Medical Neurobiology Commons^™

Trichloroethylene Exposure And Traumatic Brain Injury Interact And Produce Dual Injury Based Pathology And Pioglitazone Can Attenuate Deficits Following Traumatic Brain Injury, Andrew David Sauerbeck

University of Kentucky Doctoral Dissertations

The development of Parkinson's disease (PD) in humans has been linked to genetic and environmental factors for many years. However, finding common single insults which can produce pathology in humans has proved difficult. Exposure to trichloroethylene (TCE) or traumatic brain injury (TBI) has been shown to be linked to PD and it has also been proposed that multiple insults may be needed for disease development.

The present studies show that exposure to TCE prior to a TBI can result in pathology similar to early PD and that the interaction of both insults is required for impairment in behavioral function, and …

Orbitofrontal Cortex Provides Cross-Modal Valuation Of Self-Generated Stimuli, William A. Cunningham, Ingrid J. Haas, Ashley S. Waggoner

Department of Political Science: Faculty Publications

Prior research has shown that the orbitofrontal cortex (OFC) plays an important role in the representation of the evaluation of stimuli, regardless of stimulus modality. Based on these findings, researchers have proposed that the OFC serves a common currency function, allowing for the direct comparison of different types of perceptual stimuli (e.g. food, drink, money). The present study was designed to extend this research and investigate whether these same regions of OFC that have been identified in previous research are involved in evaluating imagined stimuli. Specifically, we asked participants to draw on prior attitudinal knowledge to generate internal representations of …

Genome-Wide Association Studies At The Interface Of Alzheimer’S Disease And Epidemiologically Related Disorders, Christopher Ryan Simmons

University of Kentucky Doctoral Dissertations

Genome-wide association studies (GWAS)s provide an unbiased means of exploring the landscape of complex genetic disease. As such, these studies have identified genetic variants that are robustly associated with a multitude of conditions. I hypothesize that these genetic variants serve as excellent tools for evaluation of the genetic interface between epidemiologically related conditions. Herein, I test the association between SNPs associated with either (i) plasma lipids, (ii) rheumatoid arthritis (RA) or (iii) diabetes mellitus (DM) and late-onset Alzheimer’s disease (AD) to identify shared genetic variants. Regarding the most significantly AD-associated variants, I have also attempted to elucidate their molecular function. …

Functional Connectivity For Configural And Featural Face Processing In The Broad Autism Phenotype, Jonathan Darrell Clark

University of Kentucky Doctoral Dissertations

During normal development, face processing involves a gradual shift from a featurally oriented style to a mature configural style by adolescence. This shift may coincide with increased right hemispheric dominance for faces supporting configural processing. Previous studies suggest that individuals diagnosed with ASD continue to process faces using individual parts and features into adulthood. This continued bias may be due to deficits in configural processing abilities. The current study investigated measures of functional connectivity during featural and configural processing of faces in broad autism phenotype sibling (ASD-sibs) children compared to age, sex, and handedness matched normal developing (ND) controls and …

The Effect Of Spiritualism On The Neuropsychological Function Of Memory, Carla Farcello

McNair Poster Presentations

The amount of physiological-neurological research performed over the past few years has dramatically increased due to our ability to view the structure and function of the brain in living human beings. The use of imaging tools has resulted in huge strides forward in unlocking some of the mysteries of the 3 pound universe-the human brain. One of the more unique neural processes being recently addressed is the affect of belief and spiritualism-the sense of being connected to something larger than oneself-on the human brain. This study hypothesized that better memory will be documented among the experimental group who report being …

Awake Vs. Asleep Placement Of Spinal Cord Stimulators: A Cohort Analysis Of Complications Associated With Placement, Steven M. Falowski, Md, Amanda Celii Md, Anthony K. Sestokas Phd, Daniel M. Schwartz Phd, Craig Matsumoto Mpas, Ashwini Sharan Md

Department of Neurosurgery Faculty Papers

Introduction: Patients will typically undergo awake surgery for permanent implantation of SCS in an attempt to optimize electrode placement using patient feedback about the distribution of stimulation-induced paresthesia. The present study compared efficacy of first-time electrode placement under awake conditions with that of neurophysiologically-guided placement under general anesthesia.

