Cerebral activations during viewing of food stimuli in adult patients with acquired structural hypothalamic damage: A functional neuroimaging study

BACKGROUND/OBJECTIVES: Obesity is common following hypothalamic damage due to tumours. Homeostatic and non-homeostatic brain centres control appetite and energy balance but their interaction in the presence of hypothalamic damage remains unknown. We hypothesized that abnormal appetite in obese patients with hypothalamic damage results from aberrant brain processing of food stimuli. We sought to establish differences in activation of brain food motivation and reward neurocircuitry in patients with hypothalamic obesity (HO) compared with patients with hypothalamic damage whose weight had remained stable. SUBJECTS/METHODS: In a cross-sectional study at a University Clinical Research Centre, we studied 9 patients with HO, 10 age-matched obese controls, 7 patients who remained weight-stable following hypothalamic insult (HWS) and 10 non-obese controls. Functional magnetic resonance imaging was performed in the fasted state, 1 h and 3 h after a test meal, while subjects were presented with images of high-calorie foods, low-calorie foods and non-food objects. Insulin, glucagon-like peptide-1, Peptide YY and ghrelin were measured throughout the experiment, and appetite ratings were recorded. RESULTS: Mean neural activation in the posterior insula and lingual gyrus (brain areas linked to food motivation and reward value of food) in HWS were significantly lower than in the other three groups (P=0.001). A significant negative correlation was found between insulin levels and posterior insula activation (P=0.002). CONCLUSIONS: Neural pathways associated with food motivation and reward-related behaviour, and the influence of insulin on their activation may be involved in the pathophysiology of HO.International Journal of Obesity advance online publicatio

Childhood craniopharyngioma: greater hypothalamic involvement before surgery is associated with higher homeostasis model insulin resistance index

<p>Abstract</p> <p>Background</p> <p>Obesity seems to be linked to the hypothalamic involvement in craniopharyngioma. We evaluated the pre-surgery relationship between the degree of this involvement on magnetic resonance imaging and insulin resistance, as evaluated by the homeostasis model insulin resistance index (HOMA). As insulin-like growth factor 1, leptin, soluble leptin receptor (sOB-R) and ghrelin may also be involved, we compared their plasma concentrations and their link to weight change.</p> <p>Methods</p> <p>27 children with craniopharyngioma were classified as either grade 0 (n = 7, no hypothalamic involvement), grade 1 (n = 8, compression without involvement), or grade 2 (n = 12, severe involvement).</p> <p>Results</p> <p>Despite having similar body mass indexes (BMI), the grade 2 patients had higher glucose, insulin and HOMA before surgery than the grade 0 (P = 0.02, <0.05 and 0.02 respectively) and 1 patients (P < 0.02 and <0.03 for both insulin and HOMA). The grade 0 (5.8 ± 4.9) and 1 (7.2 ± 5.3) patients gained significantly less weight (kg) during the year after surgery than did the grade 2 (16.3 ± 7.4) patients. The pre-surgery HOMA was positively correlated with these weight changes (P < 0.03).</p> <p>The data for the whole population before and 6–18 months after surgery showed increases in BMI (P < 0.0001), insulin (P < 0.005), and leptin (P = 0.0005), and decreases in sOB-R (P < 0.04) and ghrelin (P < 0.03).</p> <p>Conclusion</p> <p>The hypothalamic involvement by the craniopharyngioma before surgery seems to determine the degree of insulin resistance, regardless of the BMI. The pre-surgery HOMA values were correlated with the post-surgery weight gain. This suggests that obesity should be prevented by reducing inn secretion in those cases with hypothalamic involvement.</p

Morphological and Behavioral Changes in the Pathogenesis of a Novel Mouse Model of Communicating Hydrocephalus

The Ro1 model of hydrocephalus represents an excellent model for studying the pathogenesis of hydrocephalus due to its complete penetrance and inducibility, enabling the investigation of the earliest cellular and histological changes in hydrocephalus prior to overt pathology. Hematoxylin and eosin staining, immunofluorescence and electron microscopy were used to characterize the histopathological events of hydrocephalus in this model. Additionally, a broad battery of behavioral tests was used to investigate behavioral changes in the Ro1 model of hydrocephalus. The earliest histological changes observed in this model were ventriculomegaly and disorganization of the ependymal lining of the aqueduct of Sylvius, which occurred concomitantly. Ventriculomegaly led to thinning of the ependyma, which was associated with periventricular edema and areas of the ventricular wall void of cilia and microvilli. Ependymal denudation was subsequent to severe ventriculomegaly, suggesting that it is an effect, rather than a cause, of hydrocephalus in the Ro1 model. Additionally, there was no closure of the aqueduct of Sylvius or any blockages within the ventricular system, even with severe ventriculomegaly, suggesting that the Ro1 model represents a model of communicating hydrocephalus. Interestingly, even with severe ventriculomegaly, there were no behavioral changes, suggesting that the brain is able to compensate for the structural changes that occur in the pathogenesis of hydrocephalus if the disorder progresses at a sufficiently slow rate

