Medicine and Health Sciences Commons^™

Pretreatment Of Human Cerebrovascular Endothelial Cells With Co-Releasing Molecule-3 Interferes With Jnk/Ap-1 Signaling And Suppresses Lps-Induced Proadhesive Phenotype., Fukashi Serizawa, Eric Patterson, Richard F Potter, Douglas D Fraser, Gediminas Cepinskas

Medical Biophysics Publications

OBJECTIVE: Exogenously administered CO interferes with PMN recruitment to the inflamed organs. The mechanisms of CO-dependent modulation of vascular proadhesive phenotype, a key step in PMN recruitment, are unclear.

METHODS: We assessed the effects/mechanisms of CO liberated from a water-soluble CORM-3 on modulation of the proadhesive phenotype in hCMEC/D3 in an in vitro model of endotoxemia. To this end, hCMEC/D3 were stimulated with LPS (1 μg/mL) for six hours. In some experiments hCMEC/D3 were pretreated with CORM-3 (200 μmol/L) before LPS-stimulation. PMN rolling/adhesion to hCMEC/D3 were assessed under conditions of laminar shear stress (0.7 dyn/cm(2) ). In parallel, expression of …

Hippocampal Volume, Early Cognitive Decline And Gait Variability: Which Association?, Olivier Beauchet, Cyrille P Launay, Cédric Annweiler, Gilles Allali

Medical Biophysics Publications

BACKGROUND: In contrast to its prominent function in cognition, the involvement of the hippocampus in gait control is still a matter of debate. The present study aimed to examine the association of the hippocampal volume with mean values and coefficients of variation (CoV) of spatio-temporal gait parameters among cognitively healthy individuals (CHI) and patients with mild cognitive impairment (MCI).

METHODS: A total of 90 individuals (47 CHI with a mean age of 69.7±3.6years and 48.9% women, and 43 MCI individuals with a mean age of 70.2±3.7years and 62.8% women) were included in this cross-sectional study. The hippocampal volume was quantified …

'Vitamin D And Cognition In Older Adults': Updated International Recommendations., C Annweiler, E Dursun, F Féron, D Gezen-Ak, A V Kalueff, T Littlejohns, D J Llewellyn, P Millet, T Scott, K L Tucker, S Yilmazer, O Beauchet

Medical Biophysics Publications

BACKGROUND: Hypovitaminosis D, a condition that is highly prevalent in older adults aged 65 years and above, is associated with brain changes and dementia. Given the rapidly accumulating and complex contribution of the literature in the field of vitamin D and cognition, clear guidance is needed for researchers and clinicians.

METHODS: International experts met at an invitational summit on 'Vitamin D and Cognition in Older Adults'. Based on previous reports and expert opinion, the task force focused on key questions relating to the role of vitamin D in Alzheimer's disease and related disorders. Each question was discussed and voted using …

Validation Of Volumetric And Single-Slice Mri Adipose Analysis Using A Novel Fully Automated Segmentation Method., Bryan T Addeman, Shelby Kutty, Thomas G Perkins, Abraam S Soliman, Curtis N Wiens, Colin M Mccurdy, Melanie D Beaton, Robert A Hegele, Charles Mckenzie

Medical Biophysics Publications

PURPOSE: To validate a fully automated adipose segmentation method with magnetic resonance imaging (MRI) fat fraction abdominal imaging. We hypothesized that this method is suitable for segmentation of subcutaneous adipose tissue (SAT) and intra-abdominal adipose tissue (IAAT) in a wide population range, easy to use, works with a variety of hardware setups, and is highly repeatable.

MATERIALS AND METHODS: Analysis was performed comparing precision and analysis time of manual and automated segmentation of single-slice imaging, and volumetric imaging (78-88 slices). Volumetric and single-slice data were acquired in a variety of cohorts (body mass index [BMI] 15.6-41.76) including healthy adult volunteers, …

Unified Voxel- And Tensor-Based Morphometry (Uvtbm) Using Registration Confidence., Ali R Khan, Lei Wang, Mirza Faisal Beg

Medical Biophysics Publications

Voxel-based morphometry (VBM) and tensor-based morphometry (TBM) both rely on spatial normalization to a template and yet have different requirements for the level of registration accuracy. VBM requires only global alignment of brain structures, with limited degrees of freedom in transformation, whereas TBM performs best when the registration is highly deformable and can achieve higher registration accuracy. In addition, the registration accuracy varies over the whole brain, with higher accuracy typically observed in subcortical areas and lower accuracy seen in cortical areas. Hence, even the determinant of Jacobian of registration maps is spatially varying in their accuracy, and combining these …

