碩士 / 國立成功大學 / 藥理學研究所 / 90 / 英文摘要
(Abstract in English)
Epilepsy is a chronic disorder characterized by recurrent self-limited seizures with excessive discharges throughout localized or generalized groups of neurons in the brain. Recurrent seizures, if frequent, interfere with the patients’ ability to perform day-to-day activities; however, judicious use of antiepileptic medications allows about 65-70% of epileptic patients to be seizure-free. It means that about 25-30% of epileptic patients can’t be cured by classical antiepileptic drugs. This type of drug-resistant epilepsy is called “intractable epilepsy”. However, the consequences and the underlying mechanisms of the generation of intractable epilepsy remain unclear. Recently, clinical observations have described the detection of herpes simplex virus (HSV) in the brain in patients who presented with intractable seizures. It is therefore hypothesized that seizure activity in a subset of epilepsy cases is caused by persistent HSV infection in the seizure foci. To elucidate the role of HSV infection in the development of chronic seizure disorders and the possible epileptogenic mechanisms, we have developed an in vitro organotypic slice culture model of epileptic seizures induced by persistent HSV type 1 (HSV-1) infection and use electrophysiological recordings and immunohitochemistry techniques. Intracellular and extracellular recordings revealed that HSV-1 infection may successfully induce epileptiform discharge pattern on the slice culture in the CA3 region. The postinfected CA3 pyramidal cells exhibited a more depolarizing resting membrane potential concomitanted with an increase in the membrane input resistance, and had an reduction in the amplitude of afterhyperpolarization amplitude and a marked decrease in the GABAB-mediated inhibition. In contrast, the excitatory synaptic transmission in the hippocampal CA3 region did not significantly change. Besides electrophysiological recordings, we also checked HSV-1 distribution, neuron morphological change, and mossy fiber sprouting on cultured slices using immunohistochemistry, Nissl stain, and Timm stain respectively. Accidently, we found that the hippocampal CA3 neurons didn’t present neuronal activities after 7 days HSV-1 infection. We suggested that it may be due to the global neuronal death after chronic HSV-1 infection. In final set of experiment, we cultured the slices in the presence of acyclovir (20 mM) to inhibit HSV-1 replication and found that most CA3 neurons recorded by intracellular recording tended to present stable phenotype. These findings confirmed the hypothesis that HSV-1 continuous replication may cause cell damage. This hypothesis was also confirmed by hematoxylin-eosin staining method. Judging from the characteristics of the electrophysiological correlates, and neuropathology, this chronic slice model has points of resemblance with recent interpretation of the HSV hypothesis for limbic seizures that caused from change of neuron membrane properties and decreased GABAB inhibitory effect, and it may be used to investigate the pathogenesis and therapeutic strategies of human pharmacoresistant epilepsy. Furthermore, HSV-1 infection may injure neurons and eventually lead to neuronal death.
| Identifer | oai:union.ndltd.org:TW/090NCKU5550009 |
| Date | January 2002 |
| Creators | Su-Fen Chen, 陳素芬 |
| Contributors | Kuei-Sen Hsu, 許桂森 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 163 |
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