Localized delivery of fibroblast growth factor-2 and brain-derived neurotrophic factor reduces spontaneous seizures in an epilepsy model

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 106; no. 17; pp. 7191 - 7196
• Main Authors: Paradiso, Beatrice, Marconi, Peggy, Zucchini, Silvia, Berto, Elena, Binaschi, Anna, Bozac, Aleksandra, Buzzi, Andrea, Mazzuferi, Manuela, Magri, Eros, Mora, Graciela Navarro, Rodi, Donata, Su, Tao, Volpi, Ilaria, Zanetti, Lara, Marzola, Andrea, Manservigi, Roberto, Fabene, Paolo F, Simonato, Michele
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 28-04-2009; National Acad Sciences
• Subjects: Animals; Biological Sciences; Brain; Brain damage; Brain-Derived Neurotrophic Factor - genetics; Brain-Derived Neurotrophic Factor - metabolism; Cell Proliferation; Dentate gyrus; Epilepsy; Epilepsy - genetics; Epilepsy - metabolism; Epilepsy - pathology; Epilepsy - therapy; Fibroblast Growth Factor 2 - genetics; Fibroblast Growth Factor 2 - metabolism; Genetic Therapy; Genetic Vectors - genetics; Hippocampus; Inoculation; Male; Neurogenesis; Neurons; Progenitor cells; Rats; Rats, Sprague-Dawley; Seizures; Seizures - genetics; Seizures - metabolism; Seizures - pathology; Seizures - therapy; Stem cells; Tissues; Treatment Outcome
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0810710106

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.