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Ellen A Schur - One of the best experts on this subject based on the ideXlab platform.

  • pilot multi site and reproducibility study of hypothalamic Gliosis in children
    Pediatric Obesity, 2020
    Co-Authors: Leticia Esposito Sewaybricker, Susan J Melhorn, Mary F. Webb, Afroditi Papantoni, Jun Hua, Christian L Roth, Susan Carnell, Ellen A Schur
    Abstract:

    OBJECTIVE Quantitative magnetic resonance imaging (MRI) evidence of mediobasal hypothalamic (MBH) Gliosis positively correlates with body mass index (BMI) in adults. This has neither been well explored in children nor have other brain regions involved in appetitive processing been tested for evidence of Gliosis. METHODS Multi-site cross-sectional study in children to test for differences in quantitative T2 signal (measure of Gliosis) by region and to assess relationships with age and BMI. Participants underwent brain MRI using the same equipment and protocol to quantify T2 relaxation time in six bilateral regions of interest (ROIs): putamen, caudate, ventral striatum, amygdala, hippocampus and MBH, and three control regions: white matter, motor cortex and dorsal hypothalamus. RESULTS Thirty-one participants (61% female) were included in a combined sample from the University of Washington (N = 9) and John Hopkins University (N = 22). Mean age was 14 ± 3 years, and BMI z-score was 0.7 ± 1.1 (26% with obesity). No study site-related differences were seen in T2 relaxation time across all nine regions (chi2 (8): 9.46, P = .30). Regional differences in T2 relaxation time were present (P < .001). MBH presented longer T2 relaxation time, suggestive of Gliosis, when compared to all regions (P < .001), including an intra-hypothalamic control. Physiological age-related declines in T2 relaxation times were found in grey matter ROIs, but not in the MBH (r = -0.14, P = .46). MBH was the only region with a positive correlation between T2 relaxation time and BMI z-score (r = 0.38, P = .03). CONCLUSIONS In a multi-site study, pilot data suggest that quantitative MRI detected normal maturation-related brain variation as well as evidence that MBH Gliosis is associated with increased adiposity in children.

  • Pilot multi-site and reproducibility study of hypothalamic Gliosis in children.
    Pediatric obesity, 2020
    Co-Authors: Leticia E Sewaybricker, Susan J Melhorn, Mary F. Webb, Afroditi Papantoni, Jun Hua, Christian L Roth, Susan Carnell, Ellen A Schur
    Abstract:

    Quantitative magnetic resonance imaging (MRI) evidence of mediobasal hypothalamic (MBH) Gliosis positively correlates with body mass index (BMI) in adults. This has neither been well explored in children nor have other brain regions involved in appetitive processing been tested for evidence of Gliosis. Multi-site cross-sectional study in children to test for differences in quantitative T2 signal (measure of Gliosis) by region and to assess relationships with age and BMI. Participants underwent brain MRI using the same equipment and protocol to quantify T2 relaxation time in six bilateral regions of interest (ROIs): putamen, caudate, ventral striatum, amygdala, hippocampus and MBH, and three control regions: white matter, motor cortex and dorsal hypothalamus. Thirty-one participants (61% female) were included in a combined sample from the University of Washington (N = 9) and John Hopkins University (N = 22). Mean age was 14 ± 3 years, and BMI z-score was 0.7 ± 1.1 (26% with obesity). No study site-related differences were seen in T2 relaxation time across all nine regions (chi2 (8): 9.46, P = .30). Regional differences in T2 relaxation time were present (P < .001). MBH presented longer T2 relaxation time, suggestive of Gliosis, when compared to all regions (P < .001), including an intra-hypothalamic control. Physiological age-related declines in T2 relaxation times were found in grey matter ROIs, but not in the MBH (r = -0.14, P = .46). MBH was the only region with a positive correlation between T2 relaxation time and BMI z-score (r = 0.38, P = .03). In a multi-site study, pilot data suggest that quantitative MRI detected normal maturation-related brain variation as well as evidence that MBH Gliosis is associated with increased adiposity in children. © 2020 World Obesity Federation.

  • 212-OR: Testosterone Deficiency Increases Hypothalamic Gliosis and Metabolic Risk
    Diabetes, 2020
    Co-Authors: Mauricio D. Dorfman, Ellen A Schur, Jeremy M. Frey, Kelly M. Ness, Anzela Niraula, Jenny E. Kanter, Karin E. Bornfeldt, Katya B. Rubinow, Joshua P Thaler
    Abstract:

