title: Hippocampal FGF-2 and BDNF overexpression attenuates epileptogenesis-associated neuroinflammation and reduces spontaneous recurrent seizures.
abstract: Under certain experimental conditions, neurotrophic factors may reduce epileptogenesis. We have previously reported that local, intrahippocampal supplementation of fibroblast growth factor-2 (FGF-2) and brain-derived neurotrophic factor (BDNF) increases neurogenesis, reduces neuronal loss, and reduces the occurrence of spontaneous seizures in a model of damage-associated epilepsy. Here, we asked if these possibly anti-epileptogenic effects might involve anti-inflammatory mechanisms. Thus, we used a Herpes-based vector to supplement FGF-2 and BDNF in rat hippocampus after pilocarpine-induced status epilepticus that established an epileptogenic lesion. This model causes intense neuroinflammation, especially in the phase that precedes the occurrence of spontaneous seizures. The supplementation of FGF-2 and BDNF attenuated various parameters of inflammation, including astrocytosis, microcytosis and IL-1β expression. The effect appeared to be most prominent on IL-1β, whose expression was almost completely prevented. Further studies will be needed to elucidate the molecular mechanism(s) for these effects, and for that on IL-1β in particular. Nonetheless, the concept that neurotrophic factors affect neuroinflammation in vivo may be highly relevant for the understanding of the epileptogenic process.
authors.affiliation: Section of Pharmacology, Department of Clinical and Experimental Medicine, and Neuroscience Center, University of Ferrara, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Bovolenta
authors.forename: Silvia
authors.initials: S
authors.lastname: Zucchini
authors.forename: Beatrice
authors.initials: B
authors.lastname: Paradiso
authors.forename: Donata
authors.initials: D
authors.lastname: Rodi
authors.forename: Flavia
authors.initials: F
authors.lastname: Merigo
authors.forename: Graciela
authors.initials: G
authors.lastname: Navarro Mora
authors.forename: Francesco
authors.initials: F
authors.lastname: Osculati
authors.forename: Elena
authors.initials: E
authors.lastname: Berto
authors.forename: Peggy
authors.initials: P
authors.lastname: Marconi
authors.forename: Andrea
authors.initials: A
authors.lastname: Marzola
authors.forename: Paolo F
authors.initials: PF
authors.lastname: Fabene
authors.forename: Michele
authors.initials: M
authors.lastname: Simonato
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D004569:Electroencephalography; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007249:Inflammation / Q000473:pathology*; D053583:Interleukin-1beta / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D012008:Recurrence; D012640:Seizures / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control*; D013226:Status Epilepticus / Q000139:chemically induced / Q000473:pathology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D053583:Interleukin-1beta; D016222:Fibroblast Growth Factor 2