Neuroglial metabolic compartmentation underlying leptin deficiency in the obese ob/ob mice as detected by magnetic resonance imaging and spectroscopy methods.

Manganese-Enhanced Magnetic Resonance Imaging (MEMRI), (1)H and (13)C High-Resolution-Magic Angle Spinning (HR-MAS) Spectroscopy, and genomic approaches were used to compare cerebral activation and neuronal and glial oxidative metabolism in ad libitum fed C57BL6/J leptin-deficient, genetically obese ob/ob mice. T(1)-weighted Magnetic Resonance Images across the hypothalamic Arcuate and the Ventromedial nuclei were acquired kinetically after manganese infusion. Neuroglial compartmentation was investigated in hypothalamic biopsies after intraperitoneal injections of [1-(13)C]glucose or [2-(13)C]acetate. Total RNA was extracted to determine the effects of leptin deficiency in the expression of representative genes coding for regulatory enzymes of hypothalamic energy pathways and glutamatergic neurotransmission. Manganese-Enhanced Magnetic Resonance Imaging revealed enhanced cerebral activation in the hypothalamic Arcuate and Ventromedial nuclei of the ob/ob mice. (13)C HR-MAS analysis showed increased (13)C accumulation in the hypothalamic glutamate and glutamine carbons of ob/ob mice after the administration of [1-(13)C]glucose, a primarily neuronal substrate. Hypothalamic expression of the genes coding for glucokinase, phosphofructokinase, pyruvate dehydrogenase, and glutamine synthase was not significantly altered while pyruvate kinase expression was slightly upregulated. In conclusion, leptin deficiency associated with obesity led to increased cerebral activation in the hypothalamic Arcuate and Ventromedial nuclei, concomitant with significant increases in neuronal oxidative metabolism and glutamatergic neurotransmission.

Brain region-selective mechanisms contribute to the progression of cerebral alterations in acute liver failure in rats.

BACKGROUND & AIMS: Patients with acute liver failure (ALF) often die of intracranial pressure (IP) and cerebral herniation. Main contributors to increased IP are ammonia, glutamine, edema, and blood flow. The sequence of events and underlying mechanisms, as well as the temporal pattern, regional distribution, and contribution of each parameter to the progression of neurologic deterioration and IP, are unclear. We studied rats with ALF to follow the progression of changes in ammonia, glutamine, grade and type (vasogenic or cytotoxic) of edema, blood-brain barrier permeability, cerebral blood flow, and IP. We assessed whether the changes in these parameters were similar between frontal cortex and cerebellum and evaluated the presence, type, and progression of edema in 12 brain areas. METHODS: ALF was induced by injection of galactosamine. The grade and type of edema was assessed by measuring the apparent diffusion coefficient by magnetic resonance imaging. Cerebral blood flow was measured by magnetic resonance and blood-brain barrier permeability by Evans blue-albumin extravasation. RESULTS: Increased IP arises from an early increase of blood-brain barrier permeability in certain areas (including cerebellum but not frontal cortex) followed by vasogenic edema. Ammonia and glutamine then increase progressively, leading to cytotoxic edema in many areas. Alterations in lactate and cerebral blood flow are later events that further increase IP. CONCLUSIONS: Different mechanisms in specific regions of the brain contribute, with different temporal patterns, to the progression of cerebral alterations and IP in ALF.

Cerebral activation by fasting induces lactate accumulation in the hypothalamus.

Carbon-13 ((13)C) high-resolution magic angle spinning (HR-MAS) spectroscopy was used to investigate the neuroglial coupling mechanisms underlying appetite regulation in the brain of C57BL/6J mice metabolizing [1-(13)C]glucose. Control fed or overnight fasted mice received [1-(13)C]glucose (20 micromol/g intraperitoneally [i.p.]), 15 min prior to brain fixation by focused microwaves. The hypothalamic region was dissected from the rest of the brain and (13)C HR-MAS spectra were obtained from both biopsies. Fasting resulted in a significant increase in hypothalamic [3-(13)C]lactate and [2-(13)C]gamma-aminobutyric acid (GABA) relative to the remaining brain. Administration of the orexigenic peptide ghrelin (0.3 nmol/g i.p.) did not increase hypothalamic [3-(13)C]lactate or [2-(13)C]GABA, suggesting that ghrelin signaling is not sufficient to elicit all the metabolic consequences of hypothalamic activation by fasting. Our results indicate that the hypothalamic regulation of appetite involves, in addition to the well-known neuropeptide signaling, increased neuroglial lactate shuttling and augmented GABA concentrations.

Volume mesh generation and finite element analysis of trabecular bone magnetic resonance images.

In order to help the assessment of trabecular bone diseases and complement Dual X-Ray Absorptiometry (DXA) in diagnosis process, it is needed an accurate mechanical characterization of trabecular bone structure to estimate the risk of fracture and evaluate micro-architecture deterioration. As Finite Element modeling has become a well-established method for analysis of complex structures, an algorithm has been developed to build a Finite Element mesh from three-dimensional reconstruction information in voxels. Generated mesh is loaded in a Finite Element analysis software in order to simulate micro-architecture mechanical behavior under compression conditions. Most part of related researches have been based on ex vivo micro-Computed Tomography (microCT) scans. This study uses three-dimensional trabecular bone reconstructions from high resolution Magnetic Resonance images acquired in vivo.

Clinical software for the assessment of trabecular bone disease in distal radius based on a magnetic resonance structural analysis.

As Bone Mineral Density has been demonstrated to be insufficient to elaborate a correct diagnosis of bone diseases such as osteoporosis, a new software tool called EsTra has been developed in order to estimate the most significant structural parameters of trabecular bone microarchitecture. In EsTra, different techniques as automated segmentation, snakes, filtering, skeletonization, voxel classification and three-dimensional reconstruction are applied to Magnetic Resonance images of distal radius and ulna. A microarchitectural study is also carried out from three different viewpoints involving morphological, topological and fractal analysis. Results can be exported to a database to help the research of the disease and a clinical report is elaborated containing the most significant parameters obtained from the analysis.