UNDERLYING MECHANISMS OF EPILEPSY pptx

UNDERLYING MECHANISMS OF EPILEPSY Edited by Fatima Shad Kaneez Underlying Mechanisms of Epilepsy Edited by Fatima Shad Kaneez Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2011 InTech All chapters are Open Access articles distributed under the Creative Commons Non Commercial Share Alike Attribution 3.0 license, which permits to copy, distribute, transmit, and adapt the work in any medium, so long as the original work is properly cited. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published articles. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book. Publishing Process Manager Dragana Manestar Technical Editor Teodora Smiljanic Cover Designer Jan Hyrat Image Copyright Mairamut, 2011. Used under license from Shutterstock.com First published September, 2011 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechweb.org Underlying Mechanisms of Epilepsy, Edited by Fatima Shad Kaneez p. cm. ISBN 978-953-307-765-9 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface IX Part 1 Causes and Types of Epilepsy 1 Chapter 1 Histopathological Changes in Temporal Epilepsy 3 Assaad Fawaz and Al Khani Raydeh Chapter 2 The Role of Astrocytes in Epileptogenesis 19 Jesús Pastor and Rafael G. Sola Chapter 3 START Proteins in Epilepsy 45 Sang Pil Yoon Chapter 4 Introduction of a Novel Molecular Mechanism of Epilepsy Progression: Roles of Growth Hormone Signaling in a Mouse Model of Temporal Lobe Epilepsy 63 Keiko Kato Chapter 5 Bridging the Gap – Understanding the Role of Gap Junctions in Seizures 77 Logan J. Voss, Gregory Jacobson and Jamie W. Sleigh Part 2 Underlying Mechanisms 99 Chapter 6 Recombinant Laforin for Structural Studies 101 Pedro Castanheira, Susana Moreira, Margarida Casal, Miguel Gama and Carlos Faro Chapter 7 Temporal Lobe Epilepsy: Cell Death and Molecular Targets 117 Maria José da Silva Fernandes, Esper Abrão Cavalheiro, João Pereira Leite and Daniele Suzete Persike VI Contents Chapter 8 The Cross-Talk Between Mitochondria and the Nucleus in the Response to Oxidative Stress Associated with Mitochondrial Dysfunction in Mitochondrial Encephalomyopathies 135 Yu-Ting Wu, Wan-Yu Lee, Shi-Bei Wu and Yau-Huei Wei Chapter 9 Ghrelin Regulation in Epilepsy 151 Flavia Prodam, Simonetta Bellone, Roberta Ricotti, Giulia Genoni, Marina Caputo and Gianni Bona Chapter 10 Regulation of GluR6-PSD95-MLK3 Signaling in KA-Induced Epilepsy 181 Chong Li and Guang-Yi Zhang Chapter 11 Biophysical Aspects of the Nonsynaptic Epileptiform Activity 189 Antônio-Carlos G. Almeida, Antônio M. Rodrigues, Mário A. Duarte, Gilcélio da Silveira, Fulvio A. Scorza, Ricardo M. Arida, Jaderson C. Costa and Esper A. Cavalheiro Chapter 12 A Tale of Two Epiphenomena: The Complex Interplay of Epigenetics and Epilepsy 219 Stacey Beth Foti and A. Jane Roskams Chapter 13 Multimodal MRI Evaluation in Intractable Epilepsy with Pathologically Confirmed Mesial Temporal Sclerosis 241 Jai Jai Shiva Shankar Part 3 Therapeutic Regimes and Side Effects 249 Chapter 14 The Gingival Fibromatoses 251 Sofia Douzgou and Bruno Dallapiccola Chapter 15 Experimental Epilepsy Models and Morphologic Alterations of Experimental Epilepsy Models in Brain and Hippocampus 268 Ilgaz Akdogan and Nilufer Goksin Yonguc Chapter 16 Two Types of Epilepsy Models and Processes of Cognition: Pentylenetetrazole Kindling and Absence Epilepsy of WAG/Rij Rats Strain 283 A. S. Bazyan Chapter 17 Monoamines and Sleep: Effects of Oxcarbazepine 303 Alfonso Alfaro-Rodríguez, Emilio Arch-Tirado and Rigoberto González-Piña Chapter 18 Medicinal Herbs and Epilepsy: A Two Edged Sword 317 Mahyar Janahmadi, Sahar Farajnia, Zahra Ghasemi and Ali Rastqar Contents VII Chapter 19 In-situ Release of Antiepileptic Drugs from Nanostructured Reservoirs 333 Tessy Lopez, Anna Kozina, Emma Ortiz-Islas, Karla A. Espinoza and Richard Gonzalez Chapter 20 Quality of Life and Psychiatric Aspects in Epilepsy 347 Ayşe Kutlu and Halil Ünalan Preface Approximately 1 out of 120 people have epilepsy and 2 out of every 3 new cases are found in developing countries. Young children and people over the age of 65 are more susceptible to epilepsy; however, it can occur to any one at any time in life. Although around 5% of the total world population have seizures, only 0.9% are diagnosed with epilepsy so it is very important to understand the differences between seizures and epilepsy and also to identify the factors responsible for its etiology in order to have more effective therapeutic regime. This book presents twenty chapters ranging from causes and underlying mechanisms to treatment and side effects of epilepsy. This introductory part offers merely a brief skim through some of these quite interesting