    Obesity is associated with metabolic syndrome and Gliosis, the activation of microglia (brain macrophages) and astrocytes, in the mediobasal hypothalamus (MBH) of humans and rodents. Similarly, hypogonadism in males is associated with increased susceptibility to weight gain, metabolic syndrome and MBH Gliosis. Interventions that reduce glial activation in rodents result in protection from diet-induced obesity. Thus, we hypothesize that the combination of low testosterone and western diet causes Gliosis, which in turn increases obesity susceptibility. To test this hypothesis in a rodent model, we combined gonadectomy (GDX) or sham surgery with high-fat diet (HFD) feeding in adult male mice. GDX and HFD feeding synergistically induced a striking activation of MBH astrocytes along with increased numbers of MBH microglia. This Gliosis response was reversed to sham levels by testosterone replacement. After only 4 weeks of HFD feeding, differences in adiposity between GDX and sham groups were minimal with only a mild worsening of glucose tolerance. Thus, testosterone deficiency combined with HFD exposure elicits Gliosis prior to substantial weight gain, suggesting a direct impact on glial cell function. To characterize the transcriptional response to testosterone deprivation and HFD exposure, we have developed mouse strains with GFP-tagged ribosomes (L10A) in astrocytes and microglia to allow purification of glial cell-specific mRNA from whole hypothalamic tissue samples (tagged ribosome affinity purification (TRAP)). In preliminary analyses, we have confirmed >10-fold enrichment of cell-specific mRNAs with de-enrichment of neuronal transcripts. These studies help reveal novel mechanisms by which hypogonadism increases the predisposition to metabolic disease. Disclosure M.D. Dorfman: None. J. Frey: None. K.M. Ness: None. A. Niraula: None. J.E. Kanter: None. K. Bornfeldt: None. K. Rubinow: None. E. Schur: None. J. Thaler: None. Funding American Heart Association (16SDG27010018); Diabetes Research Center (P30DK017047); Novo Nordisk (A116079); National Institutes of Health (R01DK119754)

  • 1808-P: Is There Evidence of Gliosis Outside the Mediobasal Hypothalamus in Obese Adults?
    Diabetes, 2019
    Co-Authors: Jennifer L. Rosenbaum, Susan J Melhorn, Mary Rosalynn B. De Leon, Mary F. Webb, Ellen A Schur
    Abstract:

    Data increasingly support evidence of Gliosis in the mediobasal hypothalamus (MBH) in the setting of obesity and insulin resistance. It is if other regions of the brain are similarly affected. We tested if MBH Gliosis is related to radiologic evidence of Gliosis in selected subcortical, cortical, and hypothalamic regions. We recruited 40 obese adults (aged 25-61 y), with variable glucose tolerance by OGTT (n=24 normal glucose tolerance, n=11 impaired glucose tolerance and n=5 with T2DM). Individuals underwent a multi-echo T2 brain MRI. Two analysts placed regions of interest (ROIs) on the scans and determined the T2 relaxation time as a measure of Gliosis. ROIs included the MBH, amygdala, dorsomedial hypothalamus (DMH; area of the paraventricular nucleus), hippocampus, white matter (WM), cortex, caudate, ventral striatum (VS), and putamen. Left and right sides were averaged. High (n=13) and low (n=14) T2 groups were derived from the tertiles with the highest (strongest evidence for Gliosis) and lowest T2 relaxation times. The groups were compared by linear regression adjusted for age and sex. Mean BMI in the low T2 group was 35.7 ± 4.1 kg/m 2 and high T2 group was 37.1 ± 4.9 kg/m 2 . The groups did not differ in T2 relaxation time of WM (P=0.29), cortex (P=0.15), caudate (P=0.49), putamen (P=0.79), amygdala (P=0.09), or hippocampus (P=0.44). In the high T2 group, T2 relaxation time was shorter in the VS (adjusted mean 80.9±2.9 vs. 83.1±3.0, P=0.04) and longer in the DMH (adjusted mean 108.9±5.3 vs. 103.7±5.4, P=0.02), compared to the low T2 group. When subjects with T2DM (n=1 in low and n=3 in high T2 group) were excluded, the differences were attenuated (VSP=0.13; DMHP=0.10). The findings reveal preliminary evidence of longer T2 relaxation times in the DMH of obese individuals with signs of MBH Gliosis and no evidence for Gliosis in cortical or subcortical regions. Further study of Gliosis in the DMH and its relation to blood glucose control and autonomic function in humans, particularly in those with T2DM, is warranted. Disclosure J.L. Rosenbaum: None. S.J. Melhorn: None. M. De Leon: None. M. Webb: None. E. Schur: None. Funding American Diabetes Association (1-17-ICTS-085 to E.S.); National Institutes of Health (T32HL007028); University of Washington Institute of Translational Health Sciences (UL1TR002319)

  • initial evidence for hypothalamic Gliosis in children with obesity by quantitative t2 mri and implications for blood oxygen level dependent response to glucose ingestion
    Pediatric Obesity, 2018
    Co-Authors: Susan J Melhorn, Ellen A Schur, Leticia Esposito Sewaybricker, Brunno Machado De Campos, Mary K Askren, Guilherme Augusto Silva Nogueira, Mariana Porto Zambon, Maria A R G M Antonio, Fernando Cendes
    Abstract:

