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Title	Theiler's virus encephalopathy: a novel model of epilepsy
Publication Type	dissertation
School or College	College of Health
Department	Neuroscience Program
Author	Stewart, Kerry-Ann A.
Date	2009
Description	Epilepsy is a devastating neurological disorder characterized by recurrent seizures and affecting approximately 50 million people worldwide. Viral infections of the central nervous system are associated with an increased risk for the development of seizures and epilepsy. However, there is currently no available animal model of viral infectioninduced epilepsy. The studies presented in this dissertation were designed to test the hypothesis that Theiler's virus (TMEV) infection of C57BL/6 (B6) mice induces structural damage associated with persistent hyperexcitability, altered seizure susceptibility, and epilepsy postinfection. Completing the following specific aims tested this hypothesis. Specific Aim 1 (a) identified brain regions involved in acute TMEV-induced seizures, and (b) assessed the impact of TMEV- infection on chronic electroconvulsive seizure thresholds and corneal kindling acquisition rates. The results suggest that limbic and forebrain regions, including the hippocampus and the thalamus, are activated during acute spontaneous seizures. Mice that display symptomatic seizures during the acute infection exhibited increased rates of kindling acquisition and reduced thresholds to stimuli activating limbic and forebrain structures. Confirming the importance of genetic background in TMEV-induced seizure susceptibility, comparable studies in SJL/J did not reveal reduced seizure thresholds. Specific Aim 2 examined seizure progression and chronic histopathology TMEV-infected B6 mice to determine the incidence of postinfection epilepsy. Continuous video-electroencephalogram monitoring demonstrated that a significant proportion of infected B6 mice display symptomatic seizures during the acute infection. Following a latent period, a majority of these mice subsequently developed epilepsy. Histopathological studies indicated chronic structural and cellular abnormalities In . epileptic TMEV-infected B6 mice, including significant hippocampal sclerosis. Together, these findings establish TMEV-infected B6 mice as a novel preclinical model of infection-induced epilepsy. It is anticipated that the data presented in this dissertation will provide a framework for future studies aimed at elucidating the mechanism(s) of postinfection epilepsy and identifying therapies for treating and/or preventing epilepsy in the clinical setting.
Type	Text
Publisher	University of Utah
Dissertation Name	Doctor of Philosophy
Language	eng
Rights Management	© Kerry- Ann A. Stewart
Format	application/pdf
Format Medium	application/pdf
ARK	ark:/87278/s6j17746
Setname	ir_etd
ID	2564095
Reference URL	https://collections.lib.utah.edu/ark:/87278/s6j17746

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Title	Page 24
Format	application/pdf
Setname	ir_etd
ID	2564119
OCR Text	Show 14 Jutila L, Immonen A, Partanen K, Partanen J, Mervaala E, Ylinen A, AlafuzoffI, Paljarvi L, Karkola K, Vapalahti M, Pitkanen A (2002) Neurobiology of epileptogenesis in the temporal lobe. Adv Tech Stand Neurosurg 27:5-22. Karhunen H, Jolkkonen J, Sivenius J, Pitkanen A (2005) Epileptogenesis after experimental focal cerebral ischemia. Neurochem Res 30:1529-1542. Kellinghaus C, Engbring C, Kovac S, Moddel G, Boesebeck F, Fischera M, Anneken K, Klonne K, Reichelt D, Evers S, Husstedt IW (2008) Frequency of seizures and epilepsy in neurological HIV-infected patients. Seizure 17:27-33. Kimiagar I, Pollak L, Gandelman- Marton R, Itzhaki A, Milo R, Rabey JM (2002) Neurological features of West Nile virus infection during the 2000 outbreak in a regional hospital in Israel. J Neurol Sci 200:63-66. Klein C, Lehrmann E, Guidetti P, Love A, Williamson J, Bertram EH, Schwarcz R (2008) Glial activation precedes seizures and hippocampal neurodegeneration in measles virus infected mice. Epilepsia 49 Suppl2: 13-23. Libbey JE, Kirkman NJ, Smith MC, Tanaka T, Wilcox KS, White HS, Fujinami RS (2008) Seizures following picornavirus infection. Epilepsia 49: 1066-1074. Lipton HL (1978) The relatonship of Theiler's mouse encephalomyelitis virus plaque size with persistent infection. In: Persistent Viruses: ICN-UCLA Symposia on Molecular and Cellular Biology (Stevens JT, G. J.; and Fox, C. F., ed), pp 679689. New York: Academic Press, Inc. Lipton HL, Calenoff M, Bandyopadhyay P, Miller SD, Dal Canto MC, Gerety S, Jensen K (1991) The 5' noncoding sequences from a less virulent Theiler's VIruS dramatically attenuate GDVII neurovirulence. J ViroI65:4370-4377. Lukasiuk K, Pitkanen A (2004) Large-scale analysis of gene expression in research: is synthesis already possible? Neurochem Res 29: 1169-1178. epilepsy Lukasiuk K, Dabrowski M, Adach A, Pitkanen A (2006) Epileptogenesis-related genes revisited. Prog Brain Res 158:223-241. Mewasingh L (2006) Febrile seizures. Clin Evid:415-422. Misra UK, Kalita J (2001) Seizures in Japanese encephalitis. J Neurol Sci 190:57-60. Misra UK, Kalita J, Nair PP (2008) Status epilepticus in central nervous system infections: an experience from a developing country. Am J Med 121:618-623. Monteyne P, Bureau JF, Brahic M (1997) The infection of mouse by Theiler's virus: from genetics to immunology. Immunol Rev 159: 163-176.
Reference URL	https://collections.lib.utah.edu/ark:/87278/s6j17746/2564119