Under certain experimental conditions, neurotrophic factors may reduce epileptogenesis. We have previously reported that local, intrahippocampal supplementation of fibroblast growth factor-2 (FGF-2) and brain-derived neurotrophic factor (BDNF) increases neurogenesis, reduces neuronal loss, and reduces the occurrence of spontaneous seizures in a model of damage-associated epilepsy. Here, we asked if these possibly anti-epileptogenic effects might involve anti-inflammatory mechanisms. Thus, we used a Herpes-based vector to supplement FGF-2 and BDNF in rat hippocampus after pilocarpine-induced status epilepticus that established an epileptogenic lesion. This model causes intense neuroinflammation, especially in the phase that precedes the occurrence of spontaneous seizures. The supplementation of FGF-2 and BDNF attenuated various parameters of inflammation, including astrocytosis, microcytosis and IL-1β expression. The effect appeared to be most prominent on IL-1β, whose expression was almost completely prevented. Further studies will be needed to elucidate the molecular mechanism(s) for these effects, and for that on IL-1β in particular. Nonetheless, the concept that neurotrophic factors affect neuroinflammation in vivo may be highly relevant for the understanding of the epileptogenic process.

SUMMARYPurpose: We have recently reported that viral vectormediated supplementation of fibroblast growth factor-2 (FGF-2) and brain-derived neurotrophic factor (BDNF) in a lesioned, epileptogenic rat hippocampus limits neuronal damage, favors neurogenesis, and reduces spontaneous recurrent seizures. To test if this treatment can also prevent hippocampal circuit reorganization, we examined here its effect on mossy fiber sprouting, the best studied form of axonal plasticity in epilepsy. Methods: A herpes-based vector expressing FGF-2 and BDNF was injected into the rat hippocampus 3 days after an epileptogenic insult (pilocarpine-induced status epilepticus). Continuous video-electroencephalography (EEG) monitoring was initiated 7 days after status epilepticus, and animals were sacrificed at 28 days for analysis of cell loss (measured using NeuN immunofluorescence) and mossy fiber sprouting (measured using dynorphin A immunohistochemistry). Key Findings: The vector expressing FGF-2 and BDNF decreased both mossy fiber sprouting and the frequency and severity of spontaneous seizures. The effect on sprouting correlated strictly with the cell loss in the terminal fields of physiologic mossy fiber innervation (mossy cells in the dentate gyrus hilus and CA3 pyramidal neurons). Significance: These data suggest that the supplementation of FGF-2 and BDNF in an epileptogenic hippocampus may prevent epileptogenesis by decreasing neuronal loss and mossy fiber sprouting, that is, reducing some forms of circuit reorganization.

The aim of this study was to evaluate polyurethane percutaneous endoscopic gastrostomy (PEG) tube degradation and the role played by fungi. The inner surfaces of 20 used polyurethane tubes were brushed, and the brushing end was incubated for 7 days in Saburaud broth and cultured if fungal growth occurred. Three tubes used for 12 (sample 12w), 17 (sample 17w), and 96 (sample 96w) weeks and two new tubes were cut to produce several 4-cm-long equal halves. Six samples from the new tubes were considered control samples (Co sample), seven were incubated in Saburaud broth (Co sample + Sa.), and seven in the broth supplemented with Candida albicans (Co sample + Sa. + Ca). All samples underwent morphological examination by electron microscopy and differential scanning calorimetry measurements (DSC). All tubes had fungal colonization. DSC showed deterioration in all tubes including the new ones; adding Candida albicans had no additional effects. Morphological examination by electron microscopy showed a regular pattern in the Co sample, and thick biofilm, holes, and crevices in samples 12w, 17w, and 96w. The more the tubes had been used, the more severe were the changes. The Co sample + Sa and the Co sample + Sa + Ca showed no changes in the inner surface, but cryogenically fractured surfaces had holes and crevices. Yeasts constantly colonize PEG tubes and are likely to contribute to polyurethane deterioration. The impairment of new PEG tubes incubated in Saburaud broth suggests that other factors also play a role in polyurethane deterioration.