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Biomedical subjects

Laura R Ment

Publications and source records attributed to Laura R Ment.

23 records · Page 2Linked to original sources

Regional brain volumes and their later neurodevelopmental correlates in term and preterm infants.

OBJECTIVE: To compare regional brain volumes measured in term and preterm infants, and to correlate regional volumes with measures of neurodevelopmental outcome. METHODS: High-contrast, high-resolution magnetic resonance imaging scans were acquired in 10 preterm and 14 term infants who were scanned near term. The cerebrum was segmented into cortical gray matter, white matter, cerebral ventricles, subcortical gray matter, cerebellum, and brainstem. The cortical gray matter, white matter, and ventricles were further divided into specific anatomic subregions, and the volumes were compared across groups. Measures of cognitive and motor development were acquired between 18 and 20 months of corrected age. Correlations of regional brain volumes with developmental outcome were assessed in the preterm group. RESULTS: Volumes in preterm infants were reduced in parieto-occipital gray matter and increased in the midbody, occipital horn, and temporal horns of the lateral ventricles. Gray matter volumes were also less prominently reduced in the sensorimotor and inferior occipital cortices. Normal lateralization of white matter volumes were altered in the parieto-occipital region in the preterm infants, who had significantly larger left-sided and smaller right-sided structures. White matter volumes in the sensorimotor and midtemporal regions correlated strongly with measures of neurodevelopmental outcome. CONCLUSIONS: These findings of reduced volumes in sensorimotor and parieto-occipital regions in preterm infants, and the prospective correlations of regional volumes with cognitive outcome, confirm and extend findings previously reported in a cross-sectional study of 8-year-old prematurely born children. The data suggest that regional brain volumes near term are a promising marker for predicting disturbances of cognitive outcome in preterm infants. Further prospective, longitudinal studies of neonatal brain volumes and developmental indices into later childhood are required to confirm the utility of regional brain volumes as predictors of longer term outcome.

Anatomy, Cross-Sectional↗

Disrupted synaptic development in the hypoxic newborn brain.

Infants born prematurely risk significant life-long cognitive disability, representing a major pediatric health crisis. The neuropathology of this cohort is accurately modeled in mice subjected to sublethal postnatal hypoxia. Massively parallel transcriptome analysis using cDNA microchips (9,262 genes), combined with immunohistochemical and protein assays, reveals that sublethal hypoxia accentuates genes subserving presynaptic function, and it suppresses genes involved with synaptic maturation, postsynaptic function, and neurotransmission. Other significantly affected pathways include those involved with glial maturation, vasculogenesis, and components of the cortical and microtubular cytoskeleton. These patterns reveal a global dysynchrony in the maturation programs of the hypoxic developing brain, and offer insights into the vulnerabilities of processes that guide early postnatal cerebral maturation.

Animals↗

Paracrine and autocrine functions of neuronal vascular endothelial growth factor (VEGF) in the central nervous system.

Recent data have demonstrated that vascular endothelial growth factor (VEGF) is expressed by subsets of neurons, coincident with angiogenesis within the developing cerebral cortex. Here we investigate the characteristics of VEGF expression by neurons and test the hypothesis that VEGF may serve both paracrine and autocrine functions in the developing central nervous system. To begin to address these questions, we assayed expression of VEGF and one of its potential receptors, Flk-1 (VEGFR-2), in the embryonic mouse forebrain and embryonic cortical neurons grown in vitro. Both VEGF and Flk-1 are present in subsets of post-mitotic neurons in vivo and in vitro. Moreover, VEGF levels are up-regulated in neuronal cultures subjected to hypoxia, consistent with our previous results in vivo. While the abundance of Flk-1 is unaffected by hypoxia, the receptor exhibits a higher level of tyrosine phosphorylation, as do downstream signaling kinases, including extracellular signal-regulated protein kinase, p90RSK and STAT3a, demonstrating activation of the VEGF pathway. These same signaling components also exhibited higher tyrosine phosphorylation levels in response to exogenous addition of rVEGFA(165). This activation was diminished in the presence of specific inhibitors of Flk-1 function and agents that sequester VEGF, resulting in a dose-dependent increase in apoptosis in these neuronal cultures. Further, inhibition of MEK resulted in increased apoptosis, while inhibition of phosphatidylinositol 3-kinase had no appreciable affect. In addition to the novel function for VEGF that we describe in neuronal survival, neuronal VEGF also affected the organization and differentiation of brain endothelial cells in a three-dimensional culture paradigm, consistent with its more traditional role as a vascular agent. Thus, our in vitro data support a role for neuronal VEGF in both paracrine and autocrine signaling in the maintenance of neurons and endothelia in the central nervous system.

Animals↗

A functional magnetic resonance imaging study of language processing and its cognitive correlates in prematurely born children.

OBJECTIVE: Abnormalities in brain structure, cognition, and behavior have been described in children born prematurely. However, no direct in vivo evidence has yet demonstrated abnormal neural processing in these children. Our aim was to compare brain activity associated with phonologic and semantic processing of language between term and preterm children using functional magnetic resonance imaging (fMRI). METHODS: fMRI scans were acquired during a passive language comprehension task in 26 preterm children at 8 years of age and in 13 term community control children who were comparable in age, sex, maternal education, and minority status. IQ was assessed using a standard measure of intelligence. RESULTS: The pattern of brain activity identified in a semantic processing task in the preterm children closely resembled the pattern of brain activity identified in a phonologic processing task in term controls. The greater this resemblance in the preterm children, the lower their verbal comprehension IQ scores and the poorer their language comprehension during the scanning task. CONCLUSIONS: Preterm children with the poorest language comprehension seemed not to fully engage normal semantic processing pathways in a language comprehension task. These children instead engaged pathways that normal term children used to process meaningless phonologic sounds. Aberrant processing of semantic content in these preterm children may account in part for their lower verbal IQ scores.

Benzophenones↗