Methods: A retrospective review was performed of 387 SCS surgeries among 259 patients which included 167 new stimulator implantation to determine whether first time awake surgery for placement of spinal cord stimulators is preferable to non-awake placement.

Results: The incidence of device failure for patients implanted using neurophysiologically-guided placement under general anesthesia …

Acetate Causes Alcohol Hangover Headache In Rats., Christina R Maxwell, Rebecca Jay Spangenberg, Jan B Hoek, Stephen D Silberstein, Michael L Oshinsky

Department of Neurology Faculty Papers

BACKGROUND: The mechanism of veisalgia cephalgia or hangover headache is unknown. Despite a lack of mechanistic studies, there are a number of theories positing congeners, dehydration, or the ethanol metabolite acetaldehyde as causes of hangover headache.

METHODS: We used a chronic headache model to examine how pure ethanol produces increased sensitivity for nociceptive behaviors in normally hydrated rats.

RESULTS: Ethanol initially decreased sensitivity to mechanical stimuli on the face (analgesia), followed 4 to 6 hours later by inflammatory pain. Inhibiting alcohol dehydrogenase extended the analgesia whereas inhibiting aldehyde dehydrogenase decreased analgesia. Neither treatment had nociceptive effects. Direct administration of acetate …

Ms4a4b, A Cd20 Homologue In T Cells, Inhibits T Cell Propagation By Modulation Of Cell Cycle., Hui Xu, Yaping Yan, Mark S Williams, Gregory B Carey, Jingxian Yang, Hongmei Li, Guang-Xian Zhang, Abdolmohamad Rostami

Department of Neurology Faculty Papers

MS4a4B, a CD20 homologue in T cells, is a novel member of the MS4A gene family in mice. The MS4A family includes CD20, FcεRIβ, HTm4 and at least 26 novel members that are characterized by their structural features: with four membrane-spanning domains, two extracellular domains and two cytoplasmic regions. CD20, FcεRIβ and HTm4 have been found to function in B cells, mast cells and hematopoietic cells respectively. However, little is known about the function of MS4a4B in T cell regulation. We demonstrate here that MS4a4B negatively regulates mouse T cell proliferation. MS4a4B is highly expressed in primary T cells, natural …

Emergency Reversal Of Antiplatelet Agents In Patients Presenting With An Intracranial Hemorrhage: A Clinical Review, Peter G. Campbell, Md, Anish Sen, Bs, Sanjay Yadla, Md, Pascal Jabbour, Md, Jack Jallo, Md, Phd

Department of Neurosurgery Faculty Papers

Abstract

Objective: Prehospital use of antiplatelet agents has been associated with an increased risk for ICH as well as a secondary increase in ICH volume after the initial hemorrhage. Strategies to reestablish platelet aggregation are used in clinical practice, but without any established guidelines or recommendations. This article serves to evaluate the literature regarding “reversal” of antiplatelet agents in neurosurgical populations.

Methods: PUBMED and MEDLINE databases were searched for publications from 1966 to 2009 relating to intracranial hemorrhage and antiplatelet agents. The reference sections of recent articles, guidelines and reviews were reviewed and pertinent articles identified. Studies were classified by …

Effect Of Acute Administration Of Angiopoietin-1 In Experimental Traumatic Spinal Cord Injury: Magnetic Resonance Imaging And Neurobehavioral Studies, Chirag B. Patel

Dissertations and Theses (Open Access)

Spinal cord injury (SCI) is a devastating condition that affects people in the prime of their lives. A myriad of vascular events occur after SCI, each of which contributes to the evolving pathology. The primary trauma causes mechanical damage to blood vessels, resulting in hemorrhage. The blood-spinal cord barrier (BSCB), a neurovascular unit that limits passage of most agents from systemic circulation to the central nervous system, breaks down, resulting in inflammation, scar formation, and other sequelae. Protracted BSCB disruption may exacerbate cellular injury and hinder neurobehavioral recovery in SCI.

