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, (i) it is unclear if damage limitation or repair may prevent epileptogenesis; (ii) it is also uncertain which neurotrophic factor should be administered for limiting or repairing damage while avoiding possible pro-epileptic 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 considering the hurdles that will have to be overcome before clinical application.