The Effects Of Nonvascularized Versus Vascularized Bone Grafting On Calvarial Defect Healing., Stephanie M Power, Damir B Matic, David W Holdsworth

Medical Biophysics Publications

It remains unknown whether bone graft vascularity influences calvarial healing. The purposes of this study were (1) to develop a model to study nonvascularized and vascularized calvarial grafts as well as (2) to compare effects of bone graft vascularity on calvarial healing. Bilateral calvarial defects were created in 26 Wistar rats. The defects were left empty within 1 parietal region. On the contralateral side, the defects were partially closed with native parietal bone (control group, n = 6), nonvascularized (N-V, n = 10), or vascularized bone grafts (VAS, n = 10). The vascularized grafts were supplied by perforating dural arterioles. …

Tracking The Fate Of Stem Cell Implants With Fluorine-19 Mri., Jeffrey M Gaudet, Emeline J Ribot, Yuhua Chen, Kyle M Gilbert, Paula J Foster

Medical Biophysics Publications

BACKGROUND: In this study we used cellular magnetic resonance imaging (MRI) to detect mesenchymal stem cells (MSC) labeled with a Fluorine-19 (19F) agent. 19F-MRI offers unambiguous detection and in vivo quantification of labeled cells.

METHODS: We investigated two common stem cell transplant mouse models: an immune competent, syngeneic transplant model and an immune compromised, xenograft transplant model. 19F labelled stem cells were implanted intramuscularly into the hindlimb of healthy mice. The transplant was then monitored for up to 17 days using 19F-MRI, after which the tissue was excised for fluorescence microscopy and immunohistochemisty.

RESULTS: Immediately following transplantation, 19F-MRI quantification correlated …

Human Severe Sepsis Cytokine Mixture Increases Β2-Integrin-Dependent Polymorphonuclear Leukocyte Adhesion To Cerebral Microvascular Endothelial Cells In Vitro., Chris Blom, Brittany L Deller, Douglas D Fraser, Eric K Patterson, Claudio M Martin, Bryan Young, Patricia C Liaw, Payam Yazdan-Ashoori, Angelica Ortiz, Brian Webb, Greg Kilmer, David E Carter, Gediminas Cepinskas

Medical Biophysics Publications

INTRODUCTION: Sepsis-associated encephalopathy (SAE) is a state of acute brain dysfunction in response to a systemic infection. We propose that systemic inflammation during sepsis causes increased adhesion of leukocytes to the brain microvasculature, resulting in blood-brain barrier dysfunction. Thus, our objectives were to measure inflammatory analytes in plasma of severe sepsis patients to create an experimental cytokine mixture (CM), and to use this CM to investigate the activation and interactions of polymorphonuclear leukocytes (PMN) and human cerebrovascular endothelial cells (hCMEC/D3) in vitro.

METHODS: The concentrations of 41 inflammatory analytes were quantified in plasma obtained from 20 severe sepsis patients and …

Face And Content Validity Of A Novel, Web-Based Otoscopy Simulator For Medical Education., Brandon Wickens, Jordan Lewis, David P Morris, Murad Husein, Hanif M Ladak, Sumit K Agrawal

Medical Biophysics Publications

BACKGROUND: Despite the fact that otoscopy is a widely used and taught diagnostic tool during medical training, errors in diagnosis are common. Physical otoscopy simulators have high fidelity, but they can be expensive and only a limited number of students can use them at a given time.

OBJECTIVES: 1) To develop a purely web-based otoscopy simulator that can easily be distributed to students over the internet. 2) To assess face and content validity of the simulator by surveying experts in otoscopy.

METHODS: An otoscopy simulator, OtoTrain™, was developed at Western University using web-based programming and Unity 3D. Eleven experts from …

Respective And Combined Effects Of Impairments In Sensorimotor Systems And Cognition On Gait Performance: A Population-Based Cross-Sectional Study., Olivier Beauchet, Cyrille P Launay, Bruno Fantino, Gilles Allali, Cédric Annweiler

Medical Biophysics Publications

BACKGROUND: Respective and combined effects of impairments in sensorimotor systems and cognition on gait performance have not been fully studied. This study aims to describe the respective effects of impairments in muscle strength, distance vision, lower-limb proprioception and cognition on the Timed Up & Go (TUG) scores (i.e., performed TUG [pTUG], imagined TUG [iTUG] and the time difference between these two tests [delta TUG]) in older community-dwellers; and to examine their combined effects on TUG scores.

