Alterations in seizure susceptibility and in seizure-induced plasticity after pharmacologic and genetic manipulation of the fibroblast growth factor-2 system.
OBJECTIVE
The adult brain undergoes activity-dependent plastic modifications during pathologic processes that are reminiscent of those observed during development. For example, seizures induce neuronal loss, neurogenesis, axonal and dendritic sprouting, gliosis, and circuit remodeling. Neurotrophic factors and fibroblast growth factor-2 (FGF-2), in particular, are well-known mediators in each of these cellular events. The aim of this minireview is to summarize and discuss the data supporting the idea that FGF-2 may be involved in seizure generation and in their sequelae.


METHODS
We used epilepsy models of kainate and kindling, with FGF-2 knockout mice and FGF-2 overexpressing mice.


RESULTS
Seizures increase FGF-2 mRNA and protein levels in specific brain areas and upregulate the expression of its receptor FGFR-1. Short-term intrahippocampal injection of FGF-2 cause seizures, whereas long-term i.c.v. infusion of low-dose FGF-2 does not affect kainate seizures but promotes behavioral recovery and reduces hippocampal damage. Kainate seizure severity is not altered in FGF-2 knockout mice, but is increased in FGF-2 overexpressing mice.


CONCLUSIONS
FGF-2 is implicated in seizure susceptibility and in seizure-induced plasticity.
Department of Clinical and Experimental Medicine, Section of Pharmacology, and Neuroscience Center, University of Ferrara, Ferrara, Italy. silvia.zucchini@unife.it
Silvia
S
Zucchini
Mario
M
Barbieri
Michele
M
Simonato
D000818:Animals; D004195:Disease Models, Animal; D004827:Epilepsy / Q000503:physiopathology*; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D006801:Humans; D007696:Kindling, Neurologic / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000502:physiology*; D012640:Seizures / Q000503:physiopathology
D016222:Fibroblast Growth Factor 2