Cited by 429Barrier Structure and Function StudiesEpilepsy research and treatmentAngiogenesis and VEGF in Cancer

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

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Rigau, V., Morin, M., Rousset, M.-C., de Bock, F., Lebrun, A., Coubes, P., Picot, M.-C., Baldy-Moulinier, M., Bockaert, J., Crespel, A., Lerner-Natoli, M.·2007·Brain

DOI 10.1093/brain/awm118

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Abstract

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 in TLE 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 BBB 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 in TLE.

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Authors: Rigau, V., Morin, M., Rousset, M.-C., de Bock, F., Lebrun, A., Coubes, P., Picot, M.-C., Baldy-Moulinier, M., Bockaert, J., Crespel, A., & Lerner-Natoli, M.
Affiliations: Centre National de la Recherche Scientifique (FR)
ORCID: Rigau, V.
Coubes, P.
Picot, M.-C.
Bockaert, J.
Crespel, A.
Venue: Brain
Publisher: Oxford University Press (OUP)
Published: 2007-05-29
Volume: 130
Issue: 7
Pages: 1942-1956
ISSN: 0006-8950 (ISSN-L)
1460-2156
DOI: 10.1093/brain/awm118
OpenAlex: W2109644106
Cited by: 429
References: 53
Citations by year: 2026: 10 · 2025: 13 · 2024: 18 · 2023: 13 · 2022: 17 · 2021: 17 · 2020: 35 · 2019: 19 · 2018: 23 · 2017: 23 · 2016: 26 · 2015: 22 · 2014: 32 · 2013: 24 · 2012: 37
FWCI: 14.10
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Brain (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion, other-oa)
Topics: Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Health Sciences › Medicine › Clinical Neurology › Epilepsy research and treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Keywords: temporal lobe epilepsy, angiogenesis, blood-brain barrier permeability, hippocampus, vascular endothelial growth factor, receptor tyrosine kinase, tight junctions, vessel density, dentate gyrus, status epilepticus, lithium-pilocarpine model, limbic epilepsy, hypoperfusion, neuronal dysfunction, seizure frequency
MeSH terms: Adolescent, Adult, Animals, Blood-Brain Barrier, Brain, Child, Disease Models, Animal, Epilepsy, Temporal Lobe, Female, Hippocampus, Humans, Male, Middle Aged, Neovascularization, Pathologic, Neurons, Permeability, Cell Death, Rats, Sprague-Dawley, Vascular Endothelial Growth Factor Receptor-2, Vascular Endothelial Growth Factor A, Receptor, TIE-2, Angiogenesis Inducing Agents, Rats

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

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