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Stroke. 2009 Nov;40(11):3596-600. doi: 10.1161/STROKEAHA.109.561050. Epub 2009 Sep 10.

Attenuation of brain response to vascular endothelial growth factor-mediated angiogenesis and neurogenesis in aged mice.

Author information

1
Department of Anesthesia and Perioperative Care, University of California, Center for Cerebrovascular Research, San Francisco, Calif 94110, USA.

Erratum in

Abstract

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.

PMID:
19745179
PMCID:
PMC2783321
DOI:
10.1161/STROKEAHA.109.561050
[Indexed for MEDLINE]
Free PMC Article

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