    OBJECTIVE In adults, hypothalamic Gliosis has been documented using quantitative T2 neuroimaging, whereas functional magnetic resonance imaging (fMRI) has shown a defective hypothalamic response to nutrients. No studies have yet evaluated these hypothalamic abnormalities in children with obesity. METHODS Children with obesity and lean controls underwent quantitative MRI measuring T2 relaxation time, along with continuous hypothalamic fMRI acquisition to evaluate early response to glucose ingestion. RESULTS Children with obesity (N = 11) had longer T2 relaxation times, consistent with Gliosis, in the mediobasal hypothalamus (MBH) compared to controls (N = 9; P = 0.004). Moreover, there was a highly significant group*region interaction (P = 0.002), demonstrating that signs of Gliosis were specific to MBH and not to reference regions. Longer T2 relaxation times correlated with measures of higher adiposity, including visceral fat percentage (P = 0.01). Mean glucose-induced hypothalamic blood oxygen-level dependent signal change did not differ between groups (P = 0.11). However, mean left MBH T2 relaxation time negatively correlated with glucose-induced hypothalamic signal change (P < 0.05). CONCLUSION Imaging signs of hypothalamic Gliosis were present in children with obesity and positively associated with more severe adiposity. Children with the strongest evidence for Gliosis showed the least activation after glucose ingestion. These initial findings suggest that the hypothalamus is both structurally and functionally affected in childhood obesity.

Susan J Melhorn - One of the best experts on this subject based on the ideXlab platform.

  • Pilot multi-site and reproducibility study of hypothalamic Gliosis in children.
    Pediatric obesity, 2020
    Co-Authors: Leticia E Sewaybricker, Susan J Melhorn, Mary F. Webb, Afroditi Papantoni, Jun Hua, Christian L Roth, Susan Carnell, Ellen A Schur
    Abstract:

    Quantitative magnetic resonance imaging (MRI) evidence of mediobasal hypothalamic (MBH) Gliosis positively correlates with body mass index (BMI) in adults. This has neither been well explored in children nor have other brain regions involved in appetitive processing been tested for evidence of Gliosis. Multi-site cross-sectional study in children to test for differences in quantitative T2 signal (measure of Gliosis) by region and to assess relationships with age and BMI. Participants underwent brain MRI using the same equipment and protocol to quantify T2 relaxation time in six bilateral regions of interest (ROIs): putamen, caudate, ventral striatum, amygdala, hippocampus and MBH, and three control regions: white matter, motor cortex and dorsal hypothalamus. Thirty-one participants (61% female) were included in a combined sample from the University of Washington (N = 9) and John Hopkins University (N = 22). Mean age was 14 ± 3 years, and BMI z-score was 0.7 ± 1.1 (26% with obesity). No study site-related differences were seen in T2 relaxation time across all nine regions (chi2 (8): 9.46, P = .30). Regional differences in T2 relaxation time were present (P < .001). MBH presented longer T2 relaxation time, suggestive of Gliosis, when compared to all regions (P < .001), including an intra-hypothalamic control. Physiological age-related declines in T2 relaxation times were found in grey matter ROIs, but not in the MBH (r = -0.14, P = .46). MBH was the only region with a positive correlation between T2 relaxation time and BMI z-score (r = 0.38, P = .03). In a multi-site study, pilot data suggest that quantitative MRI detected normal maturation-related brain variation as well as evidence that MBH Gliosis is associated with increased adiposity in children. © 2020 World Obesity Federation.

  • pilot multi site and reproducibility study of hypothalamic Gliosis in children
    Pediatric Obesity, 2020
    Co-Authors: Leticia Esposito Sewaybricker, Susan J Melhorn, Mary F. Webb, Afroditi Papantoni, Jun Hua, Christian L Roth, Susan Carnell, Ellen A Schur
    Abstract:

    OBJECTIVE Quantitative magnetic resonance imaging (MRI) evidence of mediobasal hypothalamic (MBH) Gliosis positively correlates with body mass index (BMI) in adults. This has neither been well explored in children nor have other brain regions involved in appetitive processing been tested for evidence of Gliosis. METHODS Multi-site cross-sectional study in children to test for differences in quantitative T2 signal (measure of Gliosis) by region and to assess relationships with age and BMI. Participants underwent brain MRI using the same equipment and protocol to quantify T2 relaxation time in six bilateral regions of interest (ROIs): putamen, caudate, ventral striatum, amygdala, hippocampus and MBH, and three control regions: white matter, motor cortex and dorsal hypothalamus. RESULTS Thirty-one participants (61% female) were included in a combined sample from the University of Washington (N = 9) and John Hopkins University (N = 22). Mean age was 14 ± 3 years, and BMI z-score was 0.7 ± 1.1 (26% with obesity). No study site-related differences were seen in T2 relaxation time across all nine regions (chi2 (8): 9.46, P = .30). Regional differences in T2 relaxation time were present (P < .001). MBH presented longer T2 relaxation time, suggestive of Gliosis, when compared to all regions (P < .001), including an intra-hypothalamic control. Physiological age-related declines in T2 relaxation times were found in grey matter ROIs, but not in the MBH (r = -0.14, P = .46). MBH was the only region with a positive correlation between T2 relaxation time and BMI z-score (r = 0.38, P = .03). CONCLUSIONS In a multi-site study, pilot data suggest that quantitative MRI detected normal maturation-related brain variation as well as evidence that MBH Gliosis is associated with increased adiposity in children.