multidisciplinary chapters. The chapter entitled “Histopathological Changes in Temporal Epilepsy” is an interesting review on the etiology of drug resistant epilepsy. In this paper, authors discuss the dual pathology of epilepsy in association with other alterations due to neuronal injury and loss. Authors offer a hypothesis that the presence of an epileptogenic foci provokes a process of progressive damage of the nervous tissue and result in drug resistant epilepsy. Next chapter, entitled “The Role of Astrocytes in Epileptogenesis” is a review about how astrocytes modulate different types of partial seizure. Authors discuss the pivotal role of astrocytes in epilepsy and their involvement in: managing the trafficking of substances between capillary vessels and neurons, homeostasis of ions, principally potassium (K+), and their role in the metabolism of the brain through the degradation of both glucose and glutamate. In addition, they discuss the release of gliotransmitters, and multiple contacts of cortical astrocytes. They also debate on how astrocytic integration can affect the function of several groups of neurons or synapses, thus working in a more coherent model. Any change in astrocytic physiology changes the equilibrium between neuronal excitation and inhibition leading to epileptogenesis. Further on, the chapter “START proteins in Epilepsy” is based on the observations that the release of neuroactive steroids impairs neuronal survival in the hippocampus. In this chapter, various molecules including steroidogenic acute regulatory protein (StAR)-related lipid transfer domain-containing proteins (START proteins) and their relationship with neurosteroidogenesis were reviewed for further understanding of X Preface their role in epilepsy. The START domain that operates as a lipid exchange unit is suggested for further studies as to elucidate the exact nuclear roles of StarD6 on neurosteroidogenesis with StAR in the nervous system. “Introduction of a novel molecular mechanism on epilepsy progression: roles of growth hormone signaling in a mouse model of temporal lobe epilepsy” is a chapter on epilepsy with foci and the candidate molecules involved in refractory epilepsy. Up- regulation of growth hormones found to have occurred during the process, and metabolic regulation by GH-signaling appears to be responsible for initiating the after discharge threshold during epileptogenesis. “Role of gap junctions and connexion proteins in the mechanism of seizures” is a paper with reference to the connexion proteins, resultant hemichannels, and the association of two hemichannels on neighboring cells to form a gap junction. Literature suggested a deep and multifaceted relationship between gap junction regulation and seizure susceptibility. In this chapter authors have sought to bring together research from a wide range of disciplines encompassing electrophysiology, molecular biology and mathematical modeling, with the aim of addressing the role of gap junctions in the mechanism of seizures. Chapter “Recombinant Laforin for Structural Studies” is about autosomal recessive Lafora disease, also known as progressive myoclonic epilepsy. This type of epilepsy is caused by the mutations in two genes: EPM2A gene, coding for the protein laforin, and NHLRC1 gene, for the protein malin. Focusing on Laforin and its involvement in Lafora disease, authors reported it as therapeutic contender for myoclonic epilepsy as well as a novel candidate for biotechnological applications of carbohydrate binding proteins. “The Cross-talk between Mitochondria and the Nucleus in the Response to Oxidative Stress Associated with Mitochondrial Dysfunction in Mitochondrial Encephalomyopathies” is an interesting review combined with author’s own work. In this review authors discussed the biochemical consequences of mitochondrial dysfunction-elicited oxidative stress, mitochondrial retrograde signaling and regulation of Ca 2+ homoeostasis in neuronal excitability and resultant epileptic seizures. They also discussed the role of stress responsive gene, Sirt1, in the signaling pathway of the cross-talk between mitochondria and the nucleus. “Temporal Lobe Epilepsy (TLE): molecular targets and cell death” is about TLE and other molecular mechanisms involved in the process of cell death. Authors also explored Bcl-2 gene family and their levels in the hippocampus of patients with intractable seizures. In this paper authors have nicely demonstrated that Caspase- mediated inflammatory process could be a potential mechanism for the pathogenesis of TLE and Caspase inhibitors may act as novel therapeutic agents. “Ghrelin regulation in epilepsy” is a review discussing whether hormonal changes in relation to epilepsy are due to seizures activity per se or to consequential effects of [...]