Ganglioside changes associated with temporal lobe epilepsy in the human hippocampus

To understand better the molecular and cellular events associated with status epilepticus, a multifaceted analysis has begun on hippocampal tissues therapeutically removed from patients with temporal lobe epilepsy. In this first study, quantitative changes in major ganglioside species are reported, as well as the immunocytochemical localization on the ganglioside G(D3) in epileptic human hippocampus. Although significant variations were found between patients, the pattern of change was consistent when compared to normal values obtained from an autopsied specimen and the literature. Total ganglioside content was reduced in epileptic hippocampi, which was attributable, in part, to pyramidal cell loss found in CA1 and CA3. In each case, the percentage of ganglioside G(D3) was increased significantly, while ganglioside G(D1a) decreased. The former change is probably associated with reactive astrocytosis and the latter with loss of neuronal dendrites. Immunocytochemical localization revealed G(D3) in the stratum radiatum and the subgranular layer of the dentate gyrus. In these areas, G(D3) was present in punctate structures and astrocytes. These findings indicate that G(D3) increased in selected areas of the sclerotic hippocampus and is presumably related to localized accumulation of reactive glial cells. Since gangliosides have a high affinity for calcium and localized increase in extracellular calcium could disrupt normal neuronal function, the localized increase in G(D3) may not only denote reactive glial cells but may contribute directly to the altered, hyperexcitable condition of epilepsy.