Chronic hydrocephalus-induced hypoxia: increased expression of VEGFR-2+ and blood vessel density in hippocampus

Area of Science:

• Neuroscience
• Pathophysiology
• Angiogenesis

Background:

• Chronic hydrocephalus (CH) is a neurological disorder marked by increased cerebrospinal fluid (CSF) volume and pressure, potentially impairing cognitive function.
• The exact brain insult site in CH is uncertain, but mechanisms like neural compression and hypoxia are implicated, particularly affecting the hippocampus.
• The hippocampus, crucial for memory, may be vulnerable due to its proximity to expanding CSF ventricles.

Purpose of the Study:

• To quantify the density of vascular endothelial growth factor receptor 2 (VEGFR-2) expressing cells and blood vessels in the hippocampus of a CH model.
• To investigate the relationship between VEGFR-2 expression, blood vessel density, and CH parameters like CSF volume and intracranial pressure.
• To explore the potential role of VEGFR-2 in adaptive angiogenesis in response to CH-induced hypoxia.

Main Methods:

• Utilized an established model of chronic hydrocephalus in animals.
• Employed immunohistochemistry and stereological methods to quantify VEGFR-2(+) cells and blood vessel density (BVd) in specific hippocampal regions.
• Compared cellular and vascular densities between CH animals (at different time points) and surgical controls (SC).

Main Results:

• Found a significant six- to eightfold increase in VEGFR-2(+) cell density and a more than twofold increase in BVd in the hippocampus of CH animals compared to SC.
• VEGFR-2(+) and BVd were significantly correlated with CSF volume but not intracranial pressure.
• The percentage of VEGFR-2(+) cells was significantly higher in CH animals and correlated with increased BVd.

Conclusions:

• Chronic hydrocephalus induces a substantial increase in VEGFR-2(+) cells and blood vessel density in the hippocampus.
• These vascular changes in CH are linked to CSF volume, suggesting an adaptive angiogenic response to hypoxia.
• Targeting the vascular endothelial growth factor/VEGFR-2 pathway may offer therapeutic potential for hydrocephalus and other cerebral ischemic conditions involving hypoxia.