Brain regional angiogenic potential at the neurovascular unit during normal aging

Abstract

Given strong regional specialization of the brain, cerebral angiogenesis may be regionally modified during normal aging. To test this hypothesis, expression of a broad cadre of angiogenesis-associated genes was assayed at the neurovascular unit (NVU) in discrete brain regions of young vs. aged mice by laser capture microdissection coupled to quantitative real-time PCR. Complementary quantitative capillary density/branching studies were performed as well. Effects of physical exercise were also assayed to determine if age-related trends could be reversed. Additionally, gene response to hypoxia was probed to highlight age-associated weaknesses in adapting to this angiogenic stress. Aging impacted resting expression of angiogenesis-associated genes at the NVU in a region-dependent manner. Physical exercise reversed some of these age-associated gene trends, as well as positively influenced cerebral capillary density/branching in a region-dependent way. Lastly, hypoxia revealed a weaker angiogenic response in aged brain. These results suggest heterogeneous changes in angiogenic capacity of the brain during normal aging, and imply a therapeutic benefit of physical exercise that acts at the level of the NVU.

Caloric restriction confers persistent anti-oxidative, pro-angiogenic, and anti-inflammatory effects and promotes anti-aging miRNA expression profile in cerebromicrovascular endothelial cells of aged rats

“…Previous studies demonstrate that advanced aging is associated with a progressive deterioration of microvascular homeostasis due to age-related impairment of angiogenic processes (2,4,66,71,80). It is assumed that these changes have a key role in age-related microvascular rarefaction (79), decreasing tissue blood supply and impairing adaptation to hypoxia (8,41,57). Our present findings extend the results of previous studies (87) showing that aging impairs angiogenic processes in CMVECs, including endothelial cell proliferation, endothelial adhesiveness, and capillary morphogenesis (Figs.…”

Exercise Training Could Improve Age-Related Changes in Cerebral Blood Flow and Capillary Vascularity through the Upregulation of VEGF and eNOS

“…At the level of the cerebral microvessels, both the capillary density of distinct brain regions and the ultrastructure of the capillary walls are prone to age-related alterations [29]. Several groups have reported this reduction in cerebral capillary density in both humans [30, 31] and experimental animals [32–34]. The current data also demonstrated that the aging animal groups had a significantly lower brain capillary vascularity, as measured by an index of capillary density, compared with the young group (Figure 4).…”

Benefits of Physical Exercise on the Aging Brain: The Role of the Prefrontal Cortex

“…Physical exercise has been shown to promote angiogenesis (15,16), neurogenesis (17) (see also the neurogenic reserve hypothesis ) (18), and synaptogenesis (19) and to modulate central and peripheral levels of key neurochemicals, such as insulin like growth factor 1 and brain-derived neurotrophic factor (20). Physical exercise also induces structural and functional changes across different brain regions, as revealed by neuroimaging findings in response to specific physical exercise interventions (21–23).…”