PMID- 19366663 OWN - NLM STAT- MEDLINE DCOM- 20090605 LR - 20211020 IS - 1091-6490 (Electronic) IS - 0027-8424 (Print) IS - 0027-8424 (Linking) VI - 106 IP - 17 DP - 2009 Apr 28 TI - Localized delivery of fibroblast growth factor-2 and brain-derived neurotrophic factor reduces spontaneous seizures in an epilepsy model. PG - 7191-6 LID - 10.1073/pnas.0810710106 [doi] AB - A loss of neurons is observed in the hippocampus of many patients with epilepsies of temporal lobe origin. It has been hypothesized that damage limitation or repair, for example using neurotrophic factors (NTFs), may prevent the transformation of a normal tissue into epileptic (epileptogenesis). Here, we used viral vectors to locally supplement two NTFs, fibroblast growth factor-2 (FGF-2) and brain-derived neurotrophic factor (BDNF), when epileptogenic damage was already in place. These vectors were first characterized in vitro, where they increased proliferation of neural progenitors and favored their differentiation into neurons, and they were then tested in a model of status epilepticus-induced neurodegeneration and epileptogenesis. When injected in a lesioned hippocampus, FGF-2/BDNF expressing vectors increased neuronogenesis, embanked neuronal damage, and reduced epileptogenesis. It is concluded that reduction of damage reduces epileptogenesis and that supplementing specific NTFs in lesion areas represents a new approach to the therapy of neuronal damage and of its consequences. FAU - Paradiso, Beatrice AU - Paradiso B AD - Department of Clinical and Experimental Medicine, Section of Pharmacology, University of Ferrara, 44100 Ferrara, Italy. FAU - Marconi, Peggy AU - Marconi P FAU - Zucchini, Silvia AU - Zucchini S FAU - Berto, Elena AU - Berto E FAU - Binaschi, Anna AU - Binaschi A FAU - Bozac, Aleksandra AU - Bozac A FAU - Buzzi, Andrea AU - Buzzi A FAU - Mazzuferi, Manuela AU - Mazzuferi M FAU - Magri, Eros AU - Magri E FAU - Navarro Mora, Graciela AU - Navarro Mora G FAU - Rodi, Donata AU - Rodi D FAU - Su, Tao AU - Su T FAU - Volpi, Ilaria AU - Volpi I FAU - Zanetti, Lara AU - Zanetti L FAU - Marzola, Andrea AU - Marzola A FAU - Manservigi, Roberto AU - Manservigi R FAU - Fabene, Paolo F AU - Fabene PF FAU - Simonato, Michele AU - Simonato M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090406 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 103107-01-3 (Fibroblast Growth Factor 2) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Cell Proliferation MH - Epilepsy/*genetics/metabolism/pathology/*therapy MH - Fibroblast Growth Factor 2/genetics/*metabolism MH - Genetic Therapy MH - Genetic Vectors/genetics MH - Male MH - Neurogenesis MH - Rats MH - Rats, Sprague-Dawley MH - Seizures/*genetics/metabolism/pathology/*therapy MH - Treatment Outcome PMC - PMC2678472 COIS- The authors declare no conflict of interest. EDAT- 2009/04/16 09:00 MHDA- 2009/06/09 09:00 PMCR- 2009/10/28 CRDT- 2009/04/16 09:00 PHST- 2009/04/16 09:00 [entrez] PHST- 2009/04/16 09:00 [pubmed] PHST- 2009/06/09 09:00 [medline] PHST- 2009/10/28 00:00 [pmc-release] AID - 0810710106 [pii] AID - 7574 [pii] AID - 10.1073/pnas.0810710106 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7191-6. doi: 10.1073/pnas.0810710106. Epub 2009 Apr 6.