Loss of hilar mossy cells in Ammon's horn sclerosis

Purpose: Hilar mossy cells represent an important excitatory subpopulation of the hippocampal formation. Several studies have identified this cell typ e as particularly vulnerable to seizure activity in rat models of limbic ep ilepsy. Hen we have subjected hilar mossy cell loss in the hippocampus of p atients with chronic temporal lobe epilepsy (TLE) to a systematic morpholog ical and immunohistochemical analysis. Methods: Hippocampal specimens from 30 TLE patients were included; 21 patie nts presented with segmental neuronal cell loss [Ammon's horns clerosis (AH S)] and 8 with focal Lesions (tumors, scars, malformations) not involving t he hippocampus proper. In one additional TLE patient, no histopathological alteration could be observed. Surgical specimens from tumor patients withou t epilepsy (n = 2) and nonepileptic autopsy brains(n = 8) were used as cont rols. Hilar mossy cells in the human hippocampus were visualized using a no vel poly cloncal antiserum directed against the metabotropic glutamate rece ptor subtype mGluR7b or by intracellular Lucifer Yellow injection. confocal laser scanning microscopy, and three-dimensional morphological reconstruct ion. Results: Compared with controls, a significant loss of mGluR7 immunoreactiv e mossy cells was observed in patients with AHS (p < 0.05). In contrast, TL E patients with focal lesions but structurally intact hippocampus demonstra ted only a discrete, nonsignificant reduction of this neuronal subpopulatio n, This observation was confirmed by analysis of 62 randomly injected hilar neurons from AHS patients, in which we were unable to detect neurons with a morphology like that of hilar mossy cells. Conclusion: Our present data indicate significant hilar mossy cell loss in TLE patients with AHS. In contrast, hilar mossy cells appear to be less vul nerable in patients with lesion-associated TLE. Although the significance o f mGluR7 immunoreactivity in mossy cells remains to be studied, loss of thi s cell population is compatible with alterations in hippocampal networks an d regional hyperexcitability as pathogenic mechanism of AHS and TLE.