Precise Transit And Radial-Velocity Characterization Of A Resonant Pair: The Warm Jupiter TOI-216c And Eccentric Warm Neptune TOI-216b

TOI-216 hosts a pair of warm, large exoplanets discovered by the TESS mission. These planets were found to be in or near the 2:1 resonance, and both of them exhibit transit timing variations (TTVs). Precise characterization of the planets\u27 masses and radii, orbital properties, and resonant behavior can test theories for the origins of planets orbiting close to their stars. Previous characterization of the system using the first six sectors of TESS data suffered from a degeneracy between planet mass and orbital eccentricity. Radial-velocity measurements using HARPS, FEROS, and the Planet Finder Spectrograph break that degeneracy, and an expanded TTV baseline from TESS and an ongoing ground-based transit observing campaign increase the precision of the mass and eccentricity measurements. We determine that TOI-216c is a warm Jupiter, TOI-216b is an eccentric warm Neptune, and that they librate in 2:1 resonance with a moderate libration amplitude of ${60}_{-2}^{+2}$deg, a small but significant free eccentricity of ${0.0222}_{-0.0003}^{+0.0005}$for TOI-216b, and a small but significant mutual inclination of 1fdg2–3fdg9 (95% confidence interval). The libration amplitude, free eccentricity, and mutual inclination imply a disturbance of TOI-216b before or after resonance capture, perhaps by an undetected third planet

Reduction of astrogliosis and microgliosis by cerebrospinal fluid shunting in experimental hydrocephalus

<p>Abstract</p> <p>Background</p> <p>Reactive gliosis has the potential to alter biomechanical properties of the brain, impede neuronal regeneration and affect plasticity. Determining the onset and progression of reactive astrogliosis and microgliosis due to hydrocephalus is important for designing better clinical treatments.</p> <p>Methods</p> <p>Reactive astrogliosis and microgliosis were evaluated as the severity of hydrocephalus increased with age in hydrocephalic H-Tx rats and control littermates. Previous studies have suggested that gliosis may persist after short-term drainage (shunt treatment) of the cerebrospinal fluid. Therefore shunts were placed in 15d hydrocephalic rats that were sacrificed after 6d (21d of age) or after 21d (36d of age). Tissue was processed for Western blot procedures and immunohistochemistry, and probed for the astrocytic protein, Glial Fibrillary Acidic Protein (GFAP) and for microglial protein, Isolectin B4 (ILB4).</p> <p>Results</p> <p>In the parietal cortex of untreated hydrocephalic animals, GFAP levels increased significantly at 5d and at 12d compared to age-matched control rats. There was a continued increase in GFAP levels over control at 21d and at 36d. Shunting prevented some of the increase in GFAP levels in the parietal cortex. In the occipital cortex of untreated hydrocephalic animals, there was a significant increase over control in levels of GFAP at 5d. This trend continued in the 12d animals, although not significantly. Significant increases in GFAP levels were present in 21d and in 36d animals. Shunting significantly reduced GFAP levels in the 36d shunted group. Quantitative grading of immuno-stained sections showed similar changes in GFAP stained astrocytes.</p> <p>Immuno-stained microglia were altered in shape in hydrocephalic animals. At 5d and 12d, they appeared to be developmentally delayed with a lack of processes. Older 21d and 36d hydrocephalic animals exhibited the characteristics of activated microglia, with thicker processes and enlarged cell bodies. Following shunting, fewer activated microglia were present.</p> <p>Histologic examination of the periventricular area and the periaqueductal area showed similar findings with the 21d and 36d animals having increased populations of both astrocytes and microglia which were reduced following shunting with a more dramatic reduction in the long term shunted animals.</p> <p>Conclusion</p> <p>Overall, these results suggest that reactive astrocytosis and microgliosis are associated with progressive untreated ventriculomegaly, but that shunt treatment can reduce the gliosis occurring with hydrocephalus.</p

A review of the current treatment methods for posthaemorrhagic hydrocephalus of infants

Posthaemorrhagic hydrocephalus (PHH) is a major problem for premature infants, generally requiring lifelong care. It results from small blood clots inducing scarring within CSF channels impeding CSF circulation. Transforming growth factor – beta is released into CSF and cytokines stimulate deposition of extracellular matrix proteins which potentially obstruct CSF pathways. Prolonged raised pressures and free radical damage incur poor neurodevelopmental outcomes. The most common treatment involves permanent ventricular shunting with all its risks and consequences

