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Degeneration of cholinergic basal forebrain nuclei after focally evoked status epilepticus.
Biagioni, Francesca; Gaglione, Anderson; Giorgi, Filippo S; Bucci, Domenico; Moyanova, Slavianka; De Fusco, Antonio; Madonna, Michele; Fornai, Francesco.
Affiliation
  • Biagioni F; I.R.C.C.S. I.N.M. Neuromed, via dell'Elettronica 4, 86077, Pozzilli, Italy.
  • Gaglione A; I.R.C.C.S. I.N.M. Neuromed, via dell'Elettronica 4, 86077, Pozzilli, Italy.
  • Giorgi FS; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, via Roma 55, Pisa 56126, Italy; Section of Neurology, Department of Clinical and Experimental Medicine, Pisa University Hospital, University of Pisa, via Roma 67, Pisa 56126, Italy.
  • Bucci D; I.R.C.C.S. I.N.M. Neuromed, via dell'Elettronica 4, 86077, Pozzilli, Italy.
  • Moyanova S; I.R.C.C.S. I.N.M. Neuromed, via dell'Elettronica 4, 86077, Pozzilli, Italy.
  • De Fusco A; I.R.C.C.S. I.N.M. Neuromed, via dell'Elettronica 4, 86077, Pozzilli, Italy.
  • Madonna M; I.R.C.C.S. I.N.M. Neuromed, via dell'Elettronica 4, 86077, Pozzilli, Italy.
  • Fornai F; I.R.C.C.S. I.N.M. Neuromed, via dell'Elettronica 4, 86077, Pozzilli, Italy; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, via Roma 55, Pisa 56126, Italy. Electronic address: francesco.fornai@med.unipi.it.
Neurobiol Dis ; 121: 76-94, 2019 01.
Article de En | MEDLINE | ID: mdl-30243733
ABSTRACT
Status epilepticus (SE) of limbic onset might cause degenerative phenomena in different brain structures, and may be associated with chronic cognitive and EEG effects. In the present study SE was evoked focally by microinfusing picomolar doses of cyclothiazide+bicuculline into the anterior extent of the piriform cortex (APC) in rats, the so-called area tempestas, an approach which allows to evaluate selectively the effects of seizure spreading through the natural anatomical circuitries up to secondary generalization. In the brain of rats submitted to SE we analyzed neuronal density, occurrence of degenerative phenomena (by Fluoro-Jade B-FJB- staining) and expression of heat shock protein-70 (HSP-70) in the piriform cortex, the hippocampus and ventromedial thalamus. We further analyzed in detail, the loss of cholinergic neurons, and the presence of FJB- and HSP-70 positive neurons in basal forebrain cholinergic areas, i.e. the medial septal nucleus (MSN, Ch1), the diagonal band of Broca (DBB, Ch2 and Ch3) and the Nucleus basalis of Meynert (NBM, Ch4). In fact, these nuclei are strictly connected with limbic structures, and play a key pivotal role in different cognitive functions and vigilance. Although recent studies begun to investigate these nuclei in experimental epilepsy and in persons with epilepsy, conflicting results were obtained so far. We showed that after severe and long-lasting, focally induced limbic SE there is a significant cell loss within all of the abovementioned cholinergic nuclei ipsi- and contra-laterally to the infusion site. In parallel, these nuclei show also FJB and heat shock protein-70 expression. Those effects vary depending on the single nucleus assessed and on the severity of the SE seizure score. We also showed the occurrence of cell loss and degenerative phenomena in limbic cortex, hippocampus and limbic thalamic areas. These novel findings show direct evidence of SE-induced neuronal damage which is solely due to seizure activity ruling out potential confounding effects produced by systemic pro-convulsant neurotoxins. A damage to basal forebrain cholinergic nuclei, which may underlie cognitive alterations, is documented for the first time in a model of SE triggered focally.
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Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: État de mal épileptique / Encéphale / Neurones cholinergiques / Prosencéphale basal Type d'étude: Prognostic_studies Limites: Animals Langue: En Journal: Neurobiol Dis Sujet du journal: NEUROLOGIA Année: 2019 Type de document: Article Pays d'affiliation: Italie

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: État de mal épileptique / Encéphale / Neurones cholinergiques / Prosencéphale basal Type d'étude: Prognostic_studies Limites: Animals Langue: En Journal: Neurobiol Dis Sujet du journal: NEUROLOGIA Année: 2019 Type de document: Article Pays d'affiliation: Italie
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