METHODS: Based on a cross-sectional design, 1792 community-dwellers (70.2±4.8 years; 53.6% female) were recruited. Gait performance was assessed using pTUG, iTUG and delta TUG. …

A Method For 3d Histopathology Reconstruction Supporting Mouse Microvasculature Analysis., Yiwen Xu, J Geoffrey Pickering, Zengxuan Nong, Eli Gibson, John-Michael Arpino, Hao Yin, Aaron D Ward

Medical Biophysics Publications

Structural abnormalities of the microvasculature can impair perfusion and function. Conventional histology provides good spatial resolution with which to evaluate the microvascular structure but affords no 3-dimensional information; this limitation could lead to misinterpretations of the complex microvessel network in health and disease. The objective of this study was to develop and evaluate an accurate, fully automated 3D histology reconstruction method to visualize the arterioles and venules within the mouse hind-limb. Sections of the tibialis anterior muscle from C57BL/J6 mice (both normal and subjected to femoral artery excision) were reconstructed using pairwise rigid and affine registrations of 5 µm-thick, paraffin-embedded …

Magnetic Resonance Imaging Biomarkers Of Chronic Obstructive Pulmonary Disease Prior To Radiation Therapy For Non-Small Cell Lung Cancer., Khadija Sheikh, Dante P I Capaldi, Douglas A Hoover, David A Palma, Brian P Yaremko, Grace Parraga

Medical Biophysics Publications

OBJECTIVE: In this prospectively planned interim-analysis, the prevalence of chronic obstructive lung disease (COPD) phenotypes was determined using magnetic resonance imaging (MRI) and X-ray computed tomography (CT) in non-small-cell-lung-cancer (NSCLC) patients.

MATERIALS AND METHODS: Stage-III-NSCLC patients provided written informed consent for pulmonary function tests, imaging and the 6-min-walk-test. Ventilation defect percent (VDP) and CT lung density (relative-of-CT-density-histogram

RESULTS: Seventeen stage-III NSCLC patients were evaluated (68 ± 7 years, 7 M/10 F, mean FEV1 = 77%pred) including seven current and 10 ex-smokers and eight patients with a prior lung disease diagnosis. There was a significant difference for smoking history (p = …

Deficits In Audiovisual Speech Perception In Normal Aging Emerge At The Level Of Whole-Word Recognition., Ryan A Stevenson, Caitlin E Nelms, Sarah H Baum, Lilia Zurkovsky, Morgan D Barense, Paul A Newhouse, Mark T Wallace

Brain and Mind Institute Researchers' Publications

Over the next 2 decades, a dramatic shift in the demographics of society will take place, with a rapid growth in the population of older adults. One of the most common complaints with healthy aging is a decreased ability to successfully perceive speech, particularly in noisy environments. In such noisy environments, the presence of visual speech cues (i.e., lip movements) provide striking benefits for speech perception and comprehension, but previous research suggests that older adults gain less from such audiovisual integration than their younger peers. To determine at what processing level these behavioral differences arise in healthy-aging populations, we administered …

Prevalence Of Increases In Functional Connectivity In Visual, Somatosensory And Language Areas In Congenital Blindness., Lizette Heine, Mohamed A Bahri, Carlo Cavaliere, Andrea Soddu, Steven Laureys, Maurice Ptito, Ron Kupers

Brain and Mind Institute Researchers' Publications

There is ample evidence that congenitally blind individuals rely more strongly on non-visual information compared to sighted controls when interacting with the outside world. Although brain imaging studies indicate that congenitally blind individuals recruit occipital areas when performing various non-visual and cognitive tasks, it remains unclear through which pathways this is accomplished. To address this question, we compared resting state functional connectivity in a group of congenital blind and matched sighted control subjects. We used a seed-based analysis with a priori specified regions-of-interest (ROIs) within visual, somato-sensory, auditory and language areas. Between-group comparisons revealed increased functional connectivity within both the …

Nicotine Receptors Mediating Sensorimotor Gating And Its Enhancement By Systemic Nicotine., Farena Pinnock, Daniel Bosch, Tyler Brown, Nadine Simons, John R Yeomans, Cleusa Deoliveira, Susanne Schmid

