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Oklahoma City, OK, United States

Tran L.,Oklahoma Center for Neuroscience | Greenwood-Van Meerveld B.,Oklahoma Center for Neuroscience | Greenwood-Van Meerveld B.,The University of Oklahoma Health Sciences Center
Journals of Gerontology - Series A Biological Sciences and Medical Sciences | Year: 2013

Disorders of the gastrointestinal tract are common in the elderly people; however, the precise trait(s) of aging that contribute to the vulnerability of the gastrointestinal tract are poorly understood. Recent evidence suggests that patients with gastrointestinal disorders have increased intestinal permeability. Here, we address the hypothesis that disruption of the intestinal barrier is associated with aging. Our results demonstrated that permeability was significantly higher in colonic biopsies collected from old baboons compared with young baboons. Additionally, colonic tissue from the older animals had decreased zonula occluden-1, occludin, and junctional adhesion molecule-A tight junction protein expression and increased claudin-2 expression. Upregulation of miR-29a and inflammatory cytokines IFN-γ, IL-6, and IL-1β was also found in colonic biopsies from old baboons relative to young baboons. These results show for the first time that a pivotal contributing factor to geriatric vulnerability to gastrointestinal dysfunction may be increased colonic permeability via age-associated remodeling of intestinal epithelial tight junction proteins. © 2013 The Author.


Doblas S.,Oklahoma Medical Research Foundation | Doblas S.,French Institute of Health and Medical Research | He T.,Oklahoma Medical Research Foundation | He T.,Oklahoma Center for Neuroscience | And 8 more authors.
NMR in Biomedicine | Year: 2012

The assessment of metabolites by 1H MRS can provide information regarding glioma growth, and may be able to distinguish between different glioma models. Rat C6, 9L/LacZ, F98 and RG2, and mouse GL261, cells were intracerebrally implanted into the respective rodents, and human U87 MG cells were implanted into athymic rats. Ethyl-nitrosourea induction was also used. Glioma metabolites [e.g. total choline (tCho), total creatine (tCr), N-acetylaspartate (NAA), lactate (Lac), glutamine (Gln), glutamate (Glu), aspartate (Asp), guanosine (Gua), mobile lipids and macromolecules (MMs)] were assessed from 1H MRS using point-resolved spectroscopy (PRESS) [TE=24ms; TR=2500ms; variable pulse power and optimized relaxation delay (VAPOR) water suppression; 27-μL and 8-μL voxels in rats and mice, respectively] at 7T. Alterations in metabolites (Totally Automatic Robust Quantitation in NMR, TARQUIN) in tumors were characterized by increases in lipids (Lip1.3: 8.8-54.5m m for C6 and GL261) and decreases in NAA (1.3-2.0m m for RG2, GL261 and C6) and tCr (0.8-4.0m m for F98, RG2, GL261 and C6) in some models. F98, RG2, GL261 and C6 models all showed significantly decreased (p<0.05) tCr, and RG2, GL261 and C6 models all exhibited significantly decreased (p<0.05) NAA. The RG2 model showed significantly decreased (p<0.05) Gln and Glu, the C6 model significantly decreased (p<0.05) Asp, and the F98 and U87 models significantly decreased (p<0.05) Gua, compared with controls. The GL261 model showed the greatest alterations in metabolites. 1H MRS was able to differentiate the metabolic profiles in many of the seven rodent glioma models assessed. These models are considered to resemble certain characteristics of human glioblastomas, and this study may be helpful in selecting appropriate models. © 2011 John Wiley & Sons, Ltd.


Chaloner A.,Medical Center 151G | Chaloner A.,Oklahoma Center for Neuroscience | Greenwood-Van Meerveld B.,Medical Center 151G | Greenwood-Van Meerveld B.,Oklahoma Center for Neuroscience | Greenwood-Van Meerveld B.,The University of Oklahoma Health Sciences Center
Journal of Pain | Year: 2013

