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Angiogenesis is associated with blood-brain barrier permeability in temporal lobe epilepsy
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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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“BBB dysfunction positively correlates with seizure frequency and is independent of neuronal loss (234, 499).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [499]
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“Increased microvascular density, loss of tight junctions, and IgG leakage are observed in hippocampal resections from humans with temporal lobe epilepsy (499), and are also observed in rodent epileptic models (145, 499).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [499]
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Abbasova, K., Zybina, A., Куличенкова, К. Н., & Solodkov, R. (2016) · Human Physiology · doi:10.1134/s0362119716050029
Haeren (2018) · doi:10.26481/dis.20181026rh
Wadayama, T., Ito, A., Otsubo, R., Otani, K., Morikawa, M., & Ueda, N. (2019) · Rinsho Shinkeigaku · doi:10.5692/clinicalneurol.cn-001289
Cheng, Q. (2019) · Biomedical Journal of Scientific & Technical Research · doi:10.26717/bjstr.2019.18.003184
Yevtushenko, S. K., Sukhonosova, O. Y., Omel'ianenko, A. A., & Voronova, A. V. (2014) · INTERNATIONAL NEUROLOGICAL JOURNAL · doi:10.22141/2224-0713.7.69.2014.80900
Blood-brain barrier disruption in a model of neonatal hypoxic-ischaemic encephalopathy
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Metadata
- 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)
- 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
- 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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