Mesenchymal Transition and PDGFRA Amplification/Mutation Are Key Distinct Oncogenic Events in Pediatric Diffuse Intrinsic Pontine Gliomas

Diffuse intrinsic pontine glioma (DIPG) is one of the most frequent malignant pediatric brain tumor and its prognosis is universaly fatal. No significant improvement has been made in last thirty years over the standard treatment with radiotherapy. To address the paucity of understanding of DIPGs, we have carried out integrated molecular profiling of a large series of samples obtained with stereotactic biopsy at diagnosis. While chromosomal imbalances did not distinguish DIPG and supratentorial tumors on CGHarrays, gene expression profiling revealed clear differences between them, with brainstem gliomas resembling midline/thalamic tumours, indicating a closely-related origin. Two distinct subgroups of DIPG were identified. The first subgroup displayed mesenchymal and pro-angiogenic characteristics, with stem cell markers enrichment consistent with the possibility to grow tumor stem cells from these biopsies. The other subgroup displayed oligodendroglial features, and appeared largely driven by PDGFRA, in particular through amplification and/or novel missense mutations in the extracellular domain. Patients in this later group had a significantly worse outcome with an hazard ratio for early deaths, ie before 10 months, 8 fold greater that the ones in the other subgroup (p = 0.041, Cox regression model). The worse outcome of patients with the oligodendroglial type of tumors was confirmed on a series of 55 paraffin-embedded biopsy samples at diagnosis (median OS of 7.73 versus 12.37 months, p = 0.045, log-rank test). Two distinct transcriptional subclasses of DIPG with specific genomic alterations can be defined at diagnosis by oligodendroglial differentiation or mesenchymal transition, respectively. Classifying these tumors by signal transduction pathway activation and by mutation in pathway member genes may be particularily valuable for the development of targeted therapies

Benign external hydrocephalus: a review, with emphasis on management

Benign external hydrocephalus in infants, characterized by macrocephaly and typical neuroimaging findings, is considered as a self-limiting condition and is therefore rarely treated. This review concerns all aspects of this condition: etiology, neuroimaging, symptoms and clinical findings, treatment, and outcome, with emphasis on management. The review is based on a systematic search in the Pubmed and Web of Science databases. The search covered various forms of hydrocephalus, extracerebral fluid, and macrocephaly. Studies reporting small children with idiopathic external hydrocephalus were included, mostly focusing on the studies reporting a long-term outcome. A total of 147 studies are included, the majority however with a limited methodological quality. Several theories regarding pathophysiology and various symptoms, signs, and clinical findings underscore the heterogeneity of the condition. Neuroimaging is important in the differentiation between external hydrocephalus and similar conditions. A transient delay of psychomotor development is commonly seen during childhood. A long-term outcome is scarcely reported, and the results are varying. Although most children with external hydrocephalus seem to do well both initially and in the long term, a substantial number of patients show temporary or permanent psychomotor delay. To verify that this truly is a benign condition, we suggest that future research on external hydrocephalus should focus on the long-term effects of surgical treatment as opposed to conservative management

The Fifteenth Data Release of the Sloan Digital Sky Surveys: First Release of MaNGA-derived Quantities, Data Visualization Tools, and Stellar Library

Twenty years have passed since first light for the Sloan Digital Sky Survey (SDSS). Here, we release data taken by the fourth phase of SDSS (SDSS-IV) across its first three years of operation (2014 July–2017 July). This is the third data release for SDSS-IV, and the 15th from SDSS (Data Release Fifteen; DR15). New data come from MaNGA—we release 4824 data cubes, as well as the first stellar spectra in the MaNGA Stellar Library (MaStar), the first set of survey-supported analysis products (e.g., stellar and gas kinematics, emission-line and other maps) from the MaNGA Data Analysis Pipeline, and a new data visualization and access tool we call "Marvin." The next data release, DR16, will include new data from both APOGEE-2 and eBOSS; those surveys release no new data here, but we document updates and corrections to their data processing pipelines. The release is cumulative; it also includes the most recent reductions and calibrations of all data taken by SDSS since first light. In this paper, we describe the location and format of the data and tools and cite technical references describing how it was obtained and processed. The SDSS website (www.sdss.org) has also been updated, providing links to data downloads, tutorials, and examples of data use. Although SDSS-IV will continue to collect astronomical data until 2020, and will be followed by SDSS-V (2020–2025), we end this paper by describing plans to ensure the sustainability of the SDSS data archive for many years beyond the collection of data