Angiogenesis is associated with blood-brain barrier permeability in temporal lobe epilepsy

被引:326
|
作者
Rigau, Valerie
Morin, Melanie
Rousset, Marie-Claude
de Bock, Frederic
Lebrun, Aurore
Coubes, Philippe
Picot, Marie-Christine
Baldy-Moulinier, Michel
Bockaert, Joel
Crespel, Arielle
Lerner-Natoli, Mireille
机构
[1] Univ Montpellier I, Ctr Natl Rech Sci, UMR 5203, F-34094 Montpellier, France
[2] Univ Montpellier 2, Ctr Natl Rech Sci, UMR 5203, F-34094 Montpellier, France
[3] Inst Sante Rech Med, U6661, F-34295 Montpellier, France
[4] CHU Montpellier, Lab Anat & Cytol Pathol, F-34295 Montpellier, France
[5] CHU Montpellier, Unite Epileptol, F-34295 Montpellier, France
关键词
temporal lobe epilepsy; angiogenesis; vascular endothelial growth factor; blood-brain barrier disruption; IgG leakage;
D O I
10.1093/brain/awm118
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Previous studies from our group, focusing on neuro-glial remodelling in human temporal lobe epilepsy (TLE), have shown the presence of immature vascular cells in various areas of the hippocampus. Here, we investigated angiogenic processes in hippocampi surgically removed from adult patients suffering from chronic intractable TLE, with various aetiologies. We compared hippocampi from TLE patients to hippocampi obtained after surgery or autopsy from non-epileptic patients (NE). We quantified the vascular density, checked for the expression of angiogenic factors and their receptors and looked for any blood-brain barrier (BBB) leakage. We used a relevant model of rat limbic epilepsy, induced by lithium-pilocarpine treatment, to understand the sequence of events. In humans, the vessel density was significantly higher inTLE than in NE patients. This was neither dependent on the aetiology nor on the degree of neuronal loss, but was positively correlated with seizure frequency. In the whole hippocampus, we observed many complex, tortuous microvessels. In the dentate gyrus, when the granular layer was dispersed, long microvessels appeared radially orientated. Vascular endothelial factor (VEGF) and tyrosine kinase receptors were detected in different types of cells. An impairment of the BIBB was demonstrated by the loss of tight junctions and by Immunoglobulines G (IgG) leakage and accumulation in neurons. In the rat model of TLE,VEGF over-expression and BBB impairment occurred early after status epilepticus, followed by a progressive increase in vascularization. In humans and rodents, angiogenic processes and BBB disruption were still obvious in the chronic focus, probably activated by recurrent seizures. We suggest that the persistent leakage of serum IgG in the interstitial space and their uptake by neurons may participate in hypoperfusion and in neuronal dysfunction occurring inTLE.
引用
收藏
页码:1942 / 1956
页数:15
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