Degree and pattern of calbindin immunoreactivity in granule cells of the dentate gyrus differ in mesial temporal sclerosis, cortical malformation- and tumor-related epilepsies

A loss of calbindin immunoreactivity in granule cells of the hippocampal dentate gyrus is a characteristic feature of temporal lobe epilepsy with hippocampal sclerosis. Whether decreased calbindin expression is unique to the hippocampal sclerosis associated with cryptogenic temporal lobe epilepsy, or also occurs in tumor- or malformation-related epilepsy, is unknown. We show that calbindin immunoreactivity in granule cells has been decreased in epilepsy regardless of its etiology. In cases of cortical malformations or hippocampal sclerosis, calbindin immunoreactivity was undetectable in most granule cells. In tumor-related resections, in patients who had a long history of epileptic seizures, calbindin was detected only in one-third of granule cells. Regardless of etiology, calbindin expression correlated with age of onset and with duration of the epilepsy. In contrast to tumor-induced epilepsy, where calbindin-immunoreactive granule cells were equally distributed in the granule cell layer, in hippocampal sclerosis and malformation-related epilepsy, two-thirds of calbindin-immunoreactive granule cells were located in the outer half and only one-third in the inner half of the layer. Developmentally, granule cells at the border of the molecular layer are ontogenetically the oldest, and those at the border of the hilus are the youngest. The reduction of calbindin immunoreactivity in ontogenetically younger granule cells highlights the deleterious effect of early occurring epilepsy and initial early precipitating injury, including febrile seizures that may substantially affect developing immature granule cells, but less the earlier born matured ones.

Research highlights
► Calbindin expression in granule cells of the dentate gyrus in temporal lobe epilepsy.
► Loss of calbindin in granule cells independently of the etiology of epilepsy.
► Loss of calbindin correlated with the age of onset and the duration of epilepsy.
► Loss of calbindin differs in the developmentally older and younger cells.
► Significance of early initial precipitating injury in epilepsy.