  • 1808-P: Is There Evidence of Gliosis Outside the Mediobasal Hypothalamus in Obese Adults?
    Diabetes, 2019
    Co-Authors: Jennifer L. Rosenbaum, Susan J Melhorn, Mary Rosalynn B. De Leon, Mary F. Webb, Ellen A Schur
    Abstract:

    Data increasingly support evidence of Gliosis in the mediobasal hypothalamus (MBH) in the setting of obesity and insulin resistance. It is if other regions of the brain are similarly affected. We tested if MBH Gliosis is related to radiologic evidence of Gliosis in selected subcortical, cortical, and hypothalamic regions. We recruited 40 obese adults (aged 25-61 y), with variable glucose tolerance by OGTT (n=24 normal glucose tolerance, n=11 impaired glucose tolerance and n=5 with T2DM). Individuals underwent a multi-echo T2 brain MRI. Two analysts placed regions of interest (ROIs) on the scans and determined the T2 relaxation time as a measure of Gliosis. ROIs included the MBH, amygdala, dorsomedial hypothalamus (DMH; area of the paraventricular nucleus), hippocampus, white matter (WM), cortex, caudate, ventral striatum (VS), and putamen. Left and right sides were averaged. High (n=13) and low (n=14) T2 groups were derived from the tertiles with the highest (strongest evidence for Gliosis) and lowest T2 relaxation times. The groups were compared by linear regression adjusted for age and sex. Mean BMI in the low T2 group was 35.7 ± 4.1 kg/m 2 and high T2 group was 37.1 ± 4.9 kg/m 2 . The groups did not differ in T2 relaxation time of WM (P=0.29), cortex (P=0.15), caudate (P=0.49), putamen (P=0.79), amygdala (P=0.09), or hippocampus (P=0.44). In the high T2 group, T2 relaxation time was shorter in the VS (adjusted mean 80.9±2.9 vs. 83.1±3.0, P=0.04) and longer in the DMH (adjusted mean 108.9±5.3 vs. 103.7±5.4, P=0.02), compared to the low T2 group. When subjects with T2DM (n=1 in low and n=3 in high T2 group) were excluded, the differences were attenuated (VSP=0.13; DMHP=0.10). The findings reveal preliminary evidence of longer T2 relaxation times in the DMH of obese individuals with signs of MBH Gliosis and no evidence for Gliosis in cortical or subcortical regions. Further study of Gliosis in the DMH and its relation to blood glucose control and autonomic function in humans, particularly in those with T2DM, is warranted. Disclosure J.L. Rosenbaum: None. S.J. Melhorn: None. M. De Leon: None. M. Webb: None. E. Schur: None. Funding American Diabetes Association (1-17-ICTS-085 to E.S.); National Institutes of Health (T32HL007028); University of Washington Institute of Translational Health Sciences (UL1TR002319)

  • initial evidence for hypothalamic Gliosis in children with obesity by quantitative t2 mri and implications for blood oxygen level dependent response to glucose ingestion
    Pediatric Obesity, 2018
    Co-Authors: Susan J Melhorn, Ellen A Schur, Leticia Esposito Sewaybricker, Brunno Machado De Campos, Mary K Askren, Guilherme Augusto Silva Nogueira, Mariana Porto Zambon, Maria A R G M Antonio, Fernando Cendes
    Abstract:

    OBJECTIVE In adults, hypothalamic Gliosis has been documented using quantitative T2 neuroimaging, whereas functional magnetic resonance imaging (fMRI) has shown a defective hypothalamic response to nutrients. No studies have yet evaluated these hypothalamic abnormalities in children with obesity. METHODS Children with obesity and lean controls underwent quantitative MRI measuring T2 relaxation time, along with continuous hypothalamic fMRI acquisition to evaluate early response to glucose ingestion. RESULTS Children with obesity (N = 11) had longer T2 relaxation times, consistent with Gliosis, in the mediobasal hypothalamus (MBH) compared to controls (N = 9; P = 0.004). Moreover, there was a highly significant group*region interaction (P = 0.002), demonstrating that signs of Gliosis were specific to MBH and not to reference regions. Longer T2 relaxation times correlated with measures of higher adiposity, including visceral fat percentage (P = 0.01). Mean glucose-induced hypothalamic blood oxygen-level dependent signal change did not differ between groups (P = 0.11). However, mean left MBH T2 relaxation time negatively correlated with glucose-induced hypothalamic signal change (P < 0.05). CONCLUSION Imaging signs of hypothalamic Gliosis were present in children with obesity and positively associated with more severe adiposity. Children with the strongest evidence for Gliosis showed the least activation after glucose ingestion. These initial findings suggest that the hypothalamus is both structurally and functionally affected in childhood obesity.

