Increased protein expression of VEGF-A, VEGF-B, VEGF-C and their receptors in the temporal neocortex of pharmacoresistant temporal lobe epilepsy patients

Castañeda‐Cabral, José Luis; Beas‐Zárate, Carlos; Rocha-Arrieta, Luisa L.; Orozco‐Suárez, Sandra; Alonso-Vanegas, Mario; Guevara‐Guzmán, Rosalinda; Ureña‐Guerrero, Mónica E.

doi:10.1016/j.jneuroim.2018.12.007

Cited by 27 publications

(23 citation statements)

References 30 publications

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“…VEGF-C and VEGFR-3 are upregulated in various diseases, including myocardial infarction, experimental autoimmune encephalomyelitis, ischemic stroke, and epilepsy [192021222324254142]. Consistent with previous results, our immunohistochemistry results showed increased VEGF-C and VEGFR-3 expressing cells in the hippocampus after acute seizures.…”

Section: Discussionsupporting

confidence: 92%

“…Interestingly, several papers reported increased expression of VEGF-C and VEGFR-3 in the brains of patients with epilepsy [232425]. Moreover, when all three VEGF receptors were inhibited by sunitinib after acute seizures, spontaneous recurrent seizures were not observed compared to controls who generated recurrent seizures within one week post-pilocarpine [26].…”

Section: Introductionmentioning

confidence: 99%

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Increased expression of vascular endothelial growth factor-C and vascular endothelial growth factor receptor-3 after pilocarpine-induced status epilepticus in mice

Cho

Kim

Jeong

et al. 2019

Korean J Physiol Pharmacol

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Vascular endothelial growth factor (VEGF)-C and its receptor, vascular endothelial growth factor receptor (VEGFR)-3, are responsible for lymphangiogenesis in both embryos and adults. In epilepsy, the expression of VEGF-C and VEGFR-3 was significantly upregulated in the human brains affected with temporal lobe epilepsy. Moreover, pharmacologic inhibition of VEGF receptors after acute seizures could suppress the generation of spontaneous recurrent seizures, suggesting a critical role of VEGF-related signaling in epilepsy. Therefore, in the present study, the spatiotemporal expression of VEGF-C and VEGFR-3 against pilocarpine-induced status epilepticus (SE) was investigated in C57BL/6N mice using immunohistochemistry. At 1 day after SE, hippocampal astrocytes and microglia were activated. Pyramidal neuronal death was observed at 4 days after SE. In the subpyramidal zone, VEGF-C expression gradually increased and peaked at 7 days after SE, while VEGFR-3 was significantly upregulated at 4 days after SE and began to decrease at 7 days after SE. Most VEGF-C/VEGFR-3-expressing cells were pyramidal neurons, but VEGF-C was also observed in some astrocytes in sham-manipulated animals. However, at 4 days and 7 days after SE, both VEGFR-3 and VEGF-C immunoreactivities were observed mainly in astrocytes and in some microglia of the stratum radiatum and lacunosum-moleculare of the hippocampus, respectively. These data indicate that VEGF-C and VEGFR-3 can be upregulated in hippocampal astrocytes and microglia after pilocarpine-induced SE, providing basic information about VEGF-C and VEGFR-3 expression patterns following acute seizures.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Increased expression of vascular endothelial growth factor-C and vascular endothelial growth factor receptor-3 after pilocarpine-induced status epilepticus in mice

Cho

Kim

Jeong

et al. 2019

Korean J Physiol Pharmacol

View full text Add to dashboard Cite

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“…Additionally, BBB leakage could induce excessive angiogenesis and increase blood flow. These abnormalities are possibly induced by vascular endothelial growth factor (VEGF), whose expression is reported to be increased in the brains of patients with TLE (Rigau et al, 2007;Castañeda-Cabral et al, 2019). VEGF, which is produced and secreted from several types of cells, such as fibrocytes, myocytes, and astrocytes, under pathological conditions (de Vries et al, 1992), modulates the function of several types of cells, especially endothelial cells (Lee et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Vascular Abnormalities and the Role of Vascular Endothelial Growth Factor in the Epileptic Brain

