Proepileptic influence of a focal vascular lesion affecting entorhinal cortex-CA3 connections after status epilepticus

Giuseppe Biagini, Enrica Baldelli, Daniela Longo, Miranda Baccarani Contri, Uliano Guerrini, Luigi Sironi, Paolo Gelosa, Isabella Zini, David S. Ragsdale, Massimo Avoli

Research output: Contribution to journalArticle

Abstract

In limbic seizures, neuronal excitation is conveyed from the entorhinal cortex directly to CA1 and subicular regions. This phenomenon is associated with a reduced ability of CA3 to respond to entorhinal cortex inputs. Here, we describe a lesion that destroys the perforant path in CA3 after status epilepticus (SE) induced by pilocarpine injection in 8-week-old rats. Using magnetic resonance imaging, immunohistochemical, and ultrastructural analyses, we determined that this lesion develops after 30 minutes of SE and is characterized by microhemorrhages and ischemia. After a longer period of SE, the lesion invariably involves the upper blade of the dentate gyrus. Adult rats treated with subcutaneous diazepam (20 mg kg -1 for 3 days) did not develop the dentate gyrus lesion and had less frequent spontaneous recurrent seizures (p <0.01). Young (3-week-old) rats rarely (20%) developed the CA3 lesion, and their spontaneous seizures were delayed (p <0.01). To investigate the role of the damaged CA3 in seizure activity, we reinduced SE in adult and young epileptic rats. Using FosB/ΔFosB markers, we found induction of FosB/ΔFosB immunopositivity in CA3 neurons of young but not in adult rats. These experiments indicate that SE can produce a focal lesion in the perforant path that may affect the roles of the hippocampus in epileptic rats.

Original languageEnglish
Pages (from-to)687-701
Number of pages15
JournalJournal of Neuropathology and Experimental Neurology
Volume67
Issue number7
DOIs
Publication statusPublished - Jul 2008

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Keywords

  • Hemorrhage
  • Hippocampus
  • Immediate early genes
  • Ischemia
  • Magnetic resonance imaging
  • Pilocarpine
  • Temporal lobe epilepsy

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Neurology
  • Cellular and Molecular Neuroscience
  • Neuroscience(all)

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