6533b824fe1ef96bd1280a2a

RESEARCH PRODUCT

An increase of hippocampal calretinin-immunoreactive neurons correlates with early febrile seizures in temporal lobe epilepsy

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Numerous studies indicate that initial precipi- tating injuries (IPI) such as febrile seizures during early childhood may play a pivotal role in the pathogenesis of temporal lobe epilepsy (TLE) and Ammon's horn sclero- sis (AHS). Previous data demonstrate an increase of hori- zontally oriented neurons in molecular layers of hip- pocampal subfields, which are immunoreactive for calre- tinin (CR-ir) and resemble Cajal-Retzius-like cells. Cajal- Retzius cells are transiently expressed in the murine de- veloping hippocampus and are critically involved in neu- ronal pattern formation. Here we investigated a potential relationship between the distribution of horizontally ori- ented calretinin-immunoreactive neurons and the clinical history of TLE patients with AHS. Horizontally oriented neurons in the molecular layer of the hippocampal forma- tion have been visualized by antibodies against the cal- cium-binding proteins calretinin and calbindin D-28k. Cell counts derived from 27 epilepsy patients with AHS were compared with autopsy specimens from developing and adult normal human hippocampus (n = 26). During on- togeny, CR-ir cells showed a marked perinatal peak in the CA1 and dentate gyrus molecular layer (CA1-ML, DG-ML) followed by a gradual postnatal decline. In hip- pocampal specimens from TLE patients with AHS and seizure onset before the age of 4 years, significantly higher levels of CR-ir neurons in CA1-ML (P = 0.05) and DG-ML (P < 0.05) were encountered than in AHS patients without precipitating seizures or with an uneventful early medical history. However, all three groups had higher lev- els of CR-ir neurons compared to adult controls obtained at autopsy (P < 0.01). In addition, AHS specimens showed increased CR-ir neuropil staining throughout the DG-ML compared with the restricted distribution of CR-ir fibers within the superficial granule cell layer visible in controls. These findings suggest that a condsiderable number of TLE patients with AHS display signs of impaired hip- pocampal maturation and circuitry formation as indicated by increased numbers of Cajal-Retzius like cells. It re- mains to be elucidated, how these changes contribute to the pathogenesis of TLE.