Cellular pathology of hilar neurons in Ammon's horn sclerosis

Abstract

In addition to functionally affected neuronal signaling pathways, altered axonal, dendritic, and synaptic morphology may contribute to hippocampal hyperexcitability in chronic mesial temporal lobe epilepsies (MTLE). The sclerotic hippocampus in Ammon's horn sclerosis (AHS)‐associated MTLE, which shows segmental neuronal cell loss, axonal reorganization, and astrogliosis, would appear particularly susceptible to such changes. To characterize the cellular hippocampal pathology in MTLE, we have analyzed hilar neurons in surgical hippocampus specimens from patients with MTLE. Anatomically well‐preserved hippocampal specimens from patients with AHS (n = 44) and from patients with focal temporal lesions (non‐AHS; n = 20) were studied using confocal laser scanning microscopy (CFLSM) and electron microscopy (EM). Hippocampal samples from three tumor patients without chronic epilepsies and autopsy samples were used as controls. Using intracellular Lucifer Yellow injection and CFLSM, spiny pyramidal, multipolar, and mossy cells as well as non‐spiny multipolar neurons have been identified as major hilar cell types in controls and lesion‐associated MTLE specimens. In contrast, none of the hilar neurons from AHS specimens displayed a morphology reminiscent of mossy cells. In AHS, a major portion of the pyramidal and multipolar neurons showed extensive dendritic ramification and periodic nodular swellings of dendritic shafts. EM analysis confirmed the altered cellular morphology, with an accumulation of cytoskeletal filaments and increased numbers of mitochondria as the most prominent findings. To characterize cytoskeletal alterations in hilar neurons further, immunohistochemical reactions for neurofilament proteins (NFP), microtubule‐associated proteins, and tau were performed. This analysis specifically identified large and atypical hilar neurons with an accumulation of low weight NFP. Our data demonstrate striking structural alterations in hilar neurons of patients with AHS compared with controls and non‐sclerotic MTLE specimens. Such changes may develop during cellular reorganization in the epileptogenic hippocampus and are likely to contribute to the pathogenesis or maintenance of temporal lobe epilepsy. J. Comp. Neurol. 414:437–453, 1999. © 1999 Wiley‐Liss, Inc.

Stabilizing dendritic structure as a novel therapeutic approach for epilepsy

“…Similar findings of spine loss and dendritic swelling have also been documented in pyramidal neurons of neocortex, including sites distant from the primary epileptogenic focus [57]. Other less common dendritic abnormalities that have been described in both neocortical and hippocampal epilepsy include changes in dendritic length, shape, and branching patterns, as well as a focal increase in dendritic spines [55][56][57][58][59].…”

“…Such pathological specimens obtained from or near the region of the epileptic focus in neocortex or hippocampus have revealed a number of abnormalities in dendrites, but most commonly demonstrate a loss of dendritic spines [50,51]. Dendritic spine loss is commonly seen in hippocampal pyramidal neurons and dentate granule cells in patients with temporal lobe epilepsy and may occur in isolation or associated with varicose swelling of the dendritic branches [52][53][54][55][56]. Similar findings of spine loss and dendritic swelling have also been documented in pyramidal neurons of neocortex, including sites distant from the primary epileptogenic focus [57].…”

HUPO Brain Proteome Project: Summary of the pilot phase and introduction of a comprehensive data reprocessing strategy

“…A standardised neuropathological evaluation of the hippocampus revealed Ammon's horn sclerosis (AHS), i.e. segmental neuronal cell loss in CA1 as well as CA3/4, gliosis, and axonal reorganisation [12]. The temporal lobe specimen showed heterotopic neurons in the white matter.…”

The Correlation between Genotype and Phenotype of Alzheimer's Disease

“…From then on, there were several studies that reported on the presence of senile plaques in patients with epilepsy [129]. Along with amyloid deposition, the other neuropathologic signature of dementia, tau, has also been reported in human epilepsy patients and in animal models of epilepsy [130]. Besides, atrophy of the mesial and lateral temporal regions on MRI and hypometabolism in the basal temporal region demonstrated by positron emission tomography studies were characteristic finding in both conditions [131,132].…”