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Updated: Jun 20, 2026
In Vitro Assays to Assess Blood-brain Barrier Mesh-like Vessel Formation and Disruption
Published on: June 20, 2017
Attenuation of brain response to vascular endothelial growth factor-mediated angiogenesis and neurogenesis in aged
Peng Gao1, Fanxia Shen, Rodney Allanigue Gabriel
1Department of Anesthesia and Perioperative Care, University of California, Center for Cerebrovascular Research, San Francisco, Calif 94110, USA.
Background And Purpose:
Alterations of neuroangiogenic response play important roles in the development of aging-related neurodisorders and affect gene-based therapies. We tested brain response to vascular endothelial growth factor (VEGF) in aged mice.
Methods:
Adeno-associated viral vector (AAV)-VEGF, an adeno-associated viral vector expressing VEGF, was injected into the brain of 3-, 12-, and 24-month-old mice. AAV-LacZ-injected mice were used as controls (n=6). Before euthanasia at 6 weeks after vector injection, the mice were intraperitoneally injected with 5-bromodeoxyuridine for 3 consecutive days. The vascular density and the number of neuroprogenitors were analyzed.
Results:
Injection of AAV-VEGF increased the vascular density in the brain of 3-, 12-, and 24-month-old mice by 22%+/-7% (AAV-VEGF: 320+/-15 per 10x field versus AAV-LacZ: 263+/-8, P<0.05), 20%+/-8 (AAV-VEGF: 300+/-9 versus AAV-LacZ: 250+/-11, P<0.05), and 7%+/-16% (AAV-VEGF: 257+/-27 versus AAV-LacZ: 236+/-13, P=0.283), respectively. There were more VEGF receptor-positive neuroprogenitors in the subventricular zone of AAV-VEGF-injected 3- (22+/-2) and 12-month-old mice (21+/-5) than that of 24-month-old mice (7+/-1). More 5-bromodeoxyuridine-positive endothelial cells and neuroprogenitors were detected around the injection site and subventricular zone of 3- (13+/-4) and 12-month-old mice (14+/-5) than that of 24-month-old mice (1+/-1). VEGF receptor 2 was upregulated in AAV-VEGF-injected brains of 3- and 12-month-old mice, but not in 24-month-old mice.
Conclusions:
The angiogenic and neurogenic response to VEGF stimulation is attenuated in the aged mouse brain, which may be due to reduced VEGF receptor activity.