2020

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Epilepsy is a chronic neurological disorder generally defined to be caused by excessive neuronal activity. Thus, excessive neuronal activity is the main target of the currently used antiepileptic drugs (AEDs). However, as many as 30% of epileptic patients show drug resistance to currently available AEDs, which suggests that epilepsy should be attributed not only to neuronal cells but also to other brain cells, such as glial cells and vascular cells. Astrocytes, pericytes, and endothelial cells in particular comprise the blood-brain barrier (BBB), which tightly regulates the exchange of substances between the brain parenchyma and the circulating blood. It has been proposed that BBB dysfunction, especially barrier leakage, exacerbates epileptic progression, and conversely, that epileptic seizures induce barrier leakage. Furthermore, several studies have shown that BBB dysfunction is one of the main causes of drug resistance in epilepsy. To better understand the mechanisms that link BBB dysfunction and intractable epilepsy to gain insights for the future development of treatments, we review and discuss the relationships between epilepsy and brain vascular abnormalities, mainly by focusing on vascular malformation, BBB dysfunction, and excessive angiogenesis. Because these abnormalities have been reported to be caused by vascular endothelial growth factor (VEGF) in the ischemic brain, we discuss the possible role of VEGF in vascular abnormalities in the epileptic brain, in which the upregulation of VEGF levels has been reported. Both glial cells and endothelial cells express VEGF receptors (VEGFRs); thus, these cells are likely affected by increases in VEGF during seizures, which in turn could cause vascular abnormalities. In this review, we review the possible role of VEGF in epilepsy and discuss the mechanisms that link vascular abnormalities and intractable epilepsy.

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“…PLCγ also activated PCK by producing diglycerides and promoting calcium aggregation in the cells. In addition, Akt phosphorylation activated endothelial nitric oxide(eNO) to regulate the production of nitric oxide and vascular permeability (Castaneda‐Cabral et al, ).…”

Section: Discussionmentioning

confidence: 99%

Heparin/poly‐l‐lysine nanoplatform with growth factor delivery for surface modification of cardiovascular stents: The influence of vascular endothelial growth factor loading

Tan

Cui

Zeng

et al. 2020

J Biomedical Materials Res

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The rapid re‐endothelialization of the vascular stent surface is desirable for preventing thrombosis or reducing restenosis. Many biological factors that promote the biological behavior of endothelial cells have been used for the surface modification of stents. Vascular endothelial growth factor (VEGF), which plays an important role in angiogenesis, induces strong vascular growth. In this study, we investigated different VEGF concentrations (50 to 500 ng/ml) to determine the optimum concentration for biocompatibility. First, VEGF‐loaded heparin/poly‐l‐lysine (Hep‐PLL) nanoparticles were created by electrostatic interactions. Then, the VEGF‐loaded nanoparticles were immobilized on dopamine‐coated 316 L stainless steel (SS) surfaces. The physical and chemical properties of the modified surface were characterized and the biocompatibility was evaluated in vitro. The results indicated that the VEGF‐loaded nanoparticles were immobilized successfully on the 316LSS surface, as evidenced by the results of Alcian Blue staining and water contact angle (WCA) measurements. The low platelet adhesion and activation indicated that the modified surfaces had good blood compatibility. The modified surfaces showed a good inhibitory effect on smooth muscle cells, indicating that they inhibited tissue hyperplasia. In addition, the modified surfaces significantly promoted endothelial cell adhesion, proliferation, migration, and biological activity, especially VEGF concentration was 350 ng/ml (NPV350). The optical VEGF concentration of the surface modified Hep‐PLL nanoparticles was 350 ng/ml. The proposed method shows promise for potential applications for cardiovascular devices.

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Increased protein expression of VEGF-A, VEGF-B, VEGF-C and their receptors in the temporal neocortex of pharmacoresistant temporal lobe epilepsy patients

Cited by 27 publications

References 30 publications

Increased expression of vascular endothelial growth factor-C and vascular endothelial growth factor receptor-3 after pilocarpine-induced status epilepticus in mice

Increased expression of vascular endothelial growth factor-C and vascular endothelial growth factor receptor-3 after pilocarpine-induced status epilepticus in mice

Vascular Abnormalities and the Role of Vascular Endothelial Growth Factor in the Epileptic Brain

Heparin/poly‐l‐lysine nanoplatform with growth factor delivery for surface modification of cardiovascular stents: The influence of vascular endothelial growth factor loading

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