Dissociation between Vascular Endothelial Growth Factor Receptor-2 and Blood Vessel Density in the Caudate Nucleus after Chronic Hydrocephalus

Abstract

Chronic hydrocephalus (CH) is characterized by the presence of ventricular enlargement, decreased cerebral blood flow (CBF), and brain tissue oxygen delivery. Although the underlying pathophysiological role of vascular endothelial growth factor (VEGF) is not clear, ischemic-hypoxic events in CH are known to trigger its release. Previously, we have shown increased VEGF receptor-2 (VEGFR-2) and blood vessel density (BVd) in the hippocampus after CH. We investigated changes in neuronal and glial VEGFR-2 density and BVd in the caudate nucleus in an experimental model of CH. Animals with CH were divided into short term (ST, 2 to 4 weeks) and long term (LT, 12 to 16 weeks) and were compared with surgical controls (SCs, 12 to 16 weeks). The cellular and BVds were estimated using immunohistochemical and stereological counting methods. Overall, percentage (%)VEGFR-2 neurons were approximately two times greater in CH (ST, LT) than in SC. By comparison, glial cell %VEGFR-2 was greater by 10% to 17% in ST and 4% to 11% lower in LT compared with that in SC. Blood vessel density was significantly lower in CH than in SC in the superficial caudate. Changes in cerebrospinal fluid ventricular volume and pressure, as well as in CBF did not correlate with either VEGFR-2 or BVd. These observed findings suggest that destructive forces may outweigh angiogenic forces and possibly show a disassociation between VEGFR-2 and BV expressions.

Nonsurgical therapy for hydrocephalus: a comprehensive and critical review

“…In a dog model of chronic hydrocephalus, significant decreases in frontal cortex VEGFR-2 were reported; VEGF was not altered in tissue, but it increased in the CSF [ 223 ]. In the same dogs, VEGFR-2 increased in the hippocampus; this corresponded to increased blood vessel density, which was not seen in frontal cerebrum [ 224 ]. This is of interest because typically the hippocampus sustains only minimal direct damage in hydrocephalic brains (although there is considerable damage to the connecting pathways) [ 225 ].…”

VEGF Signaling in Neurological Disorders

“…However, those in prenatal conditions or foetal-onset hydrocephalus have shown a limited surgical treatment managing flow of cerebrospinal fluid and that potential novel treatments have been limited until recently [ 38 , 40 ]. The timing of VEGF inhibition in early stage of ischemic or hemorrhagic stroke and that of pro-VEGF therapy in the stroke recovery phase following acute ischemia after SAH echoes the significance of VEGF signaling at a different pathogenic stage, age and concentration in hydrocephalus [ 12 , 16 , 41 , 42 ].…”

VEGF/VEGFR-2 changes in frontal cortex, choroid plexus, and CSF after chronic obstructive hydrocephalus

“…The present study represents a continuation of our previous investigations of cerebrovascular and CBF changes and VEGF/VEGFR-2 responses in CH[4, 6, 7, 17]. Consistent with our previous finding of decreased CBF[7] and short-term decrease in vascularity[6], the results demonstrated a dramatic decrease in VEGFR-2 levels in frontal cortex of ST-CH compared to surgical control animals, which was correlated with decreased CBF after induced obstructive hydrocephalus.…”

“…Previously, we have shown increased VEGFR-2 levels with corresponding increases in blood vessel density (BVD) in two periventricular areas, i.e. hippocampus and caudate nucleus[4, 17]. We also showed a decrease in short-term vascularity and CBF in frontal cortex, but lacked information concerning VEGF/VEGFR-2 expression after CH[6, 7].…”