PHD, Kent State University, 2015, College of Arts and Sciences / School of Biomedical Sciences

Many types of epilepsy, autoimmune or otherwise, are associated with the presence of autoantibodies against neuronal proteins. Paradoxically, antibodies (IVIg) have also been used to treat epilepsy. The goals of this research were twofold: 1) Determine the CNS location of antibodies in patients with non-autoimmune epilepsies and the targets of these antibodies; and 2) Examine the effects of endogenous and exogenous specific and non-specific antibodies in two status epilepticus (SE) models Immunohistochemistry and Western blotting were used to localize antibodies in patients with epilepsy, multiple sclerosis (MS) and arteriovenous malformation. Further analysis by ELISA, HEp-2 assay and immunoprecipitation revealed antibody targets. In mouse model experiments, lupus-prone or C57B6/J mice were injected with pilocarpine or kainic acid and monitored by EEG. Mice were treated with IV or IP injection of native or denatured IgGs, at time of or 12 hours before chemoconvulsant. Tissues were processed for immunohistochemistry and ELISA. Brain regions from patients with epilepsy contained extravasated IgGs. Intracellular antibodies were found in epilepsy but not in MS brain. In brain from patients with epilepsy, only neurons displayed nuclear IgGs. All subcellular fractions from brain resections of patients with epilepsy contained extravasated IgGs. In the nuclear IgG pool, anti-histone autoantibodies were identified by two independent methods. Serum analysis revealed anti-histone and anti-chromatin antibodies only in patients with epilepsy. In lupus-prone mice elevated serum IgGs favored post-SE survival. C57B6/J mice injected with native rat IgGs displayed a 40% reduction in pilocarpine-SE compared to control. IgGs extravasated in brains of untreated SE mice, but IgG-treated mice, with no pilocarpine-SE, experienced no parenchymal accumulation of IgGs. IgG leakage was observed in brain samples from KA treated mice and IgG treatment was largely ineffective. These r (open full item for complete abstract)

Committee: Derek Damron Ph.D (Committee Chair); Trine Jorgensen Ph.D (Committee Member); Gary Koski Ph.D (Committee Member); Ernest Freeman Ph.D (Committee Member) Subjects: Biology; Biomedical Research; Cellular Biology; Immunology; Medicine; Neurobiology; Neurosciences