In these studies, angiopoietin-1 (Ang1), an agent known to reduce …

Dopaminergic Neurons Derived From Human Induced Pluripotent Stem Cells Survive And Integrate Into 6-Ohda-Lesioned Rats., Jingli Cai, Ming Yang, Elizabeth Poremsky, Sarah Kidd, Jay S Schneider, Lorraine Iacovitti

Farber Institute for Neuroscience Faculty Papers

Cell replacement therapy could be an important treatment strategy for Parkinson's disease (PD), which is caused by the degeneration of dopamine neurons in the midbrain (mDA). The success of this approach greatly relies on the discovery of an abundant source of cells capable of mDAergic function in the brain. With the paucity of available human fetal tissue, efforts have increasingly focused on renewable stem cells. Human induced pluripotent stem (hiPS) cells offer great promise in this regard. If hiPS cells can be differentiated into authentic mDA neuron, hiPS could provide a potential autologous source of transplant tissue when generated from …

White Matter Diffusion Alterations In Normal Women At Risk Of Alzheimer's Disease, Charles D. Smith, Himachandra Chebrolu, Anders H. Andersen, David A. Powell, Mark A. Lovell, Shuling Xiong, Brian T. Gold

Neurology Faculty Publications

Increased white matter mean diffusivity and decreased fractional anisotropy (FA) has been observed in subjects diagnosed with mild cognitive impairment (MCI) and Alzheimer's disease (AD). We sought to determine whether similar alterations of white matter occur in normal individuals at risk of AD. Diffusion tensor images were acquired in 42 cognitively normal right-handed women with both a family history of dementia and at least one apolipoprotein E4 allele. These were compared with images from 23 normal women without either AD risk factor. Group analyses were performed using tract-based spatial statistics. Reduced FA was observed in the fronto-occipital and inferior temporal …

Q-Ve-Oph, A Negative Control For O-Phenoxy-Conjugated Caspase Inhibitors, Benjamin Southerland, Kashmira Kulkarni-Datar, Chanel Keoni, Rebecca Bricker, William C. Grunwald Jr., Daniel M. Ketcha, Eugene Hern, David R. Cool, Thomas L. Brown

Neuroscience, Cell Biology & Physiology Faculty Publications

The broad-spectrum apoptosis (caspase) inhibitor, Q-VD-OPh, has been shown to have no side effects and is effective at a much lower concentration than other FMK-type caspase inhibitors. However, an appropriate negative control to use with this inhibi- tor has not been available. In this study, we developed and analyzed a new compound, based on the Q-VD-OPh backbone, which acts as a cognate negative control. To create the negative control, we substituted a glutamate residue for the aspartate residue to create Q-VE-OPh, thereby retaining the identical charge and molecular properties with only the addition of an extra –CH2 group. The purity …

Multiport Minimally Invasive Skull Base Surgery: How Many Ports Are Too Many?, Yaron A. Moshel, Theodore H. Schwartz

Department of Neurosurgery Faculty Papers

Surgical access to the ventral skull base has evolved considerably over the past several years with the introduction of minimally invasive endoscopic and endoscope-assisted approaches. The accompanying manuscript by Ciporen et al. demonstrates an addition to this growing body of literature in their description of the feasibility of multiportal endoscopic approaches to the skull base, particularly the precaruncular transorbital approach, in a series of cadaver dissections. Similar to laparoscopic abdominal surgery, which utilizes multiple small ports to improve visualization and manipulation, they envision a modular combination of approaches that allows an endoscope to be placed in one port and surgery …

Characterizing Purkinje Cell Responses And Cerebellar Influence On Fluid Licking In The Mouse, Jeri Lonece Bryant

Theses and Dissertations (ETD)

Rodents consume water by performing stereotypical, rhythmic licking movements which are believed to be driven by central pattern generating circuits located in the brainstem. Temporal aspects of rhythmic licking behavior have been shown to be represented in the olivo-cerebellar system in the form of population complex spike activity. These findings suggest that the olivo-cerebellar system is involved in the generating circuitry responsible for licking rhythm in rodents. However, the representation of licking in the simple spike activity of Purkinje cells and the consequences of loss of cerebellar function on licking behavior has not been quantified. I investigated the influence of …

Occipital Nerve Stimulator Systems: Review Of Complications And Surgical Techniques, Steven Falowski, Dajie Wang, Arvind Sabesan, Ashwini Sharan

Department of Neurosurgery Faculty Papers

Introduction: Stimulation of the occipital nerves is becoming more widely accepted in the treatment of occipital neuritis and migraine disorders.