  • hypothalamic Gliosis by mri and visceral fat mass negatively correlate with plasma testosterone concentrations in healthy men
    Obesity, 2018
    Co-Authors: Kathryn E Berkseth, Susan J Melhorn, Mary Rosalynn B. De Leon, Mary F. Webb, Katya B. Rubinow, Brett T Marck, Alvin M Matsumoto, John K Amory, Stephanie T Page, Ellen A Schur
    Abstract:

    OBJECTIVE This study aimed to determine whether a relationship was evident between Gliosis in the mediobasal hypothalamus (MBH) and plasma testosterone concentrations in men. METHODS A total of 41 adult men (aged 18-50 years) from 23 twin pairs underwent fasting morning blood draw and brain magnetic resonance imaging. T2 relaxation time was used to quantify Gliosis in the MBH and control areas in the putamen and amygdala. Plasma concentrations of testosterone and 17β-estradiol were measured by liquid chromatography-tandem mass spectrometry. Body composition including visceral adiposity was measured by dual x-ray absorptiometry. RESULTS A negative association was found between MBH T2 relaxation time and plasma concentrations of both free and total testosterone (r = -0.29, P < 0.05 and r = -0.37, P < 0.01, respectively). Visceral adiposity exhibited a negative correlation with plasma total testosterone concentration (r = -0.45, P = 0.001) but a positive correlation with MBH T2 relaxation time (r = 0.24, P = 0.03). The negative correlation between plasma total testosterone and MBH T2 relaxation time remained significant after adjustment for visceral adiposity, age, BMI, and insulin resistance. CONCLUSIONS In healthy men across a range of BMIs, MBH Gliosis was associated with higher visceral adiposity but lower endogenous testosterone. These findings suggest that MBH Gliosis could provide novel mechanistic insights into gonadal dysfunction in men with obesity.

Leticia Esposito Sewaybricker - One of the best experts on this subject based on the ideXlab platform.

  • pilot multi site and reproducibility study of hypothalamic Gliosis in children
    Pediatric Obesity, 2020
    Co-Authors: Leticia Esposito Sewaybricker, Susan J Melhorn, Mary F. Webb, Afroditi Papantoni, Jun Hua, Christian L Roth, Susan Carnell, Ellen A Schur
    Abstract:

    OBJECTIVE Quantitative magnetic resonance imaging (MRI) evidence of mediobasal hypothalamic (MBH) Gliosis positively correlates with body mass index (BMI) in adults. This has neither been well explored in children nor have other brain regions involved in appetitive processing been tested for evidence of Gliosis. METHODS Multi-site cross-sectional study in children to test for differences in quantitative T2 signal (measure of Gliosis) by region and to assess relationships with age and BMI. Participants underwent brain MRI using the same equipment and protocol to quantify T2 relaxation time in six bilateral regions of interest (ROIs): putamen, caudate, ventral striatum, amygdala, hippocampus and MBH, and three control regions: white matter, motor cortex and dorsal hypothalamus. RESULTS Thirty-one participants (61% female) were included in a combined sample from the University of Washington (N = 9) and John Hopkins University (N = 22). Mean age was 14 ± 3 years, and BMI z-score was 0.7 ± 1.1 (26% with obesity). No study site-related differences were seen in T2 relaxation time across all nine regions (chi2 (8): 9.46, P = .30). Regional differences in T2 relaxation time were present (P < .001). MBH presented longer T2 relaxation time, suggestive of Gliosis, when compared to all regions (P < .001), including an intra-hypothalamic control. Physiological age-related declines in T2 relaxation times were found in grey matter ROIs, but not in the MBH (r = -0.14, P = .46). MBH was the only region with a positive correlation between T2 relaxation time and BMI z-score (r = 0.38, P = .03). CONCLUSIONS In a multi-site study, pilot data suggest that quantitative MRI detected normal maturation-related brain variation as well as evidence that MBH Gliosis is associated with increased adiposity in children.

  • initial evidence for hypothalamic Gliosis in children with obesity by quantitative t2 mri and implications for blood oxygen level dependent response to glucose ingestion
    Pediatric Obesity, 2018
    Co-Authors: Susan J Melhorn, Ellen A Schur, Leticia Esposito Sewaybricker, Brunno Machado De Campos, Mary K Askren, Guilherme Augusto Silva Nogueira, Mariana Porto Zambon, Maria A R G M Antonio, Fernando Cendes
    Abstract:

    OBJECTIVE In adults, hypothalamic Gliosis has been documented using quantitative T2 neuroimaging, whereas functional magnetic resonance imaging (fMRI) has shown a defective hypothalamic response to nutrients. No studies have yet evaluated these hypothalamic abnormalities in children with obesity. METHODS Children with obesity and lean controls underwent quantitative MRI measuring T2 relaxation time, along with continuous hypothalamic fMRI acquisition to evaluate early response to glucose ingestion. RESULTS Children with obesity (N = 11) had longer T2 relaxation times, consistent with Gliosis, in the mediobasal hypothalamus (MBH) compared to controls (N = 9; P = 0.004). Moreover, there was a highly significant group*region interaction (P = 0.002), demonstrating that signs of Gliosis were specific to MBH and not to reference regions. Longer T2 relaxation times correlated with measures of higher adiposity, including visceral fat percentage (P = 0.01). Mean glucose-induced hypothalamic blood oxygen-level dependent signal change did not differ between groups (P = 0.11). However, mean left MBH T2 relaxation time negatively correlated with glucose-induced hypothalamic signal change (P < 0.05). CONCLUSION Imaging signs of hypothalamic Gliosis were present in children with obesity and positively associated with more severe adiposity. Children with the strongest evidence for Gliosis showed the least activation after glucose ingestion. These initial findings suggest that the hypothalamus is both structurally and functionally affected in childhood obesity.

