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.

Comparison of cerebrospinal fluid biomarkers between idiopathic normal pressure hydrocephalus and subarachnoid hemorrhage-induced chronic hydrocephalus: A pilot study

“…Some previous studies also reported that VEGF was increased in the CSF of patients with post-hemorrhagic hydrocephalus [6] or chronic obstructive hydrocephalus [23]. Heep et al [6] demonstrated that in neonates, the CSF VEGF levels of patients with post-hemorrhagic hydrocephalus were significantly elevated compared to those of patients with non-hemorrhagic hydrocephalus, even though the CSF VEGF levels of post-hemorrhagic and non-hemorrhagic hydrocephalus patients were increased compared to those of the non-hydrocephalic neonate controls.…”

Blood dendritic cells in cattle infected with bovine leukemia virus (BLV): isolation and phenotyping

“…The effects of VEGF are transduced mainly by two high-affinity receptors belonging to the tyrosine kinase-family: the fms-like tyrosine kinase (Flt-1) and the fetal liver kinase-1/kinase insert domain-containing receptor (Flk-1/KDR). The CP has been shown to contain mRNA (Nico et al 2004) and protein (Witmer et al 2002, Maharaj et al 2008, Yang et al 2010) of VEGF receptors.…”

Histopathological changes in the choroid plexus after traumatic brain injury in the rats: a histologic and immunohistochemical study

“…The choroid plexus shows high levels of VEGF (36), and its expression has been located on the epithelial cells (26,36,37,38). The effect of elevated VEGF levels in CSF has not been reported, although it is known that elevated VEGF levels in the brain increase the vascular permeability due to the effect of VEGF on endothelial cell junctions and fenestrations in endothelial cells.…”