... amount of the released drug One of the main prospects of the study is to achieve better protection ’in vivo’ for longer time Also, one needs to find a correlation between the drug release ’in vitro’ and its effect and release profile ’in vivo’ In short, this book contains a range of proposals regarding causes mechanisms and treatment options of epilepsy which will be of interest to a number of scientists... Prof Dr Fatima Shad Kaneez Human Physiology, PAP RSB Institute of Health Sciences University Brunei Darussalam The State of Brunei Darussalam XIII Part 1 Causes and Types of Epilepsy 1 Histopathological Changes in Temporal Epilepsy Assaad Fawaz and Al Khani Raydeh Damascus University/Faculty of medicine Syria 1 Introduction A wide variety of lesions have been reported in the different studies of epilepsy. .. Boison, 2008) The progression of epileptogenesis to chronic epilepsy often leads to pharmacoresistance and affects up to 30% of all patients with epilepsy, particularly those with TLE (Engel, 2001) A wide range of brain injuries and brain lesions are associated with an increased risk of epilepsy In fact, such symptomatic etiologies account for 30-49% of all unprovoked seizures and epilepsy (Herman, 2002)... induced model “Two types of epilepsy models and processes of cognition” is a review in which author presents literature and her own data for the comparison of two types of epileptic activities that is the convulsive epilepsy induced by pentilenetetrazole (PTZ) kindling in Wister rats and non-convulsive absence epilepsy in WAG/Rij rats The main difference between these two types of epilepsy was described... found with high percentages in some series, where most of the glioneuronal tumors were 8 Underlying Mechanisms of Epilepsy Fig 5 The dentate gyrus and the four sectors of ammon’s horn (cresyl violet stain; Armstrong et al, 2007) Fig 6 Cluster of injured vacuolated neurons (HE stain) Histopathological Changes in Temporal Epilepsy Fig 7 Cluster of injured neurons revealing variation in sizes, vacuolization,... et al, 1999) In a studied series of refractory epilepsy, signs of metabolic disorders were noted in all of the cases (Al Khani & Assaad, 2008) Fig 14 Vacuolization of the glial cells in the temporal lobe and hippocampus (HE stain) 2.8 Northern epilepsy Other authors found intraneuronal accumulation of cytoplasmic autofluorescent granules in which is called as northern epilepsy (Herva et al, 2000) 2.9... questions regarding epilepsy and the studies performed by using experimental models can only explore the basic mechanisms of that particular type of epilepsy Some chemicals can induce more than one type of epilepsy model For example crystallized penicillin can induce simple partial, generalized myoclonic, generalized tonic-clonic and generalized absence epilepsy when given using different routes of administration... disorganization of the cortex with cortical laminar disruption, gyral fusion, clusters of atypical neurons and glial cells within the cortex, malalignment of neurons, neuronal cytomegaly, increased numbers of molecular layer neurons, the presence of large neurons displaying a pyramidal or round shape, ballooned cells, and a high concentration of neurofilaments in giant neurons and of glial intermediate... and multifocality of lesions are well documented, reinforcing the hypothesis that the presence of an epileptogenic focus provokes a process of progressive damage of the nervous tissue The good understanding of these processes and their sequencing, especially those leading to neuron death and loss, might contribute in the prevention of progression of epileptic seizure and the damage of nervous tissue... for ‘Cryptogenic’ Epilepsy: Histopathology of cortical dysplasia Nature Reviews 16 Underlying Mechanisms of Epilepsy Neurology, Vol.7, No.2, pp 99-108 Accessed on 20 March, 2011 Available from http://www.medscape.com/viewarticle/737007_2 Bernhardt, B.C., Rozen, D.A., Worsley, K.J., et al., (2009) Longitudinal and cross-sectional analysis of atrophy in pharmacoresistant temporal lobe epilepsy Neurology, . UNDERLYING MECHANISMS OF EPILEPSY Edited by Fatima Shad Kaneez Underlying Mechanisms of Epilepsy Edited by Fatima Shad Kaneez. epilepsy and the studies performed by using experimental models can only explore the basic mechanisms of that particular type of epilepsy. Some chemicals can induce more than one type of epilepsy. and release profile ’in vivo’. In short, this book contains a range of proposals regarding causes mechanisms and treatment options of epilepsy which will be of interest to a number of scientists