Fernando Cendes - One of the best experts on this subject based on the ideXlab platform.

  • initial evidence for hypothalamic Gliosis in children with obesity by quantitative t2 mri and implications for blood oxygen level dependent response to glucose ingestion
    Pediatric Obesity, 2018
    Co-Authors: Susan J Melhorn, Ellen A Schur, Leticia Esposito Sewaybricker, Brunno Machado De Campos, Mary K Askren, Guilherme Augusto Silva Nogueira, Mariana Porto Zambon, Maria A R G M Antonio, Fernando Cendes
    Abstract:

    OBJECTIVE In adults, hypothalamic Gliosis has been documented using quantitative T2 neuroimaging, whereas functional magnetic resonance imaging (fMRI) has shown a defective hypothalamic response to nutrients. No studies have yet evaluated these hypothalamic abnormalities in children with obesity. METHODS Children with obesity and lean controls underwent quantitative MRI measuring T2 relaxation time, along with continuous hypothalamic fMRI acquisition to evaluate early response to glucose ingestion. RESULTS Children with obesity (N = 11) had longer T2 relaxation times, consistent with Gliosis, in the mediobasal hypothalamus (MBH) compared to controls (N = 9; P = 0.004). Moreover, there was a highly significant group*region interaction (P = 0.002), demonstrating that signs of Gliosis were specific to MBH and not to reference regions. Longer T2 relaxation times correlated with measures of higher adiposity, including visceral fat percentage (P = 0.01). Mean glucose-induced hypothalamic blood oxygen-level dependent signal change did not differ between groups (P = 0.11). However, mean left MBH T2 relaxation time negatively correlated with glucose-induced hypothalamic signal change (P < 0.05). CONCLUSION Imaging signs of hypothalamic Gliosis were present in children with obesity and positively associated with more severe adiposity. Children with the strongest evidence for Gliosis showed the least activation after glucose ingestion. These initial findings suggest that the hypothalamus is both structurally and functionally affected in childhood obesity.

  • international consensus classification of hippocampal sclerosis in temporal lobe epilepsy a task force report from the ilae commission on diagnostic methods
    Epilepsia, 2013
    Co-Authors: Ingmar Blumcke, Fernando Cendes, M Thom, Eleonora Aronica, Dawna D Armstrong, Fabrice Bartolomei, Andrea Bernasconi, Neda Bernasconi, Christian G Bien, Roland Coras
    Abstract:

    Hippocampal sclerosis (HS) is the most frequent histopathology encountered in patients with drug-resistant temporal lobe epilepsy (TLE). Over the past decades, various attempts have been made to classify specific patterns of hippocampal neuronal cell loss and correlate subtypes with postsurgical outcome. However, no international consensus about definitions and terminology has been achieved. A task force reviewed previous classification schemes and proposes a system based on semiquantitative hippocampal cell loss patterns that can be applied in any histopathology laboratory. Interobserver and intraobserver agreement studies reached consensus to classify three types in anatomically well-preserved hippocampal specimens: HS International League Against Epilepsy (ILAE) type 1 refers always to severe neuronal cell loss and Gliosis predominantly in CA1 and CA4 regions, compared to CA1 predominant neuronal cell loss and Gliosis (HS ILAE type 2), or CA4 predominant neuronal cell loss and Gliosis (HS ILAE type 3). Surgical hippocampus specimens obtained from patients with TLE may also show normal content of neurons with reactive Gliosis only (no-HS). HS ILAE type 1 is more often associated with a history of initial precipitating injuries before age 5 years, with early seizure onset, and favorable postsurgical seizure control. CA1 predominant HS ILAE type 2 and CA4 predominant HS ILAE type 3 have been studied less systematically so far, but some reports point to less favorable outcome, and to differences regarding epilepsy history, including age of seizure onset. The proposed international consensus classification will aid in the characterization of specific clinicopathologic syndromes, and explore variability in imaging and electrophysiology findings, and in postsurgical seizure control

Mary F. Webb - One of the best experts on this subject based on the ideXlab platform.