Brain and Mind Institute Researchers' Publications

Prepulse inhibition (PPI) of startle occurs when intensity stimuli precede stronger startle-inducing stimuli by 10-1000 ms. PPI deficits are found in individuals with schizophrenia and other psychiatric disorders, and they correlate with other cognitive impairments. Animal research and clinical studies have demonstrated that both PPI and cognitive function can be enhanced by nicotine. PPI has been shown to be mediated, at least in part, by mesopontine cholinergic neurons that project to pontine startle neurons and activate muscarinic and potentially nicotine receptors (nAChRs). The subtypes and anatomical location of nAChRs involved in mediating and modulating PPI remain unresolved. We tested the …

Prolonged In Vivo Retention Of A Cathepsin D Targeted Optical Contrast Agent In A Mouse Model Of Alzheimer's Disease., Jonatan A Snir, Mojmir Suchy, Keith St Lawrence, Robert H E Hudson, Stephen H Pasternak, Robert Bartha

Brain and Mind Institute Researchers' Publications

BACKGROUND: Cathepsin D (CatD) is a lysosomal protease that is elevated early in Alzheimer's disease (AD). We have previously developed a Targeted contrast agent (CA) to detect CatD activity in vivo, consisting of a magnetic resonance imaging/fluorescent moiety linked to a cell penetrating peptide (CPP) by means of a CatD cleavage site and have demonstrated its uptake in the brain of an AD mouse model.

OBJECTIVE: The purpose of this study was to characterize the in vivo retention of a near infra-red fluorescent dye labeled version of this CA.

METHODS: Six adult C57Bl/6 wild-type mice and six adult 5XFAD transgenic …

High-Field Functional Imaging Of Pitch Processing In Auditory Cortex Of The Cat., Blake E. Butler, Amee J Hall, Stephen G Lomber

Brain and Mind Institute Researchers' Publications

The perception of pitch is a widely studied and hotly debated topic in human hearing. Many of these studies combine functional imaging techniques with stimuli designed to disambiguate the percept of pitch from frequency information present in the stimulus. While useful in identifying potential "pitch centres" in cortex, the existence of truly pitch-responsive neurons requires single neuron-level measures that can only be undertaken in animal models. While a number of animals have been shown to be sensitive to pitch, few studies have addressed the location of cortical generators of pitch percepts in non-human models. The current study uses high-field functional …

Automatic Segmentation Of The Hippocampus For Preterm Neonates From Early-In-Life To Term-Equivalent Age., Ting Guo, Julie L Winterburn, Jon Pipitone, Emma G Duerden, Min Tae M Park, Vann Chau, Kenneth J Poskitt, Ruth E Grunau, Anne Synnes, Steven P Miller, M Mallar Chakravarty

Brain and Mind Institute Researchers' Publications

INTRODUCTION: The hippocampus, a medial temporal lobe structure central to learning and memory, is particularly vulnerable in preterm-born neonates. To date, segmentation of the hippocampus for preterm-born neonates has not yet been performed early-in-life (shortly after birth when clinically stable). The present study focuses on the development and validation of an automatic segmentation protocol that is based on the MAGeT-Brain (Multiple Automatically Generated Templates) algorithm to delineate the hippocampi of preterm neonates on their brain MRIs acquired at not only term-equivalent age but also early-in-life.

METHODS: First, we present a three-step manual segmentation protocol to delineate the hippocampus for preterm …

Are There Right Hemisphere Contributions To Visually-Guided Movement? Manipulating Left Hand Reaction Time Advantages In Dextrals., David P Carey, E Grace Otto-De Haart, Gavin Buckingham, H Chris Dijkerman, Eric L Hargreaves, Melvyn A Goodale

Brain and Mind Institute Researchers' Publications

Many studies have argued for distinct but complementary contributions from each hemisphere in the control of movements to visual targets. Investigators have attempted to extend observations from patients with unilateral left- and right-hemisphere damage, to those using neurologically-intact participants, by assuming that each hand has privileged access to the contralateral hemisphere. Previous attempts to illustrate right hemispheric contributions to the control of aiming have focussed on increasing the spatial demands of an aiming task, to attenuate the typical right hand advantages, to try to enhance a left hand reaction time advantage in right-handed participants. These early attempts have not been …

Stability Of Self-Referent Encoding Task Performance And Associations With Change In Depressive Symptoms From Early To Middle Childhood., Brandon L Goldstein, Elizabeth P Hayden, Daniel N Klein

