Status epilepticus-induced pathologic plasticity in a rat model of focal cortical dysplasia

Francesca Colciaghi, Adele Finardi, Angelisa Frasca, Silvia Balosso, Paola Nobili, Giovanni Carriero, Denise Locatelli, Annamaria Vezzani, Giorgio Battaglia

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

We have generated an experimental 'double-hit' model of chronic epilepsy to recapitulate the co-existence of abnormal cortical structure and frequently recurrent seizures as observed in human focal cortical dysplasia. We induced cortical malformations by exposing rats prenatally to methylazoxymethanol acetate and triggered status epilepticus and recurrent seizures in adult methylazoxymethanol acetate rats with pilocarpine. We studied the course of epilepsy and the long-term morphologic and molecular changes induced by the occurrence of status epilepticus and subsequent chronic epilepsy in the malformed methylazoxymethanol acetate exposed brain. Behavioural and electroencephalographic analyses showed that methylazoxymethanol acetate pilocarpine rats develop more severe epilepsy than naïve rats. Morphologic and molecular analyses demonstrated that status epilepticus and subsequent seizures, but not pilocarpine treatment per se, was capable of affecting both cortical architectural and N-methyl-d-aspartate receptor abnormalities induced by methylazoxymethanol acetate. In particular, cortical thickness was further decreased and N-methyl-d-aspartate regulatory subunits were recruited at the postsynaptic membrane. In addition, methylazoxymethanol acetate pilocarpine rats showed abnormally large cortical pyramidal neurons with neurofilament over-expression. These neurons bear similarities to the hypertrophic/dysmorphic pyramidal neurons observed in acquired human focal cortical dysplasia. These data show that status epilepticus sets in motion a pathological process capable of significantly changing the cellular and molecular features of pre-existing experimental cortical malformations. They suggest that seizure recurrence in human focal cortical dysplasia might be an additional factor in establishing a pathological circuitry that favours chronic neuronal hyperexcitability.

Original languageEnglish
Pages (from-to)2828-2843
Number of pages16
JournalBrain
Volume134
Issue number10
DOIs
Publication statusPublished - 2011

Fingerprint

Methylazoxymethanol Acetate
Malformations of Cortical Development
Status Epilepticus
Pilocarpine
Epilepsy
Seizures
Pyramidal Cells
Intermediate Filaments
Pathologic Processes
Aspartic Acid
Neurons
Recurrence
Membranes
Brain

Keywords

  • double-hit model
  • epilepsy
  • malformation of cortical development
  • NMDA receptor
  • seizures

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Colciaghi, F., Finardi, A., Frasca, A., Balosso, S., Nobili, P., Carriero, G., ... Battaglia, G. (2011). Status epilepticus-induced pathologic plasticity in a rat model of focal cortical dysplasia. Brain, 134(10), 2828-2843. https://doi.org/10.1093/brain/awr045

Status epilepticus-induced pathologic plasticity in a rat model of focal cortical dysplasia. / Colciaghi, Francesca; Finardi, Adele; Frasca, Angelisa; Balosso, Silvia; Nobili, Paola; Carriero, Giovanni; Locatelli, Denise; Vezzani, Annamaria; Battaglia, Giorgio.

In: Brain, Vol. 134, No. 10, 2011, p. 2828-2843.

Research output: Contribution to journalArticle

Colciaghi, F, Finardi, A, Frasca, A, Balosso, S, Nobili, P, Carriero, G, Locatelli, D, Vezzani, A & Battaglia, G 2011, 'Status epilepticus-induced pathologic plasticity in a rat model of focal cortical dysplasia', Brain, vol. 134, no. 10, pp. 2828-2843. https://doi.org/10.1093/brain/awr045
Colciaghi, Francesca ; Finardi, Adele ; Frasca, Angelisa ; Balosso, Silvia ; Nobili, Paola ; Carriero, Giovanni ; Locatelli, Denise ; Vezzani, Annamaria ; Battaglia, Giorgio. / Status epilepticus-induced pathologic plasticity in a rat model of focal cortical dysplasia. In: Brain. 2011 ; Vol. 134, No. 10. pp. 2828-2843.
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