  • Pilot multi-site and reproducibility study of hypothalamic Gliosis in children.
    Pediatric obesity, 2020
    Co-Authors: Leticia E Sewaybricker, Susan J Melhorn, Mary F. Webb, Afroditi Papantoni, Jun Hua, Christian L Roth, Susan Carnell, Ellen A Schur
    Abstract:

    Quantitative magnetic resonance imaging (MRI) evidence of mediobasal hypothalamic (MBH) Gliosis positively correlates with body mass index (BMI) in adults. This has neither been well explored in children nor have other brain regions involved in appetitive processing been tested for evidence of Gliosis. Multi-site cross-sectional study in children to test for differences in quantitative T2 signal (measure of Gliosis) by region and to assess relationships with age and BMI. Participants underwent brain MRI using the same equipment and protocol to quantify T2 relaxation time in six bilateral regions of interest (ROIs): putamen, caudate, ventral striatum, amygdala, hippocampus and MBH, and three control regions: white matter, motor cortex and dorsal hypothalamus. Thirty-one participants (61% female) were included in a combined sample from the University of Washington (N = 9) and John Hopkins University (N = 22). Mean age was 14 ± 3 years, and BMI z-score was 0.7 ± 1.1 (26% with obesity). No study site-related differences were seen in T2 relaxation time across all nine regions (chi2 (8): 9.46, P = .30). Regional differences in T2 relaxation time were present (P < .001). MBH presented longer T2 relaxation time, suggestive of Gliosis, when compared to all regions (P < .001), including an intra-hypothalamic control. Physiological age-related declines in T2 relaxation times were found in grey matter ROIs, but not in the MBH (r = -0.14, P = .46). MBH was the only region with a positive correlation between T2 relaxation time and BMI z-score (r = 0.38, P = .03). In a multi-site study, pilot data suggest that quantitative MRI detected normal maturation-related brain variation as well as evidence that MBH Gliosis is associated with increased adiposity in children. © 2020 World Obesity Federation.

  • pilot multi site and reproducibility study of hypothalamic Gliosis in children
    Pediatric Obesity, 2020
    Co-Authors: Leticia Esposito Sewaybricker, Susan J Melhorn, Mary F. Webb, Afroditi Papantoni, Jun Hua, Christian L Roth, Susan Carnell, Ellen A Schur
    Abstract:

    OBJECTIVE Quantitative magnetic resonance imaging (MRI) evidence of mediobasal hypothalamic (MBH) Gliosis positively correlates with body mass index (BMI) in adults. This has neither been well explored in children nor have other brain regions involved in appetitive processing been tested for evidence of Gliosis. METHODS Multi-site cross-sectional study in children to test for differences in quantitative T2 signal (measure of Gliosis) by region and to assess relationships with age and BMI. Participants underwent brain MRI using the same equipment and protocol to quantify T2 relaxation time in six bilateral regions of interest (ROIs): putamen, caudate, ventral striatum, amygdala, hippocampus and MBH, and three control regions: white matter, motor cortex and dorsal hypothalamus. RESULTS Thirty-one participants (61% female) were included in a combined sample from the University of Washington (N = 9) and John Hopkins University (N = 22). Mean age was 14 ± 3 years, and BMI z-score was 0.7 ± 1.1 (26% with obesity). No study site-related differences were seen in T2 relaxation time across all nine regions (chi2 (8): 9.46, P = .30). Regional differences in T2 relaxation time were present (P < .001). MBH presented longer T2 relaxation time, suggestive of Gliosis, when compared to all regions (P < .001), including an intra-hypothalamic control. Physiological age-related declines in T2 relaxation times were found in grey matter ROIs, but not in the MBH (r = -0.14, P = .46). MBH was the only region with a positive correlation between T2 relaxation time and BMI z-score (r = 0.38, P = .03). CONCLUSIONS In a multi-site study, pilot data suggest that quantitative MRI detected normal maturation-related brain variation as well as evidence that MBH Gliosis is associated with increased adiposity in children.

  • 1808-P: Is There Evidence of Gliosis Outside the Mediobasal Hypothalamus in Obese Adults?
    Diabetes, 2019
    Co-Authors: Jennifer L. Rosenbaum, Susan J Melhorn, Mary Rosalynn B. De Leon, Mary F. Webb, Ellen A Schur
    Abstract:

