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

• Published in: Neuroscience Vol. 151; no. 1; pp. 232 - 241
• Main Authors: Nicoletti, J.N, Shah, S.K, McCloskey, D.P, Goodman, J.H, Elkady, A, Atassi, H, Hylton, D, Rudge, J.S, Scharfman, H.E, Croll, S.D
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 02.01.2008
• Subjects: amygdala; 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; neocortex; Neurology; Neurons - metabolism; Neurons - pathology; neuroprotection; Neuroprotective Agents; neurotrophic; Pilocarpine; Rats; Rats, Sprague-Dawley; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Seizures - chemically induced; Seizures - metabolism; Seizures - pathology; Status Epilepticus - chemically induced; Status Epilepticus - metabolism; Status Epilepticus - pathology; thalamus; Up-Regulation - drug effects; Vascular Endothelial Growth Factor A - biosynthesis; Vascular Endothelial Growth Factor A - pharmacology; Vascular Endothelial Growth Factor A - physiology; amygdala; fetal liver kinase (receptor); human Fc domain of IgG; hFc; thickness sampling fraction; tsf; ssf; section sampling fraction; National Institutes of Health; phosphate-buffered saline; rat endothelial cell antigen; Flt; analysis of variance; ANOVA; CA; thalamus; neurotrophic; PBS; VEGF; neocortex; cornus ammonis; NIH; area sampling fraction; GFAP; pilocarpine; asf; neuroprotection; vascular endothelial growth factor; enzyme-linked immunosorbent assay; RECA; glial fibrillary acidic protein; ELISA
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2007.09.083

Abstract 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.