Brain and Mind Institute Researchers' Publications

Depressed individuals exhibit memory biases on the self-referent encoding task (SRET), such that those with depression exhibit poorer recall of positive, and enhanced recall of negative, trait adjectives (referred to as positive and negative processing biases). However, it is unclear when SRET biases emerge, whether they are stable, and if biases predict, or are predicted by, depressive symptoms. To address this, a community sample of 434 children completed the SRET and a depressive symptoms measure at ages 6 and 9. Negative and positive processing exhibited low, but significant, stability. At ages 6 and 9, depressive symptoms correlated with higher negative, …

Fusion Analysis Of First Episode Depression: Where Brain Shape Deformations Meet Local Composition Of Tissue., Mahdi Ramezani, Purang Abolmaesumi, Amir Tahmasebi, Rachael Bosma, Ryan Tong, Tom Hollenstein, Kate Harkness, Ingrid Johnsrude

Brain and Mind Institute Researchers' Publications

Computational neuroanatomical techniques that are used to evaluate the structural correlates of disorders in the brain typically measure regional differences in gray matter or white matter, or measure regional differences in the deformation fields required to warp individual datasets to a standard space. Our aim in this study was to combine measurements of regional tissue composition and of deformations in order to characterize a particular brain disorder (here, major depressive disorder). We use structural Magnetic Resonance Imaging (MRI) data from young adults in a first episode of depression, and from an age- and sex-matched group of non-depressed individuals, and create …

An Fmri Comparison Of Neural Activity Associated With Recognition Of Familiar Melodies In Younger And Older Adults., Ritu Sikka, Lola L Cuddy, Ingrid S Johnsrude, Ashley D Vanstone

Brain and Mind Institute Researchers' Publications

Several studies of semantic memory in non-musical domains involving recognition of items from long-term memory have shown an age-related shift from the medial temporal lobe structures to the frontal lobe. However, the effects of aging on musical semantic memory remain unexamined. We compared activation associated with recognition of familiar melodies in younger and older adults. Recognition follows successful retrieval from the musical lexicon that comprises a lifetime of learned musical phrases. We used the sparse-sampling technique in fMRI to determine the neural correlates of melody recognition by comparing activation when listening to familiar vs. unfamiliar melodies, and to identify age …

Ego Depletion Interferes With Rule-Defined Category Learning But Not Non-Rule-Defined Category Learning., John P Minda, Rahel Rabi

Brain and Mind Institute Researchers' Publications

Considerable research on category learning has suggested that many cognitive and environmental factors can have a differential effect on the learning of rule-defined (RD) categories as opposed to the learning of non-rule-defined (NRD) categories. Prior research has also suggested that ego depletion can temporarily reduce the capacity for executive functioning and cognitive flexibility. The present study examined whether temporarily reducing participants' executive functioning via a resource depletion manipulation would differentially impact RD and NRD category learning. Participants were either asked to write a story with no restrictions (the control condition), or without using two common letters (the ego depletion condition). …

Early Initiation Of Antiretroviral Therapy Can Functionally Control Productive Hiv-1 Infection In Humanized-Blt Mice, Qingsheng Li, For Yue Tso, Guobin Kang, Wuxun Lu, Yue Li, Wenjin Fan, Zhe Yuan, Christopher J. Destache, Charles Wood

Nebraska Center for Virology: Faculty Publications

Background—Recent reports showed that functional control of HIV-1 infection for a prolonged time is possible by early anti-retroviral therapy (ART); however its underlying mechanism needs to be studied with a suitable animal model. Recently, humanized-BLT (bone marrow, liver and thymus) mouse (hu-BLT) was shown to be an excellent model for studying HIV-1 infection. We thus tested the feasibility of studying functional control of HIV-1 infection using hu-BLT mice.

Methods—Animals in three treatment groups (Rx-6h, Rx-24h, Rx-48h) and untreated group were infected with HIV-1, followed by ART initiation at 6, 24 or 48 hours post-infection and continued daily for two weeks. …

The Role Of Dendritic Cell Subsets And Innate Immunity In The Pathogenesis Of Type 1 Diabetes And Other Autoimmune Diseases, Jeffrey D. Price, Kristin V. Tarbell

Nebraska Center for Virology: Faculty Publications

Dendritic cells (DCs) are key antigen-presenting cells that have an important role in autoimmune pathogenesis. DCs control both steady-state T cell tolerance and activation of pathogenic responses. The balance between these two outcomes depends on several factors, including genetic susceptibility, environmental signals that stimulate varied innate responses, and which DC subset is presenting antigen. Although the specific DC phenotype can diverge depending on the tissue location and context, there are four main subsets identified in both mouse and human: conventional cDC1 and cDC2, plasmacytoid DCs, and monocyte-derived DCs. In this review, we will discuss the role of these subsets in …

