trisialoganglioside-gt1 and Epilepsy

The effects of ganglioside GT1b or melatonin on damage to brain mitochondrial DNA (mtDNA) and seizures induced by kainic acid were investigated both in vivo and in vitro. An intraperitoneal (i.p.) injection of kainic acid (45 mg/kg) produced broad-spectrum limbic and severe sustained seizures in all of the treated mice. These seizures were completely abolished by an intracerebroventricular (i.c.v.) injection of ganglioside GT1b (90 nmol/brain), a potent inhibitor of glutamate receptor mediated activation and translocation of protein kinase C and lipid peroxidation, or an i.p. injection of melatonin (20 mg/kg), a potent scavenger of hydroxyl radicals (*OH). The administration of kainic acid caused damage to mtDNA in brain frontal and central portion of cortex in mice. The damage to mtDNA was abolished by pre-injection of ganglioside GT1b (90 nmol/brain, i.c.v.) or melatonin (20 mg/kg, i.p.). In vitro exposure of kainic acid (0.25, 0.5 or 1.0 mM) inflicted damage to mtDNA in a concentration-dependent manner. The damage to mtDNA induced by 1.0 mM kainic acid was attenuated by the co-treatment with 60 microM ganglioside GT1b or 1.5 mM melatonin. Furthermore, kainic acid (0.5 or 1.0 mM) increased lipid peroxidation in a concentration-dependent manner when incubated with a homogenate prepared from mice brain at 37 degrees C for 20 or 60 min. However, the increased lipid peroxidation was completely abolished by the co-treatment with ganglioside GT1b (60 microM) or melatonin (1.5 mM). These results suggest that reactive oxygen species including hydroxyl radical (*OH) may play a role in the damage to brain mtDNA and seizures induced by kainic acid. We conclude that the preventive effect of melatonin or ganglioside GT1b against kainic acid-induced mtDNA damage or seizures may be due to its scavenging of reactive oxygen species including the *OH.

Topics: Animals; Brain; Cell Death; DNA Damage; DNA, Mitochondrial; Dose-Response Relationship, Drug; Drug Interactions; Epilepsy; Free Radicals; Gangliosides; Kainic Acid; Male; Melatonin; Mice; Mitochondria; Neurons; Oxidative Stress

The role of antiganglioside antibodies (AGAs) in late post-apoplectic epilepsy (LPAE) was studied. Serum AGAs from 8 patients with large lobar infarctions were serially checked for 2.5 months. Sera from another 30 patients with fronto-temporoparietal (FTP) or frontal (F) infarction were obtained 3 months to 3 years after a stroke for AGA analysis. These 30 patients were followed up for 3 years following their strokes to determine if LPAE developed. Results showed that 7/8 patients with large lobar infarction showed increase in either anti-GT1b or anti-GM1 (IgM or IgG) within a few weeks, but levels returned to the baseline 2-3 months after stroke. LPAE occurred in 9/21 patients with FTP infarction and 5/9 with F infarction. There was no difference in AGAs among patients with FTP and F infarctions. Pooled data from these 2 groups showed no correlation between AGAs and LPAE. These data document for the first time that anti-GT1b and anti-GM1 antibodies can transiently increase after stroke, but their late titers are not associated with LPAE.

Topics: Adult; Aged; Aged, 80 and over; Antibodies; Cerebrovascular Disorders; Epilepsy; G(M1) Ganglioside; Gangliosides; Humans; Middle Aged