Stereological methods reveal the robust size and stability of ectopic hilar granule cells after pilocarpine‐induced status epilepticus in the adult rat

Abstract

Following status epilepticus in the rat, dentate granule cell neurogenesis increases greatly, and many of the new neurons appear to develop ectopically, in the hilar region of the hippocampal formation. It has been suggested that the ectopic hilar granule cells could contribute to the spontaneous seizures that ultimately develop after status epilepticus. However, the population has never been quantified, so it is unclear whether it is substantial enough to have a strong influence on epileptogenesis. To quantify this population, the total number of ectopic hilar granule cells was estimated using unbiased stereology at different times after pilocarpine-induced status epilepticus. The number of hilar neurons immunoreactive for Prox-1, a granule-cell-specific marker, was estimated using the optical fractionator method. The results indicate that the size of the hilar ectopic granule cell population after status epilepticus is substantial, and stable over time. Interestingly, the size of the population appears to be correlated with the frequency of behavioral seizures, because animals with more ectopic granule cells in the hilus have more frequent behavioral seizures. The hilar ectopic granule cell population does not appear to vary systematically across the septotemporal axis, although it is associated with an increase in volume of the hilus. The results provide new insight into the potential role of ectopic hilar granule cells in the pilocarpine model of temporal lobe epilepsy.

Localized delivery of fibroblast growth factor–2 and brain-derived neurotrophic factor reduces spontaneous seizures in an epilepsy model

“…2Bb). These observations are consistent with the aberrant aspects of SE-induced neurogenesis (19,24). A slightly increased number of DCX-positive cells was also observed in the pyramidal gyrus (CA3 and CA1).…”

The Developmental Stage of Dentate Granule Cells Dictates Their Contribution to Seizure-Induced Plasticity

“…Furthermore, dendrites present on ectopic cells were excluded, as they were already located in the hilus. Others have demonstrated that aberrantly developing adult-born neurons stably integrate into the dentate circuitry (Scharfman et al, 2000;McCloskey et al, 2006) and that altered neurogenesis after SE is long lasting, with ectopic cells forming for many months after seizure induction (Rao et al, 2006;Jessberger et al, 2007). Thus, the extent of SE-induced neurogenesis abnormalities is likely even more severe than is suggested by our RV labeling.…”

Stereological analysis of GluR2-immunoreactive hilar neurons in the pilocarpine model of temporal lobe epilepsy: Correlation of cell loss with mossy fiber sprouting

“…Recently, McCloskey et al (2006) reported stereological data that indicated about an order of magnitude higher number of hilar ectopic granule cells (HEGCs) in normal rats than the number of granule cell-like GluR2-immunoreactive hilar neurons we found. These authors quantitated HEGCs based on their expression of the nuclear protein PROX-1.…”

“…Many hilar neurons degenerate and are replaced, in part, by ectopic granule cells (Parent et al, 1997;Scharfman et al, 2000;McCloskey et al, 2006). In addition, some granule cells in epileptic rat brain are found to have a basal dendrite, a process found less frequently in normal brain (Spigelman et al, 1998;Buckmaster and Dudek, 1999;Ribak et al, 2000).…”