Evidence Of Distinctive Structural Alterations That Differentiate Adhd Boys With And Without A Comorbid Reading Disability, Dhruman Dilip Goradia

Wayne State University Dissertations

Attention deficit hyperactivity disorder (ADHD) and reading disability (RD) are neurodevelopmental disorders that often co-occur. Children with ADHD and co-occurring RD (ADHD/+RD) tend to show greater cognitive deficits than children with ADHD alone (ADHD/-RD). However, the extents to which comorbid RD impact structural alteration in children with ADHD have never been investigated. The overall goal of this study was to assess structural alterations in the subcortical, cortical and white matter that may differentiate ADHD/-RD from ADHD/+RD. The general hypothesis was that ADHD/+RD would show extensive alterations in regions implicated in ADHD than ADHD/-RD as well as show additional abnormalities in …

Neural Alterations Influencing Skilled Reading In Adhd: A Task-Based Fmri Study, Brianne Mohl

Wayne State University Dissertations

Attention-Deficit/Hyperactivity Disorder (ADHD) is a heterogeneous, neurodevelopmental disorder which co-occurs often with Reading Disability (RD). ADHD with and without RD consistently have higher inattentive ratings compared with typically developing controls, with co-occurring ADHD and RD (ADHD/+RD) also demonstrating impaired phonological processing. Accordingly, inattention has been associated with greater phonological impairment, though neither the neural correlates of the co-occurring disorders nor the association are well understood from a functional neuroimaging perspective. The goal was to assess to what extent ADHD/+RD differ from ADHD without RD (ADHD/-RD) and typically developing controls (TDC) in functional activation of attention- and reading-related areas during various …

Cerium Oxide Nanoparticles Attenuate Polymicrobial Sepsis Induced Splenic Damage In Male Sprague Dawley Rats, Venkata Vinay Kumar Bandarupalli

Theses, Dissertations and Capstones

Sepsis is a serious life threatening medical emergency which, if not treated properly, oftentimes results in organ failure and death. Current sepsis treatment protocols are largely centered on the use of antibiotics and supportive care. Recent studies have suggested that antibiotics fail to be effective for sepsis treatment when administered during hypo-dynamic phase of sepsis that is usually characterized by the presence of a cytokine storm. As such, there is an urgent need to develop novel therapeutic drugs that target the inflammatory cytokines that are secreted as a result of increased reactive oxygen species. Cerium oxide nanoparticles (CeO2) have been …

Adipose-Derived Mesenchymal Stem Cells Improve Glucose Homeostasis In High-Fat Diet-Induced Obese Mice, Mingjun Cao, Qingjie Pan, Huanshen Dong, Xinxu Yuan, Yang Li, Zhen Sun, Xiao Dong, Hongjun Wang

Pharmacology and Toxicology Publications

Introduction

Effective therapies for obesity and diabetes are still lacking. The aim of this study was to evaluate whether a single intravenous infusion of syngeneic adipose-derived mesenchymal stem cells (ASCs) can reduce obesity, lower insulin resistance, and improve glucose homeostasis in a high-fat diet-induced obese (DIO) mouse model.

Methods

Seven-week-old C57BL/6 mice were fed a high-fat diet for 20 weeks to generate the DIO mouse model. Mice were given a single intravenous infusion of ex vivo expanded syngeneic ASCs at 2 × 10 ⁶ cells per mouse. DIO or CHOW mice injected with saline were used as controls. Body weights, …

Effects Of Menthol On Nicotine Pharmacokinetic, Pharmacology And Dependence In Mice, Sharki D. Alsharari, Justin R. King, Jacob C. Nordman, Pretal P. Muldoon, Asti Jackson, Andy Z. X. Zhu, Rachel F. Tyndale, Nadine Kabbani, M. Imad Damaj

Pharmacology and Toxicology Publications

Although menthol, a common flavoring additive to cigarettes, has been found to impact the addictive properties of nicotine cigarettes in smokers little is known about its pharmacological and molecular actions in the brain. Studies were undertaken to examine whether the systemic administration of menthol would modulate nicotine pharmacokinetics, acute pharmacological effects (antinociception and hypothermia) and withdrawal in male ICR mice. In addition, we examined changes in the brain levels of nicotinic receptors of rodents exposed to nicotine and menthol. Administration of i.p. menthol significantly decreased nicotine’s clearance (2-fold decrease) and increased its AUC compared to i.p. vehicle treatment. In addition, …