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.
OBJECTIVE
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 gamma-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.


CONCLUSIONS
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.
Andrioli
Anna
A
Department of Morphological and Biomedical Sciences, Faculty of Medicine, University of Verona, Verona, Italy. anna@anatomy.univr.it
Fabene
Paolo F
PF
Spreafico
Roberto
R
Cavalheiro
Esper A
EA
Bentivoglio
Marina
M
D000704:Analysis of Variance; D000818:Animals; D002452:Cell Count / Q000379:methods; D002540:Cerebral Cortex / Q000473:pathology*; D004195:Disease Models, Animal; D004569:Electroencephalography; D004827:Epilepsy / Q000139:chemically induced / Q000150:complications* / Q000473:pathology*; D005452:Fluoresceins; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D009410:Nerve Degeneration / Q000209:etiology* / Q000378:metabolism; D009474:Neurons / Q000145:classification / Q000502:physiology*; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D009930:Organic Chemicals; D010320:Parvalbumins / Q000378:metabolism; D010862:Pilocarpine; D051381:Rats; D017208:Rats, Wistar; D013788:Thalamus / Q000473:pathology*; D013997:Time Factors
D005452:Fluoresceins; D016761:Oncogene Proteins v-fos; D009930:Organic Chemicals; D010320:Parvalbumins; C435731:fluoro jade; D010862:Pilocarpine