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

Abstract

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.

Circulating IGF-1 deficiency exacerbates hypertension-induced microvascular rarefaction in the mouse hippocampus and retrosplenial cortex: implications for cerebromicrovascular and brain aging

“…Several additional mechanisms may also be considered to contribute to structural microvascular rarefaction in IGF-1 deficiency, including pericyte damage (Toth et al 2013a), increased precapillary arteriolar constriction and cessation of capillary blood flow, increased susceptibility to microemboli, platelet adhesion and macrophage activation, and formation of string vessels (Brown 2010). Further, the mechanisms underlying the exacerbation of hypertension-induced microvascular injury in IGF-1 deficiency are also likely to include hemodynamic factors (Fig.…”

Brain endothelial TAK1 and NEMO safeguard the neurovascular unit

“…Although we did not detect any obvious pathology on hemotoxylin and eosin (H&E)-and Nissl-stained sections (not depicted), immunostainings of the endothelial cell marker CD31 and of collagen IV as an integral basement membrane component demonstrated numerous empty basement membrane strands, also known as string vessels (Brown, 2010), in the CNS of Nemo /+ mice (Fig. 1 A).…”

Ultrastructural alterations of human cortical capillary basement membrane in human brain oedema

“…This causes an age-related decline in cerebral angiogenesis and results in neuronal loss. These string capillaries can re-grow by proliferation and migration of endothelial cells into empty basement membrane tubes, which provide a structural scaffold, replete with signalling molecules [7]. Castejón [21] showed thin and fragmented basement membranes with areas of focal thickening in human congenital hydrocephalus.…”