Objective: Presently, equipment available for spinal cord stimulation is adapted for insertion into the subcutaneous space over the occipital nerves. Many technical factors need to be reassessed to optimize the therapy.

Methods: We performed a retrospective review of patients implanted from 2003 to 2007 at a single center. We aimed to analyze the rate of surgical complications related to implantation technique. A total of 28 patients were present for analysis. Patients were followed up to 60 months with a mean …

Acat1 Gene Ablation Increases 24(S)-Hydroxycholesterol Content In The Brain And Ameliorates Amyloid Pathology In Mice With Ad, Elena Y. Bryleva, Maximillian A. Rogers, Catherine C. Y. Chang, Floyd Buen

Dartmouth Scholarship

Cholesterol metabolism has been implicated in the pathogenesis of several neurodegenerative diseases, including the abnormal accumulation of amyloid-beta, one of the pathological hallmarks of Alzheimer disease (AD). Acyl-CoA:cholesterol acyltransferases (ACAT1 and ACAT2) are two enzymes that convert free cholesterol to cholesteryl esters. ACAT inhibitors have recently emerged as promising drug candidates for AD therapy. However, how ACAT inhibitors act in the brain has so far remained unclear. Here we show that ACAT1 is the major functional isoenzyme in the mouse brain. ACAT1 gene ablation (A1-) in triple transgenic (i.e., 3XTg-AD) mice leads to more than 60% reduction in full-length human …

Progressive Changes In Microglia And Macrophages In Spinal Cord And Peripheral Nerve In The Transgenic Rat Model Of Amyotrophic Lateral Sclerosis, David J. Graber, William F. Hickey, Brent T. Harris

Dartmouth Scholarship

The role of neuroinflammation in motor neuron death of amyotrophic lateral sclerosis (ALS) is unclear. The human mutant superoxide dismutase-1 (hmSOD1)-expressing murine transgenic model of ALS has provided some insight into changes in microglia activity during disease progression. The purpose of this study was to gain further knowledge by characterizing the immunological changes during disease progression in the spinal cord and peripheral nerve using the more recently developed hmSOD1 rat transgenic model of ALS. Using immunohistochemistry, the extent and intensity of tissue CD11b expression in spinal cord, lumbar nerve roots, and sciatic nerve were evaluated in hmSOD1 rats that were …

Bitc Sensitizes Pancreatic Adenocarcinomas To Trail-Induced Apoptosis, Christina A. Wicker, Ravi P. Sahu, Kashmira Kulkarni-Datar, Sanjay K. Srivastava, Thomas L. Brown

Neuroscience, Cell Biology & Physiology Faculty Publications

Pancreatic adenocarcinoma is an aggressive cancer with a greater than 95% mortality rate and short survival after diagnosis. Chemotherapeutic resistance hinders successful treatment. This resistance is often associated with mutations in codon 12 of the K-Ras gene (K-Ras 12), which is present in over 90% of all pancreatic adenocarcinomas. Codon 12 mutations maintain Ras in a constitutively active state leading to continuous cellular proliferation. Our study determined if TRAIL resistance in pancreatic adenocarcinomas with K-Ras 12 mutations could be overcome by first sensitizing the cells with Benzyl isothiocyanate (BITC). BITC is a component of cruciferous vegetables and a cell cycle …

Characterization And Optimization Of Microelectrode Arrays For Glutamate Measurements In The Rat Hippocampus, Pooja Mahendra Talauliker

University of Kentucky Doctoral Dissertations

An overarching goal of the Gerhardt laboratory is the development of an implantable neural device that allows for long-term glutamate recordings in the hippocampus. Proper L-glutamate regulation is essential for hippocampal function, while glutamate dysregulation is implicated in many neurodegenerative diseases. Direct evidence for subregional glutamate regulation is lacking in previous in vivo studies because of limitations in the spatio-temporal resolution of conventional experimental techniques. We used novel enzyme-coated microelectrode arrays (MEAs) for rapid measurements (2Hz) of extracellular glutamate in urethane-anesthetized rats. Potassium-evoked glutamate release was highest in the cornu ammonis 1 (CA1) subregion and lowest in the cornu ammonis …