We induced limbic (SE) in rats by microinfusing pmolar doses of cyclothiazide+bicuculline into the anterior extent of the piriform cortex (APC), which is the brain site with the lowest threshold to seizures. This approach allows to evaluate selectively the effects of seizure spreading through the natural anatomical circuitries, differently from SE induced by systemic administration of kainate or pilocarpine. Acutely, we assessed seizure behavior, EEG and seizure spreading [(by c-Fos and F-desoxyglucose (FDG) uptake]. Chronically, we assessed hippocampal mossy fiber sprouting, and the occurrence of neuronal loss, degenerative phenomena (by Fluoro-Jade B-FJB- staining) and expression of heat shock protein-70 (HSP-70) in the hippocampus, piriform cortex and ventromedial thalamus. We further analyzed in detail SE chronic effects in basal forebrain cholinergic areas, the medial septal nucleus (MSN), the diagonal band of Broca (DBB) and the Nucleus basalis of Meynert (NBM), as these nuclei are strictly connected with limbic structures, and play a key role in cognitive functions and vigilance. We showed that during SE, epileptic activity spread to brain regions downstream to APC as shown by seizure features, EEG, c-Fos and FDG. Chronically, SE induces effects resembling human hippocampal sclerosis, together with cell loss and degeneration in limbic cortical and thalamic areas. Finally, we showed a significant cell loss, FJB-staining and HSP-70 expression within MSN, DBB and NBM ipsi- and contra-laterally to the infusion site. We provide direct evidence of SE-induced neuronal damage which is solely due to seizure activity. The damage in basal forebrain cholinergic nuclei might be particularly relevant in terms of chronic cognitive effects of limbic SE.

LOSS OF FOREBRAIN CHOLINERGIC NEURONS PURELY INDUCED BY SEIZURE SPREADING IN FOCALLY INDUCED LIMBIC STATUS EPILEPTICUS

Giorgi FS;Fornai F
2018-01-01

Abstract

We induced limbic (SE) in rats by microinfusing pmolar doses of cyclothiazide+bicuculline into the anterior extent of the piriform cortex (APC), which is the brain site with the lowest threshold to seizures. This approach allows to evaluate selectively the effects of seizure spreading through the natural anatomical circuitries, differently from SE induced by systemic administration of kainate or pilocarpine. Acutely, we assessed seizure behavior, EEG and seizure spreading [(by c-Fos and F-desoxyglucose (FDG) uptake]. Chronically, we assessed hippocampal mossy fiber sprouting, and the occurrence of neuronal loss, degenerative phenomena (by Fluoro-Jade B-FJB- staining) and expression of heat shock protein-70 (HSP-70) in the hippocampus, piriform cortex and ventromedial thalamus. We further analyzed in detail SE chronic effects in basal forebrain cholinergic areas, the medial septal nucleus (MSN), the diagonal band of Broca (DBB) and the Nucleus basalis of Meynert (NBM), as these nuclei are strictly connected with limbic structures, and play a key role in cognitive functions and vigilance. We showed that during SE, epileptic activity spread to brain regions downstream to APC as shown by seizure features, EEG, c-Fos and FDG. Chronically, SE induces effects resembling human hippocampal sclerosis, together with cell loss and degeneration in limbic cortical and thalamic areas. Finally, we showed a significant cell loss, FJB-staining and HSP-70 expression within MSN, DBB and NBM ipsi- and contra-laterally to the infusion site. We provide direct evidence of SE-induced neuronal damage which is solely due to seizure activity. The damage in basal forebrain cholinergic nuclei might be particularly relevant in terms of chronic cognitive effects of limbic SE.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/940413
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