Vascular endothelial growth factor is up-regulated after status epilepticus and protects against seizure-induced neuronal loss in hippocampus

Neuroscience. 2008 Jan 2;151(1):232-41. doi: 10.1016/j.neuroscience.2007.09.083. Epub 2007 Oct 26.


Vascular endothelial growth factor (VEGF) is a protein factor which has been found to play a significant role in both normal and pathological states. Its role as an angiogenic factor is well-established. More recently, VEGF has been shown to protect neurons from cell death both in vivo and in vitro. While VEGF's potential as a protective factor has been demonstrated in hypoxia-ischemia, in vitro excitotoxicity, and motor neuron degeneration, its role in seizure-induced cell loss has received little attention. A potential role in seizures is suggested by Newton et al.'s [Newton SS, Collier EF, Hunsberger J, Adams D, Terwilliger R, Selvanayagam E, Duman RS (2003) Gene profile of electroconvulsive seizures: Induction of neurotrophic and angiogenic factors. J Neurosci 23:10841-10851] finding that VEGF mRNA increases in areas of the brain that are susceptible to cell loss after electroconvulsive-shock induced seizures. Because a linear relationship does not always exist between expression of mRNA and protein, we investigated whether VEGF protein expression increased after pilocarpine-induced status epilepticus. In addition, we administered exogenous VEGF in one experiment and blocked endogenous VEGF in another to determine whether VEGF exerts a neuroprotective effect against status epilepticus-induced cell loss in one vulnerable brain region, the rat hippocampus. Our data revealed that VEGF is dramatically up-regulated in neurons and glia in hippocampus, thalamus, amygdala, and neocortex 24 h after status epilepticus. VEGF induced significant preservation of hippocampal neurons, suggesting that VEGF may play a neuroprotective role following status epilepticus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Vessels / drug effects
  • Blood Vessels / ultrastructure
  • Cell Death / physiology
  • Convulsants
  • Enzyme-Linked Immunosorbent Assay
  • Hippocampus / cytology
  • Hippocampus / metabolism*
  • Hippocampus / pathology*
  • Immunohistochemistry
  • In Vitro Techniques
  • Infusion Pumps, Implantable
  • Male
  • Neurons / metabolism*
  • Neurons / pathology*
  • Neuroprotective Agents
  • Pilocarpine
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Seizures / chemically induced
  • Seizures / metabolism*
  • Seizures / pathology*
  • Status Epilepticus / chemically induced
  • Status Epilepticus / metabolism*
  • Status Epilepticus / pathology*
  • Up-Regulation / drug effects
  • Vascular Endothelial Growth Factor A / biosynthesis*
  • Vascular Endothelial Growth Factor A / pharmacology
  • Vascular Endothelial Growth Factor A / physiology*


  • Convulsants
  • Neuroprotective Agents
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Pilocarpine