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Dissociation between vascular endothelial growth factor receptor-2 and blood vessel density in the caudate nucleus
Abhishek Deshpande1, Stephen M Dombrowski, Anna Leichliter
1Department of Neurological Surgery, Section of Pediatric and Congenital Neurological Surgery, CSF Physiology Laboratory, Neurological Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
Insights
Chronic hydrocephalus (CH) increases vascular endothelial growth factor receptor-2 (VEGFR-2) in neurons but decreases blood vessel density in the caudate nucleus. This suggests destructive forces may overcome angiogenic ones in CH.
Area of Science:
- Neuroscience
- Pathophysiology
- Vascular Biology
Background:
- Chronic hydrocephalus (CH) involves ventricular enlargement, reduced cerebral blood flow (CBF), and impaired oxygen delivery.
- Ischemic-hypoxic events in CH are known to trigger vascular endothelial growth factor (VEGF) release.
- Previous studies indicated increased VEGFR-2 and blood vessel density (BVd) in the hippocampus following CH.
Purpose of the Study:
- To investigate changes in neuronal and glial VEGFR-2 density and BVd in the caudate nucleus in an experimental model of CH.
- To compare short-term (ST) and long-term (LT) CH models with surgical controls (SCs).
Main Methods:
- Experimental model of chronic hydrocephalus.
- Immunohistochemical and stereological counting methods to estimate cellular and blood vessel densities.
- Comparison of ST (2-4 weeks) and LT (12-16 weeks) CH groups with SCs (12-16 weeks).
Main Results:
- Neuronal VEGFR-2 density was approximately two times greater in both ST and LT CH groups compared to SCs.
- Glial VEGFR-2 density was elevated in ST CH but decreased in LT CH relative to SCs.
- Blood vessel density was significantly lower in the superficial caudate nucleus of CH animals compared to SCs.
Conclusions:
- Findings suggest that destructive forces may outweigh angiogenic forces in the caudate nucleus during CH.
- A potential dissociation between VEGFR-2 expression and blood vessel expression is observed in CH.
- VEGFR-2 and BVd in the caudate nucleus did not correlate with cerebrospinal fluid volume, pressure, or CBF changes.
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.
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