Vascular endothelial growth factor is up-regulated after status epilepticus and protects against seizure-induced neuronal loss in hippocampus.
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.
City University of New York, New York, NY 10016, USA.
J N
JN
Nicoletti
S K
SK
Shah
D P
DP
McCloskey
J H
JH
Goodman
A
A
Elkady
H
H
Atassi
D
D
Hylton
J S
JS
Rudge
H E
HE
Scharfman
S D
SD
Croll
D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000648:ultrastructure; D016923:Cell Death / Q000502:physiology; D003292:Convulsants; D004797:Enzyme-Linked Immunosorbent Assay; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism* / Q000473:pathology*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D015918:Infusion Pumps, Implantable; D008297:Male; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D018696:Neuroprotective Agents; D010862:Pilocarpine; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D015854:Up-Regulation / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000494:pharmacology / Q000502:physiology*
D003292:Convulsants; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D010862:Pilocarpine