Expression of VEGF- and tight junction-related proteins in the neocortical microvasculature of patients with drug-resistant temporal lobe epilepsy

被引:21
作者
Luis Castaneda-Cabral, Jose [1 ,2 ]
Colunga-Duran, Adacrid [1 ]
Urena-Guerrero, Monica E. [2 ]
Beas-Zarate, Carlos [2 ]
de los Angeles Nunez-Lumbreras, Maria [1 ]
Orozco-Suarez, Sandra [3 ]
Alonso-Vanegas, Mario [4 ,8 ]
Guevara-Guzman, Rosalinda [5 ]
Deli, Maria A. [6 ]
Guadalupe Valle-Dorado, Maria [1 ]
Sanchez-Valle, Vicente [7 ]
Rocha, Luisa [1 ]
机构
[1] Inst Politecn Nacl Cinvestav, Ctr Invest & Estudios Avanzados, Dept Farmacobiol, Sede Sur, Ciudad De Mexico, Mexico
[2] Univ Guadalajara, Ctr Univ Ciencias Biol & Agr CUCBA, Dept Biol Celular & Mol, Zapopan, Mexico
[3] Hosp Especialidades Ctr Med La Raza, Ctr Med Nacl Siglo XXI, Unidad Invest Med Enfermedades Neurol, IMSS, Ciudad De Mexico, Mexico
[4] Inst Nacl Neurol & Neurocirugia Manuel Velasco Su, Serv Neurocirugia, Ciudad De Mexico, Mexico
[5] Univ Nacl Autonoma Mexico, Fac Med, Dept Fisiol, Ciudad De Mexico, Mexico
[6] Hungarian Acad Sci, Biol Res Ctr, Inst Biophys, Szeged, Hungary
[7] CINVESTAV, Dept Farmacol, Ciudad De Mexico, Mexico
[8] Hosp HMG Coyoacan, Ctr Int Cirugia Epilepsia, Ciudad De Mexico, Mexico
关键词
Blood-brain barrier; Claudin-5; Occludin; Microvessels; Temporal lobe epilepsy; Tight junction; VEGF; VEGFR-2; Zonula occludens; BLOOD-BRAIN-BARRIER; STATUS-EPILEPTICUS; DISRUPTION; ANGIOGENESIS; PERMEABILITY; HIPPOCAMPUS; RECEPTORS; LEAKAGE;
D O I
10.1016/j.mvr.2020.104059
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
The blood-brain barrier (BBB) maintains the optimal microenvironment for brain function. Tight junctions (TJs) allow endothelial cells to adhere to each other, leading to the formation of a barrier that prevents the penetration of most molecules via transcellular routes. Evidence has indicated that seizure-induced vascular endothelial growth factor (VEGF) type 2 receptor (VEGFR-2) pathway activation weakens TJs, inducing vasodilatation and increasing vascular permeability and subsequent brain injury. The present study focused on investigating the expression levels of VEGF-related (VEGF-A and VEGFR-2) and TJ-related proteins (claudin-5, occludin and ZO-1) in the neocortical microvasculature of patients with drug-resistant temporal lobe epilepsy (TLE). The results obtained from hippocampal sclerosis TLE (HS-TLE) patients were compared with those obtained from patients with TLE secondary to lesions (lesion-TLE) and autopsy samples. The Western blotting and immunofluorescence results showed that VEGF-A and VEGFR-2 protein expression levels were increased in HS-TLE and lesion-TLE patients compared to autopsy group. On the other hand, claudin-5 expression was higher in HS-TLE patients and lesion-TLE patients than autopsies. The expression level of occludin and ZO-1 was decreased in HS-TLE patients. Our study described modifications to the integrity of the BBB that may contribute to the pathogenesis of TLE, in which the VEGF system may play an important role. We demonstrated that the same modifications were present in both HS-TLE and lesion-TLE patients, which suggests that seizures modify these systems and that they are not associated with the establishment of epilepsy.
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页数:9
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