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Original Article

Korean J Physiol Pharmacol 2019; 23(4): 281-289

Published online July 1, 2019 https://doi.org/10.4196/kjpp.2019.23.4.281

Copyright © The Korean Journal of Physiology & Pharmacology.

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

Kyung-Ok Cho1,2,3,4,#, Joo Youn Kim1,#, Kyoung Hoon Jeong1, Mun-Yong Lee2,3,5, and Seong Yun Kim1,2,3,*

1Department of Pharmacology, College of Medicine, The Catholic University of Korea, 2Department of Biomedicine & Health Sciences, The Catholic University of Korea, 3Catholic Neuroscience Institute, 4Institute of Aging and Metabolic Diseases, 5Department of Anatomy, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea

Correspondence to:Seong Yun Kim
E-mail: syk@catholic.ac.kr

Received: April 14, 2019; Revised: May 7, 2019; Accepted: May 8, 2019

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.

Keywords: Hippocampus, Mouse, Vascular endothelial growth factor-C, Vascular endothelial growth factor, receptor-3, Status epilepticus