Localized delivery of fibroblast growth factor-2 and brain-derived neurotrophic factor reduces spontaneous seizures in an epilepsy model.
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.
Paradiso
Beatrice
B
Department of Clinical and Experimental Medicine, Section of Pharmacology, University of Ferrara, 44100 Ferrara, Italy.
Marconi
Peggy
P
Zucchini
Silvia
S
Berto
Elena
E
Binaschi
Anna
A
Bozac
Aleksandra
A
Buzzi
Andrea
A
Mazzuferi
Manuela
M
Magri
Eros
E
Navarro Mora
Graciela
G
Rodi
Donata
D
Su
Tao
T
Volpi
Ilaria
I
Zanetti
Lara
L
Marzola
Andrea
A
Manservigi
Roberto
R
Fabene
Paolo F
PF
Simonato
Michele
M
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D004827:Epilepsy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism*; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D008297:Male; D055495:Neurogenesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome
D019208:Brain-Derived Neurotrophic Factor; D016222:Fibroblast Growth Factor 2