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2.  Regionally Selective Atrophy after Traumatic Axonal Injury 
Archives of neurology  2010;67(11):1336-1344.
Objectives
To determine the spatial distribution of cortical and subcortical volume loss in patients with diffuse traumatic axonal injury and to assess the relationship between regional atrophy and functional outcome.
Design
Prospective imaging study. Longitudinal changes in global and regional brain volumes were assessed using high-resolution magnetic resonance imaging (MRI)-based morphometric analysis.
Setting
Inpatient traumatic brain injury unit
Patients or Other Participants
Twenty-five patients with diffuse traumatic axonal injury and 22 age- and sex-matched controls.
Main Outcome Measure
Changes in global and regional brain volumes between initial and follow-up MRI were used to assess the spatial distribution of post-traumatic volume loss. The Glasgow Outcome Scale – Extended was the primary measure of functional outcome.
Results
Patients underwent substantial global atrophy with mean brain parenchymal volume loss of 4.5% (95% Confidence Interval: 2.7 – 6.3%). Decreases in volume (at a false discovery rate of 0.05) were seen in several brain regions including the amygdala, hippocampus, thalamus, corpus callosum, putamen, precuneus, postcentral gyrus, paracentral lobule, and parietal and frontal cortices, while other regions such as the caudate and inferior temporal cortex were relatively resistant to atrophy. Loss of whole brain parenchymal volume was predictive of long-term disability, as was atrophy of particular brain regions including the inferior parietal cortex, pars orbitalis, pericalcarine cortex, and supramarginal gyrus.
Conclusion
Traumatic axonal injury leads to substantial post-traumatic atrophy that is regionally selective rather than diffuse, and volume loss in certain regions may have prognostic value for functional recovery.
doi:10.1001/archneurol.2010.149
PMCID: PMC3465162  PMID: 20625067
4.  Assessing Spatial Relationships between Axonal Integrity, Regional Brain Volumes, and Neuropsychological Outcomes after Traumatic Axonal Injury 
Journal of Neurotrauma  2010;27(12):2121-2130.
Abstract
Diffuse traumatic axonal injury (TAI) is a type of traumatic brain injury (TBI) characterized predominantly by white matter damage. While TAI is associated with cerebral atrophy, the relationship between gray matter volumes and TAI of afferent or efferent axonal pathways remains unknown. Moreover, it is unclear if deficits in cognition are associated with post-traumatic brain volumes in particular regions. The goal of this study was to determine the relationship between markers of TAI and volumes of cortical and subcortical structures, while also assessing the relationship between cognitive outcomes and regional brain volumes. High-resolution magnetic resonance imaging scans were performed in 24 patients with TAI within 1 week of injury and were repeated 8 months later. Diffusion tensor imaging (DTI) tractography was used to reconstruct prominent white matter tracts and calculate their fractional anisotropy (FA) and mean diffusivity (MD) values. Regional brain volumes were computed using semi-automated morphometric analysis. Pearson's correlation coefficients were used to assess associations between brain volumes, white matter integrity (i.e., FA and MD), and neuropsychological outcomes. Post-traumatic volumes of many gray matter structures were associated with chronic damage to related white matter tracts, and less strongly associated with measures of white matter integrity in the acute scans. For example, left and right hippocampal volumes correlated with FA in the fornix body (r = 0.600, p = 0.001; r = 0.714, p < 0.001, respectively). In addition, regional brain volumes were associated with deficits in corresponding neuropsychological domains. Our results suggest that TAI may be a primary mechanism of post-traumatic atrophy, and provide support for regional morphometry as a biomarker for cognitive outcome after injury.
doi:10.1089/neu.2010.1429
PMCID: PMC2996819  PMID: 20874032
atrophy; diffuse axonal injury; diffusion tensor imaging; traumatic brain injury; volumetric magnetic resonance imaging
5.  Maternal Substrate Utilization Programs the Development of the Metabolic Syndrome in Male Mice Exposed to High Fat in Utero 
Pediatric research  2009;66(4):368-373.
Studies were conducted to determine whether maternal substrate utilization during pregnancy affects fetal growth and predisposes offspring to metabolic disease. Female wild type (WT) and glucose transporter 4 heterozygous mice (G4+/−, a model of altered peripheral substrate utilization) were fed high fat (HFD, 36% fat) or control chow (C, 10% fat) for 2 weeks prior to mating, throughout pregnancy and lactation (IU/L). WT HFD females exhibited increased serum NEFA and lactate levels and increased hepatic mRNA expression of PGC1-β and SREBP-1c consistent with increased lipogenesis. G4+/− HFD females exhibited enhanced lipid clearance and exposure to HFD did not increase hepatic gene expression. HFD independent of maternal genotype decreased fetal growth, and birth weight. WT offspring were weaned onto a low-fat diet (5% fat). Male offspring of WT mothers exposed to HFD exhibited “catch-up” growth accompanied by increased adiposity, impaired glucose tolerance, and insulin sensitivity. In contrast, male offspring of G4+/− HFD mothers did not exhibit any characteristics of metabolic syndrome. These data suggest that differences in maternal substrate utilization influence offspring metabolic phenotype.
doi:10.1203/PDR.0b013e3181b33375
PMCID: PMC2795789  PMID: 19581843

Results 1-5 (5)