Abstracts

Rationale: Inflammatory cells and various types of antibodies have been described and anti-inflammatory therapies proven successful in treating a number of epilepsies. Autoimmune epilepsies are associated with the presence of antibodies targeting neurons, but IgG treatments are often effective in treating these patients and patients with other forms of epilepsy. Evidence has shown that non-specific IgGs extravasate into brain from blood and enter neurons and glia. However, the significance of IgGs in brain extracellular or intracellular compartments is not well defined. We tested the hypotheses that non-specific IgGs are neuroprotective in an animal model of status epilepticus (SE) and in vitro. Methods: NZBWF1/J mice were injected with 170 mg/kg of pilocarpine, monitored using video-EEG for two hours and then sacrificed. A group of mice were given IP immunoglobulin's prior to pilocarpine injection. Brain, blood and spleens were collected and processed for immunohistochemistry, flow cytometry and ELISA. In vitro experiments were conducted using human dopaminergic neurons exposed to 1% human serum for 16 hours. Results: Exposure of cultured human neurons to IgGs resulted in cellular uptake but no measurable toxicity. In pilocarpine-treated mice, the presence of IgG in neurons correlated with cell survival. Serum levels of IgGs at time of challenge with pilocarpine correlated with reduced post-SE mortality (p<0.05). Exogenous administration of IgGs prevented the development of SE in 75% compared to 25% in untreated mice (p<0.05). Cytotoxic CD8+ T lymphocytes spleen levels at time of pilocarpine correlated with increased severity of SE as did CD 4+ cells. B cells correlated positively with seizure latency. Conclusions: We have demonstrated the anti-seizure effects of endogenous and exogenous non-specific IgGs. Intracellular accumulation of IgG does not cause neuronal cell death after SE or in vitro. In conclusion, BBB leakage and subsequent intracellular localization of IgG may be a mechanism of the anti-seizure effects of non-specific IgG to treat seizures.