with an appropriate medium. Compositions were as follows: the standard medium (SM) contained 65% Eagle's minimal essential medium (15), 25% human placental serum, 10% 9-day chicken embryo extract, glucose at 6 g/liter, and crude nerve growth factor (16) at :t50 biological units per ml; the AMM had the same basic composition as the SM, but also included 10 MtM uridine and fluorodeoxyuridine and had only 10% serum and 2% embryo extract; the N2 medium was pre...

We identified smaller total and regional cerebral tissue volumes in extremely low birth weight infants treated with relatively conservative regimens of dexamethasone. These volume deficits may be the structural antecedents of neuromotor and cognitive abnormalities reported after postnatal dexamethasone treatment.

Among infants between 1000 and 2000 g at birth, starting and advancing feedings at 30 mL/kg per day seems to be a safe practice and results in fewer days to reach full-volume feedings than using 20 mL/kg per day. This intervention also leads to faster weight gain and fewer days of intravenous fluids.

Newborn infants cared for in neonatal intensive care units may develop nosocomial infections. Cefepime, a "fourth-generation" cephalosporin (i.e., with activity against virtually all of the chromosomal-beta-lactamaseproducing and many extended-spectrum-beta-lactamase-producing organisms), provides excellent activity against many gram-negative pathogens resistant to expanded-spectrum cephalosporins currently used to treat neonatal infections. The purpose of this study was to determine the pharmacokinetics of cefepime in this population to optimize dosing and minimize potential adverse events. Premature and term infants <4 months of age hospitalized in two neonatal intensive care units were studied. Limited pharmacokinetic (PK) sampling occurred following a dose of cefepime at 50 mg/kg of body weight infused over 30 min. Population pharmacokinetic parameters were determined using the program NONMEM. Fifty-five infants were enrolled. Their average (؎ standard deviation) gestational age at birth was 30.5 ؎ 5.3 weeks, and their average postnatal age at PK evaluation was 14.5 ؎ 14.7 days. In the final PK model, cefepime clearance (CL) was strongly associated with serum creatinine (SCr) (CL [ml/min/kg] ‫؍‬ 0.26 ؉ 0.59/SCr). The volume of distribution for infants with a postconceptional age of <30 weeks was larger than that for infants with a postconceptional age of >30 weeks (0.51 versus 0.39 liter/kg, respectively). The Bayesian analysis-predicted cefepime trough concentration at a dose of 50 mg/kg every 12 h for infants <14 days of age was 29.9 ؎ 16.6 g/ml. Cefepime, dosed at 30 mg/kg/dose every 12 h for infants less than 14 days of age, regardless of gestational age, should provide antibiotic exposure equivalent to or greater than 50 mg/kg every 8 h in older infants and children.

The rapid morphologic changes in Schwann cells and in their relationships to axons during the transition from the premyelinating to the myelinating state have been known for more than 15 years. The sorting of axons by dividing Schwann cells, the establishment of a 1:1 relationship between a postmitotic Schwann cell, and the onset of myelin sheath formation have all been described in detail. However, the chain of molecular events and mechanisms by which these morphologic changes are regulated has not been elucidated. In this chapter we have reviewed results that strongly suggest that the adhesion molecule L1 is one of the important determinants that mediate the elongation of the Schwann cell along the axon, and the extension of Schwann processes to engulf axons. Thus, L1 functions to promote the spreading of the Schwann cell process over the surface of the axon. L1 does not appear to be exclusively involved in the adhesion of Schwann cells to axons, in the activation of Schwann cell proliferation by axons, or in the induction of synthesis of extracellular matrix proteins. The results from the anti-L1 blocking experiments further provided clues for an understanding of how the expression of GalC and MAG, which are both likely to be involved in the initiation of myelination, are regulated. These results imply that the overall regulation of expression of these early myelin components could require controls other than a single signaling mechanism derived from contact with axons. We propose that the deposition of basal lamina or one of its components could also be involved. Finally, the results from anti-GalC-blocking experiments indicated that GalC is involved in the mechanism of early growth of the myelin spiral.

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