Abstracts

Rationale:  Saponins and other components of red ginseng are known to have anti-inflammatory effects. The abundance of peripherally derived immune cells in resected epileptic tissue suggests the immune system as a potential target for anti-epileptogenic therapy. Vascular blood brain barrier (BBB) breakdown and chronic inflammation can lower seizure threshold, and initiate and propagate epileptogenesis.   We aim to modify epileptogenesis by modulating immune cell trafficking through parenteral administration of red ginseng in the intrahippocampal kainic acid (IHKA) model of temporal lobe epilepsy (TLE). We quantified brain infiltrating immune cells and detected seizures to determine therapeutic efficacy of red ginseng using continuous video electroencephalogram (vEEG). Methods: Prolonged status epilepticus (SE) was induced  in 6 week old C57BL/6J mice by stereotaxic injection of 150nl of kainic acid (1 mg/ml)  into the right CA3 / dorsal hippocampus (coordinates: AP -1.7, ML -1.7, DV -1.8). Some animals were implanted with both CA1 depth electrodes (AP -1.7, ML -1.0, DV 1.3), and cortical electrodes and monitored for spontaneous recurrent seizures. Following IHKA injection, we treated one group with daily red ginseng (200 mg/kg/day) for 4 weeks (IHKA-RJ, n=7), another group with daily valproic acid  (30 mg/kg/day) for 4 weeks (IHKA-VA, n=7) and the other group with PBS (IHKA-PBS, n=4). We checked cytokines and the pathologic results at D28. Continuous (24h/week) vEEG monitoring was used to verify the existence of nonconvulsive seizures (>270 mv, >20 spikes/10 seconds) on D7, D14, D21 and D28.. Results: Histochemistry analysis of infiltrating lymphocytes and leukocytes in the brain showed that red ginseng administration reduced infiltration of all peripheral immune cells in the brain. By vEEG, IHKA-PBS developed electrographic seizures while only 33% (2/6) IHKA-nano demonstrated electrographic seizures. Conclusions: The increase in cytotoxic and activated T cells, in the hippocampus after the IHKA injection demonstrated the heightened inflammatory milieu after SE prior to occurrence of spontaneous recurrent seizures in this model of TLE. Repeated red ginseng treatments afterIHKA induced-SE decreased immune cell infiltration into the brain and demonstrated a remarkable decrease in electrographic seizure Funding: None