Density of perfused brain capillaries in the aged rat during the wake-sleep cycle

Zoccoli, Giovanna; Lucchi, Maria Luisa; Andreoli, Emanuela; Lenzi, P; Franzini, Carlo

doi:10.1007/s002219900219

Cited by 8 publications

(3 citation statements)

References 4 publications

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“…However, in 1994 Villringer et al [37], using confocal laser-scanning microscopy in a closed cranial window in rat brain, found that no capillaries appeared or disappeared, and all capillaries showed perfusion within 20 seconds of fluoresein injection. Several other studies also found no reserve of non-perfused brain capillaries [38–43]. These modern findings confirm Clark’s 1918 descriptions.…”

Section: Capillaries Cannot Regulate Blood Flowby Opening and Closingsupporting

confidence: 80%

A Review of String Vessels or Collapsed, Empty Basement Membrane Tubes

Brown

2010

JAD

104

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String vessels are thin connective tissue strands, remnants of capillaries, with no endothelial cells; they do not carry blood flow. They occur in numerous species, particularly in the central nervous system, but can occur in any tissue where capillaries have died. String vessels are often associated with pathologies such as Alzheimer’s disease, ischemia, and irradiation, but are also found in normal human brains from preterm babies to the aged. They provide a record of the original blood vessel location, but gradually disappear after months or years. There have been numerous studies of string vessels (acellular capillaries) in the retina, because retinal vessels can be seen in great detail in whole mounts after trypsin digestion. Capillary regression occurs by apoptosis, synchronously along capillary segments, with macrophages engulfing apoptotic endothelial cells. Macrophages may cause the apoptosis, or the regression may be triggered by loss of the endothelial cell survival factor VEGF. VEGF expression is induced by hypoxia and promotes capillary growth. Cessation of blood flow eliminates the shear stress that helps maintain endothelial cell survival. Capillaries can re-grow by proliferation and migration of endothelial cells into empty basement membrane tubes, which provide a structural scaffold, replete with signaling molecules. This is a problem in tumor control, but useful for recovery from capillary loss. There is an age-related waning of VEGF expression in response to hypoxia. This causes an age-related decline in cerebral angiogenesis and results in neuronal loss. It may also contribute to the proposed age-related loss of brain reserve.

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Section: Capillaries Cannot Regulate Blood Flowby Opening and Closingsupporting

confidence: 80%

A Review of String Vessels or Collapsed, Empty Basement Membrane Tubes

Brown

2010

JAD

104

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“…CD31 immunostaining was followed by incubation with anti-rat biotinylated secondary antibody (diluted 1:350 in PBS + 0.2% Tween-20) for 2 min, and then alkaline phosphatase detection using the Vectastain ABC kit with NBT/BCIP as substrate (Vector Labs, Burlingame, CA). Importantly, CD31 is expressed by all endothelial cells of the vascular tree (Zhang, et al, 2002), and endogenous alkaline phosphatase is expressed by capillaries and arterioles and used to identify microvessels in the aged brain (Moody, et al, 2004; Zoccoli, et al, 2000). This combination thus leads to robust staining of the entire endothelium, even should CD31 expression diminish with age.…”

Section: Methodsmentioning

confidence: 99%

“…RNAsin ® RNAse inhibitor (Promega, Madison, WI) was added to all staining reagents. Pericytes and perivascular neuronal processes – also critical contributors to the NVU (Lok, et al, 2007) and angiogenesis (Dore-Duffy and LaManna, 2007; Lok, et al, 2007; Ward and Lamanna, 2004; Zoccoli, et al, 2000) – are contained within the perivascular space subtended by astrocyte foot-processes and were included with NVU tissue retrieved.…”

Section: Methodsmentioning

confidence: 99%

Brain regional angiogenic potential at the neurovascular unit during normal aging

Murugesan

Demarest

Madri

et al. 2012

Neurobiology of Aging

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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.

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Brain capillary perfusion in the spontaneously hypertensive rat during the wake-sleep cycle

Silvani

Bojić

Cianci

et al. 2004

Experimental Brain Research

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Hypertension is accompanied by circulatory changes in the brain and in other vascular districts; at disease onset, these changes may be largely functional and dependent on metabolic and vegetative drives. The wake-sleep cycle is a major physiological source of ultradian variability in autonomic function and in cerebral blood flow and metabolism. Aim of the study was to investigate whether sleep induces functional changes in the brain microcirculation in the developing hypertensive state. The fraction of brain capillaries perfused by plasma (perfused/anatomical capillaries) was assessed in young (8-10 weeks) spontaneously hypertensive rats (SHR) during quiet wakefulness, quiet sleep and active sleep. The density of anatomical capillaries was assessed in two groups of animals using both a histochemical method (alkaline phosphatase, AP, for morphometric measurements) and an immunofluorescence method (anti-fibronectin antibodies, FN, to detect all existing capillaries). The density of perfused capillaries was determined by intravascular injection of a fluorescent marker. The fraction of anatomical capillaries perfused by plasma was always close to maximal (0.96-0.97), without significant variations among the states of the wake-sleep cycle, and was the same for AP-stained and FN-stained sections. Data thus indicate that in this model of essential hypertension no functional changes in plasma perfusion of cerebral capillaries occur in the early stages of the disease.

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Density of perfused brain capillaries in the aged rat during the wake-sleep cycle

Cited by 8 publications

References 4 publications

A Review of String Vessels or Collapsed, Empty Basement Membrane Tubes

A Review of String Vessels or Collapsed, Empty Basement Membrane Tubes

Brain regional angiogenic potential at the neurovascular unit during normal aging

Brain capillary perfusion in the spontaneously hypertensive rat during the wake-sleep cycle

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