title: VEGF/VEGFR-2 changes in frontal cortex, choroid plexus, and CSF after chronic obstructive hydrocephalus.
abstract: Chronic hydrocephalus (CH) is often associated with decreased cerebral blood flow (CBF) and oxygen levels. While the exact pathophysiology is not clear, vascular endothelial growth factor (VEGF) and its receptor-2 (VEGFR-2) may be involved. Because the choroid plexus (CP) is involved in cerebrospinal fluid (CSF) production and secretes numerous growth factors including VEGF, it is important to understand VEGF/VEGFR-2 levels in the CP-CSF circulatory system. Our results showed significant decreases in CBF and VEGFR-2 levels in frontal cortex (FC) in CH compared with SC; there were no significant changes in VEGF levels. CBF change in FC was positively correlated with VEGFR-2 levels (P=0.024). Immunohistochemistry (IHC) showed robust expression of VEGF/VEGFR-2 in CP. After CH induction, ventricular CSF volume and VEGF levels significantly increased. These results suggest that the decreased VEGFR-2 levels in FC may be contributed to decreased CBF and increased ventricular CSF-VEGF levels possibly reflected a hypoxic response and/or accumulation of VEGF from CP secretion after blockage of CSF outlet. Further investigation into CSF-VEGF levels in different sites may provide a better understanding of VEGF/VEGFR-2 modulation in the normal and hydrocephalic brain, and may represent a feasible approach to potential therapeutic options for hydrocephalus.
authors.affiliation: Department of Neurological Surgery, Section of Pediatric and Congenital Neurological Surgery, CSF Physiology Laboratory, Neurological Institute, Cleveland Clinic, S-60, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Dombrowski
authors.forename: Abhishek
authors.initials: A
authors.lastname: Deshpande
authors.forename: Natalie
authors.initials: N
authors.lastname: Krajcir
authors.forename: Mark G
authors.initials: MG
authors.lastname: Luciano
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002545:Brain Ischemia / Q000134:cerebrospinal fluid / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D002831:Choroid Plexus / Q000098:blood supply / Q000378:metabolism*; D002908:Chronic Disease; D004285:Dogs; D006849:Hydrocephalus / Q000134:cerebrospinal fluid / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D007427:Intracranial Pressure; D008279:Magnetic Resonance Imaging; D008297:Male; D017397:Prefrontal Cortex / Q000098:blood supply / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics* / Q000378:metabolism*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2