Age-dependent vascular changes induced by status epilepticus in rat forebrain: Implications for epileptogenesis

被引:76
作者
Marcon, Jessica [1 ]
Gagliardi, Barbara [1 ]
Balosso, Silvia [1 ]
Maroso, Mattia [1 ]
Noe, Francesco [1 ]
Morin, Melanie [2 ]
Lerner-Natoli, Mireille [2 ]
Vezzani, Annamaria [1 ]
Ravizza, Teresa [1 ]
机构
[1] Mario Negri Inst Pharmacol Res, Dept Neurosci, Lab Expt Neurol, I-20156 Milan, Italy
[2] Univ Montpellier 1, Inst Funct Genom, CNRS, INSERM,UMR 5203,U661, Montpellier, France
关键词
Albumin; Angiogenesis; BBB; Inflammation; IL-1; beta; Status epilepticus; BLOOD-BRAIN-BARRIER; TEMPORAL-LOBE EPILEPSY; ENDOTHELIAL GROWTH-FACTOR; IN-VITRO; NEURONAL INJURY; CORTICAL DEVELOPMENT; SPONTANEOUS SEIZURES; PILOCARPINE MODEL; GLUTAMATE UPTAKE; NITRIC-OXIDE;
D O I
10.1016/j.nbd.2008.12.018
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Brain inflammation, angiogenesis and increased blood-brain barrier (BBB) permeability occur in adult rodent and human epileptogenic brain tissue. We addressed the role of these events in epileptogenesis using a developmental approach since the propensity to develop spontaneous seizures, therefore the induction of epileptogenesis, is age-dependent and increases with brain maturation. Inflammation, angiogenesis; and BBB permeability were studied in postnatal day (PN)9 and PN21 rats, I week and 4 months after pilocarpine-induced status epilepticus. Brain inflammation was evaluated by interleukin(IL)-1 beta immunohistochemistry; angiogenesis was quantified by measuring the density of microvessels; identified by an and-laminin antibody or by the intraluminal signal of FITC-albumin; BBB integrity was assessed by extravascular IgG immunostaining or detection of parenchymal extravasation of FITC-albumin. Neither inflammation nor angiogenesis or changes in BBB permeability were detected in PN9 rats after status epilepticus, and these rats did not develop spontaneous seizures in adulthood as assessed by video-EEG monitoring. Differently, status epilepticus in PN21 rats induced chronic inflammation, angiogenesis and BBB leakage in the hippocampus in 62% of rats, while in the remaining rats only transient inflammation in forebrain was observed. Epilepsy developed in about 62% of PN21 rats exposed to SE and these epileptic rats showed the three phenomena concomitantly in the hippocampus. PN21 rats that did not develop epilepsy 4 months after status epilepticus, as assessed by video-EEG monitoring, they did not show inflammation, angiogenesis or BBB damage in forebrain at this time. Our data show that age-dependent vascular changes and brain inflammation induced by status epilepticus are associated with epileptogenesis, suggesting that these phenomena are implicated in the mechanisms underlying the occurrence of spontaneous seizures. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:121 / 132
页数:12
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