title: Long-term neuronal replacement in adult rat hippocampus after status epilepticus despite chronic inflammation.
abstract: Dentate gyrus (DG) neurogenesis is transiently increased during the first weeks after status epilepticus (SE). Survival of the new neurons is initially compromised by an acute inflammatory response, but the long-term fate of the remaining ones in the post-SE environment is unknown. Here adult rats were subjected to 2 h electrically evoked self-sustained SE and perfused after 5 weeks or 6 months. Rats exhibited partial or generalized SE followed by spontaneous behavioural seizures and abnormal electroencephalographic activity during 6 months. Numbers of activated microglia in the dentate subgranular zone (SGZ)-granule cell layer (GCL) and in the hilus declined after 5 weeks, but were still elevated at 6 months after SE, with no differences between the milder partial and the more severe generalized SE. At 6 months, partial and generalized SE rats showed a seven-fold increase in the number of mature SGZ-GCL neurons formed during the first 2 weeks along with aberrant neurons in the hilus. Total numbers of mature neurons in SGZ-GCL were unaltered, indicating that SE-generated neurons replaced dead granule cells. Neuroblast formation had returned to normal levels in SGZ-GCL but generation of aberrant neurons in the hilus was still ongoing at 6 months. Our data indicate that long-term impairment of neurogenesis, as reported previously after kainic acid-induced SE, is not a general feature of chronic epilepsy. We have found that a substantial proportion of the mature granule cells at 6 months are generated during the first 2 weeks after SE and survive despite chronic inflammation, and that SE triggers continuous production of aberrant hilar neurons.
authors.affiliation: Laboratory of Neurogenesis and Cell Therapy, Section of Restorative Neurology, Wallenberg Neuroscience Center, University Hospital, SE-221 84, Lund, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Bonde
authors.forename: Christine T
authors.initials: CT
authors.lastname: Ekdahl
authors.forename: Olle
authors.initials: O
authors.lastname: Lindvall
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D004195:Disease Models, Animal; D053331:Ectodysplasins; D004558:Electric Stimulation / Q000009:adverse effects; D004569:Electroencephalography / Q000379:methods; D005452:Fluoresceins; D005786:Gene Expression Regulation / Q000502:physiology / Q000528:radiation effects; D006624:Hippocampus / Q000473:pathology* / Q000528:radiation effects; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008840:Microfilament Proteins; D017628:Microglia / Q000502:physiology / Q000528:radiation effects; D009474:Neurons / Q000473:pathology* / Q000528:radiation effects; D009930:Organic Chemicals; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000209:etiology / Q000473:pathology; D013226:Status Epilepticus / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology*; D013997:Time Factors; D048069:Tumor Necrosis Factors / Q000378:metabolism
chemical_list: C100745:Aif1 protein, rat; D002135:Calcium-Binding Proteins; D053331:Ectodysplasins; D005452:Fluoresceins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009930:Organic Chemicals; D048069:Tumor Necrosis Factors; C435731:fluoro jade; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine