Elevated Expression of VEGF-C and Its Receptors, VEGFR-2 and VEGFR-3, in Patients with Mesial Temporal Lobe Epilepsy

J Mol Neurosci. 2016 Jun;59(2):241-50. doi: 10.1007/s12031-016-0714-y. Epub 2016 Jan 21.

Abstract

Mesial temporal lobe epilepsy (MTLE) is a frequent form of focal intractable epilepsy in adults. We previously reported overexpression of vascular endothelial growth factor C (VEGF-C) and its receptors, VEGFR-2 and VEGFR-3, in epilepsy-associated tuberous sclerosis complex. To identify whether VEGF-C and its receptors are involved in epileptogenesis of MTLE, we investigated the levels and expression pattern of VEGF-C and its receptors in temporal neocortex and hippocampus (HPC) from 28 patients with MTLE and ten control (CTX) subjects. Real-time quantitative polymerase chain reaction and Western blotting results revealed upregulated mRNA and immunoreactive protein levels of VEGF-C, VEGFR-2, and VEGFR-3 in the MTLE group compared to the control groups. Immunohistochemistry and double-labeled immunofluorescence showed that VEGF-C was highly expressed in neurons and astrocytes, including reactive astrocytes and vascular endothelial cells, VEGFR-2 was expressed at a high level in reactive astrocytes and vascular endothelial cells, but not in neurons, whereas VEGFR-3 was only overexpressed in reactive astrocytes. Taken together, these findings suggest that VEGF-C and its receptors, VEGFR-2 and VEGFR-3, may contribute to the epileptogenesis of MTLE.

Keywords: Hippocampus; Mesial temporal lobe epilepsy; Receptors; Temporal neocortex; Vascular endothelial growth factor C.

MeSH terms

  • Adolescent
  • Adult
  • Astrocytes / metabolism
  • Case-Control Studies
  • Epilepsy, Temporal Lobe / genetics
  • Epilepsy, Temporal Lobe / metabolism*
  • Female
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Humans
  • Male
  • Neocortex / cytology
  • Neocortex / metabolism
  • Neurons / metabolism
  • Vascular Endothelial Growth Factor C / genetics
  • Vascular Endothelial Growth Factor C / metabolism*
  • Vascular Endothelial Growth Factor Receptor-2 / genetics
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism*
  • Vascular Endothelial Growth Factor Receptor-3 / genetics
  • Vascular Endothelial Growth Factor Receptor-3 / metabolism*

Substances

  • Vascular Endothelial Growth Factor C
  • Vascular Endothelial Growth Factor Receptor-2
  • Vascular Endothelial Growth Factor Receptor-3