Are the neurotrophic factors a suitable therapeutic target for the prevention of epileptogenesis?
Neurotrophic factors are involved in the survival of neurons as well as in the proliferation and differentiation of neuronal precursors. Therefore, modulating their levels in lesion areas may exert favorable effects on seizure-induced damage. However, it is unclear if damage limitation or repair may prevent epileptogenesis; it is also uncertain which neurotrophic factor should be administered for limiting or repairing damage while avoiding possible proepileptic effects. We used viral vectors to locally supplement fibroblast growth factor-2 (FGF-2) and brain-derived neurotrophic factor (BDNF), when an epileptogenic damage was already in place. These vectors were tested in the pilocarpine model of status epilepticus-induced neurodegeneration and epileptogenesis. FGF-2/BDNF expressing vectors increased neuronogenesis, limited neuronal damage, and reduced the occurrence of spontaneous seizures. These findings are discussed with consideration of the hurdles that will have to be overcome before clinical application.
Simonato
Michele
M
Section of Pharmacology, Department of Clinical and Experimental Medicine, Neuroscience Center, University of Ferrara, and National Institute of Neuroscience, Ferrara, Italy. michele.simonato@unife.it
Zucchini
Silvia
S
D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology / Q000627:therapeutic use; D004834:Epilepsy, Post-Traumatic / Q000188:drug therapy* / Q000517:prevention & control / Q000628:therapy; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology / Q000627:therapeutic use; D015316:Genetic Therapy; D005822:Genetic Vectors; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D009414:Nerve Growth Factors / Q000494:pharmacology / Q000627:therapeutic use*
D000927:Anticonvulsants; D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D016222:Fibroblast Growth Factor 2