Hippocampal FGF-2 and BDNF overexpression attenuates epileptogenesis-associated neuroinflammation and reduces spontaneous recurrent seizures

被引:108
作者
Bovolenta, Roberta [1 ]
Zucchini, Silvia [1 ]
Paradiso, Beatrice [1 ]
Rodi, Donata [1 ]
Merigo, Flavia [2 ]
Mora, Graciela Navarro [2 ,6 ,7 ]
Osculati, Francesco [2 ,4 ]
Berto, Elena [3 ]
Marconi, Peggy [3 ]
Marzola, Andrea [5 ]
Fabene, Paolo F. [2 ]
Simonato, Michele [1 ]
机构
[1] Univ Ferrara, Pharmacol Sect, Dept Clin & Expt Med, I-44100 Ferrara, Italy
[2] Univ Verona, Sect Anat, Dept Neurol Neuropsychol Morphol & Movement Sci, I-37100 Verona, Italy
[3] Univ Ferrara, Microbiol Sect, Dept Expt & Diagnost Med, I-44100 Ferrara, Italy
[4] IRCSS Bonino Pulejo, Messina, Italy
[5] Univ Ferrara, Sect Pathol, Dept Expt & Diagnost Med, I-44100 Ferrara, Italy
[6] CSIC, Inst Neurociencias, Alicante, Spain
[7] Univ Miguel Hernandez, Alacant, Spain
来源
JOURNAL OF NEUROINFLAMMATION | 2010年 / 7卷
关键词
TEMPORAL-LOBE EPILEPSY; BRAIN-BARRIER DISRUPTION; NEUROTROPHIC FACTOR; STATUS EPILEPTICUS; INFLAMMATORY CYTOKINES; VASCULAR CHANGES; MODEL; CHEMOKINES; RECEPTOR; ASTROCYTES;
D O I
10.1186/1742-2094-7-81
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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-1 beta expression. The effect appeared to be most prominent on IL-1 beta, 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-1 beta in particular. Nonetheless, the concept that neurotrophic factors affect neuroinflammation in vivo may be highly relevant for the understanding of the epileptogenic process.
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页数:6
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