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Vascular endothelial growth factor‐C modulates cortical NMDA receptor activity in cortical lesions of young patients and rat model with focal cortical dysplasia
Emergence of dysmorphic neurons is the primary pathology in focal cortical dysplasia (FCD) associated pediatric intractable epilepsy; however, the etiologies related to the development and function of dysmorphic neurons are not fully understood. Our previous studies revealed that the expression of v...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9425019/ https://www.ncbi.nlm.nih.gov/pubmed/35259773 http://dx.doi.org/10.1111/bpa.13065 |
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author | Shen, Kai‐Feng Duan, Qing‐Tian Duan, Wei Xu, Sen‐Lin An, Ning Ke, Yan‐Yan Wang, Li‐Ting Liu, Shi‐Yong Yang, Hui Zhang, Chun‐Qing |
author_facet | Shen, Kai‐Feng Duan, Qing‐Tian Duan, Wei Xu, Sen‐Lin An, Ning Ke, Yan‐Yan Wang, Li‐Ting Liu, Shi‐Yong Yang, Hui Zhang, Chun‐Qing |
author_sort | Shen, Kai‐Feng |
collection | PubMed |
description | Emergence of dysmorphic neurons is the primary pathology in focal cortical dysplasia (FCD) associated pediatric intractable epilepsy; however, the etiologies related to the development and function of dysmorphic neurons are not fully understood. Our previous studies revealed that the expression of vascular endothelial growth factor‐C (VEGF‐C) and corresponding receptors VEGFR‐2, VEGFR‐3 was increased in the epileptic lesions of patients with tuberous sclerosis complex or mesial temporal lobe epilepsy. Here, we showed that the expression of VEGF‐C, VEGFR‐2, and VEGFR‐3 was increased at both mRNA and protein levels in patients with cortical lesions of type I, IIa, and IIb FCD. The immunoreactivity of VEGF‐C, VEGFR‐2 and VEGFR‐3 was located in the micro‐columnar neurons in FCD type I lesions, dysplastic neurons (DNs) in FCD type IIa lesions, balloon cells (BCs) and astrocytes in FCD type IIb lesions. Additionally, the amplitude of evoked‐EPSCs (eEPSC) mediated by NMDA receptor, the ratio of NMDA receptor‐ and AMPA receptor‐mediated eEPSC were increased in the dysmorphic neurons of FCD rats established by prenatal X‐ray radiation. Furthermore, NMDA receptor mediated current in dysmorphic neurons was further potentiated by exogenous administration of VEGF‐C, however, could be antagonized by ki8751, the blocker of VEGFR‐2. These results suggest that VEGF‐C system participate in the pathogenesis of cortical lesions in patients with FCD in association with modulating NMDA receptor–mediated currents. |
format | Online Article Text |
id | pubmed-9425019 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94250192022-08-31 Vascular endothelial growth factor‐C modulates cortical NMDA receptor activity in cortical lesions of young patients and rat model with focal cortical dysplasia Shen, Kai‐Feng Duan, Qing‐Tian Duan, Wei Xu, Sen‐Lin An, Ning Ke, Yan‐Yan Wang, Li‐Ting Liu, Shi‐Yong Yang, Hui Zhang, Chun‐Qing Brain Pathol Research Articles Emergence of dysmorphic neurons is the primary pathology in focal cortical dysplasia (FCD) associated pediatric intractable epilepsy; however, the etiologies related to the development and function of dysmorphic neurons are not fully understood. Our previous studies revealed that the expression of vascular endothelial growth factor‐C (VEGF‐C) and corresponding receptors VEGFR‐2, VEGFR‐3 was increased in the epileptic lesions of patients with tuberous sclerosis complex or mesial temporal lobe epilepsy. Here, we showed that the expression of VEGF‐C, VEGFR‐2, and VEGFR‐3 was increased at both mRNA and protein levels in patients with cortical lesions of type I, IIa, and IIb FCD. The immunoreactivity of VEGF‐C, VEGFR‐2 and VEGFR‐3 was located in the micro‐columnar neurons in FCD type I lesions, dysplastic neurons (DNs) in FCD type IIa lesions, balloon cells (BCs) and astrocytes in FCD type IIb lesions. Additionally, the amplitude of evoked‐EPSCs (eEPSC) mediated by NMDA receptor, the ratio of NMDA receptor‐ and AMPA receptor‐mediated eEPSC were increased in the dysmorphic neurons of FCD rats established by prenatal X‐ray radiation. Furthermore, NMDA receptor mediated current in dysmorphic neurons was further potentiated by exogenous administration of VEGF‐C, however, could be antagonized by ki8751, the blocker of VEGFR‐2. These results suggest that VEGF‐C system participate in the pathogenesis of cortical lesions in patients with FCD in association with modulating NMDA receptor–mediated currents. John Wiley and Sons Inc. 2022-03-08 /pmc/articles/PMC9425019/ /pubmed/35259773 http://dx.doi.org/10.1111/bpa.13065 Text en © 2022 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Research Articles Shen, Kai‐Feng Duan, Qing‐Tian Duan, Wei Xu, Sen‐Lin An, Ning Ke, Yan‐Yan Wang, Li‐Ting Liu, Shi‐Yong Yang, Hui Zhang, Chun‐Qing Vascular endothelial growth factor‐C modulates cortical NMDA receptor activity in cortical lesions of young patients and rat model with focal cortical dysplasia |
title | Vascular endothelial growth factor‐C modulates cortical NMDA receptor activity in cortical lesions of young patients and rat model with focal cortical dysplasia |
title_full | Vascular endothelial growth factor‐C modulates cortical NMDA receptor activity in cortical lesions of young patients and rat model with focal cortical dysplasia |
title_fullStr | Vascular endothelial growth factor‐C modulates cortical NMDA receptor activity in cortical lesions of young patients and rat model with focal cortical dysplasia |
title_full_unstemmed | Vascular endothelial growth factor‐C modulates cortical NMDA receptor activity in cortical lesions of young patients and rat model with focal cortical dysplasia |
title_short | Vascular endothelial growth factor‐C modulates cortical NMDA receptor activity in cortical lesions of young patients and rat model with focal cortical dysplasia |
title_sort | vascular endothelial growth factor‐c modulates cortical nmda receptor activity in cortical lesions of young patients and rat model with focal cortical dysplasia |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9425019/ https://www.ncbi.nlm.nih.gov/pubmed/35259773 http://dx.doi.org/10.1111/bpa.13065 |
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