Different patterns of neuronal activation and neurodegeneration in the thalamus and cortex of epilepsy‐resistant Proechimys rats versus Wistar rats after pilocarpine‐induced protracted seizures

Abstract

SUMMARYPurpose: To analyze cellular mechanisms of limbic-seizure suppression, the response to pilocarpine-induced seizures was investigated in cortex and thalamus, comparing epilepsy-resistant rats Proechimys guyannensis with Wistar rats. Methods: Fos immunoreactivity revealing neuronal activation, and degenerating neurons labeled by Fluoro-Jade B (FJB) histochemistry were analyzed on the first day after onset of seizures lasting 3 h. Subpopulations of c-aminobutyric acid (GABA)ergic cells were characterized with double Fos-parvalbumin immunohistochemistry. Results: In both cortex and thalamus, degenerating neurons were much fewer in Proechimys than Wistar rats. Fos persisted at high levels at 24 h only in the Proechimys thalamus and cortex, especially in layer VI where corticothalamic neurons reside. In the parietal cortex, about 50% of parvalbumin-containing interneurons at 8 h, and 10-20% at 24 h, were Fos-positive in Wistar rats, but in Proechimys, Fos was expressed in almost all parvalbumin-containing interneurons at 8 h and dropped at 24 h. Fos positivity in cingulate cortex interneurons was similar in both species. In the Wistar rat thalamus, Fos was induced in medial and midline nuclei up to 8 h, when <30% of reticular nucleus cells were Fos-positive, and then decreased, with no relationship with cell loss, evaluated in Nissl-stained sections. In Proechimys, almost all reticular nucleus neurons were Fos-positive at 24 h. Discussion: At variance with laboratory rats, pilocarpine-induced protracted seizures elicit in Proechimys limited neuronal death, and marked and long-lasting Fos induction in excitatory and inhibitory cortical and thalamic cell subsets. The findings implicate intrathalamic and intracortical regulation, and circuits linking thalamus and cortex in limbic seizure suppression leading to epilepsy resistance.

Differences in activation of ERK1/2 and p38 kinase in Jnk3 null mice following KA treatment

“…2d vs. b). We also evaluated the presence of c‐ fos , an inducible transcription factor of the immediate‐early genes family (Kovacs 2008) highly expressed in the hippocampus following KA treatment, and it has been used as a nuclear marker of neuronal activation following seizures (Andrioli et al. 2009; Lopez‐Martin et al.…”

Cellular injury and neuroinflammation in children with chronic intractable epilepsy

“…To determine the cell types showing DNA fragmentation, we performed triple immunofluorescent staining for neuron, microglia or astrocytes using TSA-amplification with ISEL. Adjacent sections were processed for Fluoro-Jade B histochemistry as previously described [23] to confirm the detection of degenerating neurons by ISEL staining.…”

Redistribution of astrocytic glutamine synthetase in the hippocampus of chronic epileptic rats

“…Loss of parvalbumin (PV) interneurons in the subiculum of human TLE patients (Andrioli et al, 2009) parallels the loss of PV interneurons in the hilus, pre-, parasubiculum, and entorhinal cortex in epileptic rats (van Vliet et al, 2004). Astroglia dysfunction, in terms of potassium buffering capacity, has been described in the CA1 region of human and rat epileptic hippocampus .…”