    Data increasingly support evidence of Gliosis in the mediobasal hypothalamus (MBH) in the setting of obesity and insulin resistance. It is if other regions of the brain are similarly affected. We tested if MBH Gliosis is related to radiologic evidence of Gliosis in selected subcortical, cortical, and hypothalamic regions. We recruited 40 obese adults (aged 25-61 y), with variable glucose tolerance by OGTT (n=24 normal glucose tolerance, n=11 impaired glucose tolerance and n=5 with T2DM). Individuals underwent a multi-echo T2 brain MRI. Two analysts placed regions of interest (ROIs) on the scans and determined the T2 relaxation time as a measure of Gliosis. ROIs included the MBH, amygdala, dorsomedial hypothalamus (DMH; area of the paraventricular nucleus), hippocampus, white matter (WM), cortex, caudate, ventral striatum (VS), and putamen. Left and right sides were averaged. High (n=13) and low (n=14) T2 groups were derived from the tertiles with the highest (strongest evidence for Gliosis) and lowest T2 relaxation times. The groups were compared by linear regression adjusted for age and sex. Mean BMI in the low T2 group was 35.7 ± 4.1 kg/m 2 and high T2 group was 37.1 ± 4.9 kg/m 2 . The groups did not differ in T2 relaxation time of WM (P=0.29), cortex (P=0.15), caudate (P=0.49), putamen (P=0.79), amygdala (P=0.09), or hippocampus (P=0.44). In the high T2 group, T2 relaxation time was shorter in the VS (adjusted mean 80.9±2.9 vs. 83.1±3.0, P=0.04) and longer in the DMH (adjusted mean 108.9±5.3 vs. 103.7±5.4, P=0.02), compared to the low T2 group. When subjects with T2DM (n=1 in low and n=3 in high T2 group) were excluded, the differences were attenuated (VSP=0.13; DMHP=0.10). The findings reveal preliminary evidence of longer T2 relaxation times in the DMH of obese individuals with signs of MBH Gliosis and no evidence for Gliosis in cortical or subcortical regions. Further study of Gliosis in the DMH and its relation to blood glucose control and autonomic function in humans, particularly in those with T2DM, is warranted. Disclosure J.L. Rosenbaum: None. S.J. Melhorn: None. M. De Leon: None. M. Webb: None. E. Schur: None. Funding American Diabetes Association (1-17-ICTS-085 to E.S.); National Institutes of Health (T32HL007028); University of Washington Institute of Translational Health Sciences (UL1TR002319)

  • hypothalamic Gliosis by mri and visceral fat mass negatively correlate with plasma testosterone concentrations in healthy men
    Obesity, 2018
    Co-Authors: Kathryn E Berkseth, Susan J Melhorn, Mary Rosalynn B. De Leon, Mary F. Webb, Katya B. Rubinow, Brett T Marck, Alvin M Matsumoto, John K Amory, Stephanie T Page, Ellen A Schur
    Abstract:

    OBJECTIVE This study aimed to determine whether a relationship was evident between Gliosis in the mediobasal hypothalamus (MBH) and plasma testosterone concentrations in men. METHODS A total of 41 adult men (aged 18-50 years) from 23 twin pairs underwent fasting morning blood draw and brain magnetic resonance imaging. T2 relaxation time was used to quantify Gliosis in the MBH and control areas in the putamen and amygdala. Plasma concentrations of testosterone and 17β-estradiol were measured by liquid chromatography-tandem mass spectrometry. Body composition including visceral adiposity was measured by dual x-ray absorptiometry. RESULTS A negative association was found between MBH T2 relaxation time and plasma concentrations of both free and total testosterone (r = -0.29, P < 0.05 and r = -0.37, P < 0.01, respectively). Visceral adiposity exhibited a negative correlation with plasma total testosterone concentration (r = -0.45, P = 0.001) but a positive correlation with MBH T2 relaxation time (r = 0.24, P = 0.03). The negative correlation between plasma total testosterone and MBH T2 relaxation time remained significant after adjustment for visceral adiposity, age, BMI, and insulin resistance. CONCLUSIONS In healthy men across a range of BMIs, MBH Gliosis was associated with higher visceral adiposity but lower endogenous testosterone. These findings suggest that MBH Gliosis could provide novel mechanistic insights into gonadal dysfunction in men with obesity.

  • radiologic evidence that hypothalamic Gliosis is associated with obesity and insulin resistance in humans
    Obesity, 2015
    Co-Authors: Ellen A Schur, Kathryn E Berkseth, Stephan J Guyenet, Susan J Melhorn, Vidhi Tyagi, Joshua A. Sonnen, Matthew J Lacy, Mary Rosalynn, B De Leon, Mary F. Webb
    Abstract:

    Objective To use quantitative magnetic resonance imaging (MRI) to test whether mediobasal hypothalamic (MBH) Gliosis is associated with obesity and insulin resistance in humans. Methods Sixty-seven participants underwent a fasting blood draw and MRI. Cases with radiologic evidence of MBH Gliosis (N = 22) were identified as the upper tertile of left MBH T2 relaxation time and were compared to controls (N = 23) from the lowest tertile. In a separate postmortem study, brain slices (N = 10) through the MBH were imaged by MRI and stained for glial fibrillary acidic protein (GFAP). Results In all participants, longer T2 relaxation time in the left MBH was associated with higher BMI (P = 0.01). Compared with controls, cases had longer T2 relaxation times in the right MBH (P < 0.05), as well as higher BMI (P < 0.05), fasting insulin concentrations (P < 0.01), and HOMA-IR values (P < 0.01), adjusted for sex and age. Elevations in insulin and HOMA-IR were also independent of BMI. In the postmortem study, GFAP staining intensity was positively associated with MBH T2 relaxation time (P < 0.05), validating an MRI-based method for the detection of MBH Gliosis in humans. Conclusions These findings link hypothalamic Gliosis to insulin resistance in humans and suggest that the link is independent of the level of adiposity.