title: Proepileptic influence of a focal vascular lesion affecting entorhinal cortex-CA3 connections after status epilepticus.
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 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/DeltaFosB markers, we found induction of FosB/DeltaFosB 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.
authors.affiliation: Dipartimento di Scienze Biomediche, Università di Modena e Reggio Emilia, Modena, Italy. gbiagini@unimore.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Biagini
authors.forename: Enrica
authors.initials: E
authors.lastname: Baldelli
authors.forename: Daniela
authors.initials: D
authors.lastname: Longo
authors.forename: Miranda Baccarani
authors.initials: MB
authors.lastname: Contri
authors.forename: Uliano
authors.initials: U
authors.lastname: Guerrini
authors.forename: Luigi
authors.initials: L
authors.lastname: Sironi
authors.forename: Paolo
authors.initials: P
authors.lastname: Gelosa
authors.forename: Isabella
authors.initials: I
authors.lastname: Zini
authors.forename: David S
authors.initials: DS
authors.lastname: Ragsdale
authors.forename: Massimo
authors.initials: M
authors.lastname: Avoli
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000627:therapeutic use; D001930:Brain Injuries / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy / Q000473:pathology*; D003975:Diazepam / Q000627:therapeutic use; D004195:Disease Models, Animal; D018728:Entorhinal Cortex / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D005786:Gene Expression Regulation / Q000187:drug effects; D020662:Guanine Nucleotide Exchange Factors; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D007797:Laminin / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009434:Neural Pathways / Q000473:pathology / Q000648:ultrastructure; D010862:Pilocarpine; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D064067:Rho Guanine Nucleotide Exchange Factors; D013226:Status Epilepticus / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy / Q000473:pathology* / Q000517:prevention & control
chemical_list: C577228:ARHGEF5 protein, human; D000927:Anticonvulsants; D020662:Guanine Nucleotide Exchange Factors; D007797:Laminin; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D064067:Rho Guanine Nucleotide Exchange Factors; D010862:Pilocarpine; D051547:Heme Oxygenase-1; D003975:Diazepam