VEGF/VEGFR-2 changes in frontal cortex, choroid plexus, and CSF after chronic obstructive hydrocephalus.
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.
Yang
Jun
J
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.
Dombrowski
Stephen M
SM
Deshpande
Abhishek
A
Krajcir
Natalie
N
Luciano
Mark G
MG
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*
D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2