Locus coeruleus and neuronal plasticity in a model of focal limbic epilepsy

Filippo S. Giorgi, Giuseppe Mauceli, Fabio Blandini, Stefano Ruggieri, Antonio Paparelli, Luigi Murri, Francesco Fornai

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Purpose: A lesion of the noradrenergic nucleus Locus Coeruleus (LC) converts sporadic seizures evoked by microinfusion of bicuculline into the anterior piriform cortex (APC) of rats into limbic status epilepticus (SE). The purpose of this study was to evaluate the chronic effects of this new model of SE on the onset of secondary epileptogenesis. We further related the loss of noradrenaline (NE) with hippocampal mossy fiber sprouting. Methods: Male Sprague Dawley rats were treated with systemic saline or DSP-4 (a neurotoxin selective for noradrenergic terminals originating from the LC), microinfused with bicuculline into the APC three days later, and sacrificed after 45 days. Naïve and DSP-4 pretreated sham-operated rats served as respective controls. The following evaluations were performed: (a) monitoring of acute seizures and delayed occurrence of spontaneous recurrent seizures (SRS); (b) NE levels in the hippocampus, frontal and olfactory cortex; (c) occurrence of mossy fiber sprouting into the inner molecular layer of the dentate gyrus of the dorsal hippocampus. Results: In 30% of rats lacking noradrenergic terminals, SE evoked from the APC was followed by SRS. Conversely, seizures evoked in intact rats did not result in chronic epileptogenesis. Seizures/SE did not modify NE levels as compared with baseline levels both in naïve and DSP-4-pretreated rats. Rats undergoing SE following DSP-4 + bicuculline developed SRS which were accompanied by hippocampal mossy fiber sprouting. Conclusions: Noradrenergic loss converts focally induced sporadic seizures into an epileptogenic SE, which is accompanied by mossy fiber sprouting within the dentate gyrus.

Original languageEnglish
Pages (from-to)21-25
Number of pages5
JournalEpilepsia
Volume47
Issue numberSUPPL. 5
DOIs
Publication statusPublished - Dec 2006

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Neuronal Plasticity
Locus Coeruleus
Partial Epilepsy
Status Epilepticus
Seizures
Bicuculline
Hippocampal Mossy Fibers
Norepinephrine
Dentate Gyrus
Parahippocampal Gyrus
Neurotoxins
Frontal Lobe
Sprague Dawley Rats
Hippocampus
DSP 4

Keywords

  • DSP-4
  • Epileptogenesis
  • Mossy fiber sprouting
  • Noradrenaline
  • Piriform cortex
  • Status epilepticus

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Locus coeruleus and neuronal plasticity in a model of focal limbic epilepsy. / Giorgi, Filippo S.; Mauceli, Giuseppe; Blandini, Fabio; Ruggieri, Stefano; Paparelli, Antonio; Murri, Luigi; Fornai, Francesco.

In: Epilepsia, Vol. 47, No. SUPPL. 5, 12.2006, p. 21-25.

Research output: Contribution to journalArticle

Giorgi, FS, Mauceli, G, Blandini, F, Ruggieri, S, Paparelli, A, Murri, L & Fornai, F 2006, 'Locus coeruleus and neuronal plasticity in a model of focal limbic epilepsy', Epilepsia, vol. 47, no. SUPPL. 5, pp. 21-25. https://doi.org/10.1111/j.1528-1167.2006.00872.x
Giorgi, Filippo S. ; Mauceli, Giuseppe ; Blandini, Fabio ; Ruggieri, Stefano ; Paparelli, Antonio ; Murri, Luigi ; Fornai, Francesco. / Locus coeruleus and neuronal plasticity in a model of focal limbic epilepsy. In: Epilepsia. 2006 ; Vol. 47, No. SUPPL. 5. pp. 21-25.
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abstract = "Purpose: A lesion of the noradrenergic nucleus Locus Coeruleus (LC) converts sporadic seizures evoked by microinfusion of bicuculline into the anterior piriform cortex (APC) of rats into limbic status epilepticus (SE). The purpose of this study was to evaluate the chronic effects of this new model of SE on the onset of secondary epileptogenesis. We further related the loss of noradrenaline (NE) with hippocampal mossy fiber sprouting. Methods: Male Sprague Dawley rats were treated with systemic saline or DSP-4 (a neurotoxin selective for noradrenergic terminals originating from the LC), microinfused with bicuculline into the APC three days later, and sacrificed after 45 days. Na{\"i}ve and DSP-4 pretreated sham-operated rats served as respective controls. The following evaluations were performed: (a) monitoring of acute seizures and delayed occurrence of spontaneous recurrent seizures (SRS); (b) NE levels in the hippocampus, frontal and olfactory cortex; (c) occurrence of mossy fiber sprouting into the inner molecular layer of the dentate gyrus of the dorsal hippocampus. Results: In 30{\%} of rats lacking noradrenergic terminals, SE evoked from the APC was followed by SRS. Conversely, seizures evoked in intact rats did not result in chronic epileptogenesis. Seizures/SE did not modify NE levels as compared with baseline levels both in na{\"i}ve and DSP-4-pretreated rats. Rats undergoing SE following DSP-4 + bicuculline developed SRS which were accompanied by hippocampal mossy fiber sprouting. Conclusions: Noradrenergic loss converts focally induced sporadic seizures into an epileptogenic SE, which is accompanied by mossy fiber sprouting within the dentate gyrus.",
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AU - Mauceli, Giuseppe

AU - Blandini, Fabio

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AU - Paparelli, Antonio

AU - Murri, Luigi

AU - Fornai, Francesco

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KW - DSP-4

KW - Epileptogenesis

KW - Mossy fiber sprouting

KW - Noradrenaline

KW - Piriform cortex

KW - Status epilepticus

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