title: VEGF, which is elevated in the CSF of patients with hydrocephalus, causes ventriculomegaly and ependymal changes in rats.
abstract: Hydrocephalus is a condition characterized primarily by excessive accumulation of fluid in the ventricles of the brain for which there is currently no effective pharmacological treatment. Surgery, often accompanied by complications, is the only current treatment. Extensive research in our laboratory along with work from others has suggested a link between hydrocephalus and vascular function. We hypothesized that vascular endothelial growth factor (VEGF), the major angiogenic factor, could play a role in the pathogenesis of hydrocephalus. We tested this hypothesis by examining two predictions of such a link: first, that VEGF is present in many cases of clinical hydrocephalus; and second, that exogenous VEGF in an animal model could cause ventricular enlargement and tissue changes associated with hydrocephalus. Our results support the idea that VEGF elevation can potentiate hydrocephalus. The clinical relevance of this work is that anti-angiogenic drugs may be useful in patients with hydrocephalus, either alone or in combination with the currently available surgical treatments.
authors.affiliation: Department of Neurosurgery, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA. simon.shim@gmail.com
authors.forename: Joon W
authors.initials: JW
authors.lastname: Shim
authors.forename: Johanna
authors.initials: J
authors.lastname: Sandlund
authors.forename: Carin H
authors.initials: CH
authors.lastname: Han
authors.forename: Mustafa Q
authors.initials: MQ
authors.lastname: Hameed
authors.forename: Susan
authors.initials: S
authors.lastname: Connors
authors.forename: Michael
authors.initials: M
authors.lastname: Klagsbrun
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Madsen
authors.forename: Nina
authors.initials: N
authors.lastname: Irwin
mesh_terms: D000293:Adolescent; D000328:Adult; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000068258:Bevacizumab; D015820:Cadherins / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004195:Disease Models, Animal; D004805:Ependyma / Q000187:drug effects*; D005260:Female; D006801:Humans; D006849:Hydrocephalus / Q000134:cerebrospinal fluid* / Q000139:chemically induced* / Q000188:drug therapy; D007223:Infant; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000134:cerebrospinal fluid* / Q000633:toxicity*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D055815:Young Adult; D051176:beta Catenin / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D015820:Cadherins; D042461:Vascular Endothelial Growth Factor A; D051176:beta Catenin; D000068258:Bevacizumab; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: 4′,6-diamidino-2-phenylindole; Bevacizumab; CSF; Cerebrospinal fluid; DAPI; Ependyma; Hydrocephalus; Permeability; VEGF; VEGFR2; Vascular endothelial growth factor; bevacizumab; bvczm; cerebrospinal fluid; vascular endothelial growth factor; vascular endothelial growth factor receptor 2