Increased expression of vascular endothelial growth factor-C and vascular endothelial growth factor receptor-3 after pilocarpine-induced status epilepticus in mice
10.4196/kjpp.2019.23.4.281
- Author:
Kyung Ok CHO
1
;
Joo Youn KIM
;
Kyoung Hoon JEONG
;
Mun Yong LEE
;
Seong Yun KIM
Author Information
1. Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. syk@catholic.ac.kr
- Publication Type:Original Article
- Keywords:
Hippocampus;
Mouse;
Vascular endothelial growth factor-C;
Vascular endothelial growth factor receptor-3;
Status epilepticus
- MeSH:
Adult;
Animals;
Astrocytes;
Brain;
Embryonic Structures;
Epilepsy;
Epilepsy, Temporal Lobe;
Hippocampus;
Humans;
Immunohistochemistry;
Lymphangiogenesis;
Mice;
Microglia;
Pyramidal Cells;
Receptors, Vascular Endothelial Growth Factor;
Seizures;
Status Epilepticus;
Vascular Endothelial Growth Factor A;
Vascular Endothelial Growth Factor C;
Vascular Endothelial Growth Factor Receptor-3
- From:The Korean Journal of Physiology and Pharmacology
2019;23(4):281-289
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