Visceral pain is the hallmark feature of irritable bowel syndrome (IBS), a gastrointestinal disorder, which is more commonly diagnosed in women. Female IBS patients frequently report a history of early life adversity (ELA); however, sex differences in ELA-induced visceral pain and the role of ovarian hormones have yet to be investigated. Therefore, we tested the hypothesis that ELA induces visceral hypersensitivity through a sexually dimorphic mechanism mediated via estradiol. As a model of ELA, neonatal rats were exposed to different pairings of an odor and shock to control for trauma predictability. In adulthood, visceral sensitivity was assessed via a visceromotor response to colorectal distension. Following ovariectomy and estradiol replacement in a separate group of rats, the visceral sensitivity was quantified. We found that females that received unpredictable odor-shock developed visceral hypersensitivity in adulthood. In contrast, visceral sensitivity was not significantly different following ELA in adult males. Ovariectomy reversed visceral hypersensitivity following unpredictable ELA, whereas estradiol replacement reestablished visceral hypersensitivity in the unpredictable group. This study is the first to show sex-related differences in visceral sensitivity following unpredictable ELA. Our data highlight the activational effect of estradiol as a pivotal mechanism in maintaining visceral hypersensitivity. Perspective: This article directly implicates a critical role for ovarian hormones in maintaining visceral hypersensitivity following ELA, specifically identifying the activational effect of estradiol as a key modulator of visceral sensitivity. These data suggest that ELA induces persistent functional abdominal pain in female IBS patients through an estrogen-dependent mechanism. © 2013 by the American Pain Society.


Doblas S.,Oklahoma Medical Research Foundation | He T.,Oklahoma Medical Research Foundation | He T.,Oklahoma Center for Neuroscience | Saunders D.,Oklahoma Medical Research Foundation | And 6 more authors.
Journal of Magnetic Resonance Imaging | Year: 2010

Purpose: To evaluate the added value of non-contrast-enhanced MR angiography (MRA) to conventional MR imaging for a detailed characterization of different rodent glioma models. Materials and Methods: Intracerebral tumor cell implantation and chemical induction methods were implemented to obtain rat C6, 9L/LacZ, F98, RG2, and ethyl-nitrosourea (ENU) -induced glioma models, a human U87 MG tumor model as well as a mouse GL261 glioma model. MR assessments were regularly conducted on a 7 Tesla Bruker BioSpin system. The tumor border sharpness and growth characteristics of each glioma model were assessed from T 2-weighted images. Neovascularization and vascular alterations inherent to each model were characterized by assessing absolute blood volumes, vessel density, length, and diameter using Mathematica and Amira software. Results: The 9L/LacZ and ENU gliomas both presented flaws that hinder their use as reliable brain tumor models. C6 gliomas were slightly invasive and induced moderate vascular alterations, whereas GL261 tumors dramatically altered the brain vessels in the glioma region. F98, RG2, and U87 are infiltrative models that produced dramatic vascular alterations. Conclusion: MRI and MRA provided crucial in vivo information to identify a distinctive "fingerprint" for each of our seven rodent glioma models. © 2010 Wiley-Liss, Inc.


Moloney R.D.,University College Cork | Moloney R.D.,The University of Oklahoma Health Sciences Center | Johnson A.C.,The University of Oklahoma Health Sciences Center | O'Mahony S.M.,University College Cork | And 5 more authors.
CNS Neuroscience and Therapeutics | Year: 2016

Visceral pain is a global term used to describe pain originating from the internal organs of the body, which affects a significant proportion of the population and is a common feature of functional gastrointestinal disorders (FGIDs) such as irritable bowel syndrome (IBS). While IBS is multifactorial, with no single etiology to completely explain the disorder, many patients also experience comorbid behavioral disorders, such as anxiety or depression; thus, IBS is described as a disorder of the gut-brain axis. Stress is implicated in the development and exacerbation of visceral pain disorders. Chronic stress can modify central pain circuitry, as well as change motility and permeability throughout the gastrointestinal (GI) tract. More recently, the role of the gut microbiota in the bidirectional communication along the gut-brain axis, and subsequent changes in behavior, has emerged. Thus, stress and the gut microbiota can interact through complementary or opposing factors to influence visceral nociceptive behaviors. This review will highlight the evidence by which stress and the gut microbiota interact in the regulation of visceral nociception. We will focus on the influence of stress on the microbiota and the mechanisms by which microbiota can affect the stress response and behavioral outcomes with an emphasis on visceral pain. © 2016 John Wiley & Sons Ltd.

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