Abstract
The arteriosclerosis-dependent alteration of brain perfusion is one of the major determinants in small vessel disease, since small vessels have a pivotal role in the brain’s autoregulation. Nevertheless, as far as we know, endothelium distress can potentiate the flow dysregulation and lead to subcortical vascular dementia that is related to small vessel disease (SVD), also being defined as subcortical vascular dementia (sVAD), as well as microglia activation, chronic hypoxia and hypoperfusion, vessel-tone dysregulation, altered astrocytes, and pericytes functioning blood-brain barrier disruption. The molecular basis of this pathology remains controversial. The apparent consequence (or a first event, too) is the macroscopic alteration of the neurovascular coupling. Here, we examined the possible mechanisms that lead a healthy aging process towards subcortical dementia. We remarked that SVD and white matter abnormalities related to age could be accelerated and potentiated by different vascular risk factors. Vascular function changes can be heavily influenced by genetic and epigenetic factors, which are, to the best of our knowledge, mostly unknown. Metabolic demands, active neurovascular coupling, correct glymphatic process, and adequate oxidative and inflammatory responses could be bulwarks in defense of the correct aging process; their impairments lead to a potentially catastrophic and non-reversible condition.
Highlights
Cerebral small vessel disease (SVD) primarily distresses the small perforating arteries, being defined as vessels with less than 50 μm diameters, defined as “all the vessels within the brain parenchyma plus the vessels with a diameter less than 500 μm in the leptomeningeal space” supplying the deep brain structures [1,2]
The immobility of the fluid drainage can support perivascular spaces (PVS)’s role in different diseases: the possible explanation of the PVS involvement in SVD, is the argued relationship demonstrated between an altered cerebrovascular reactivity (CVR), which is the change in cerebral blood flow in response to a vaso-active stimulus in the so-called neurovascular coupling, the found blood-brain barrier (BBB) dysfunction, and the correspondent perivascular inflammation [86]
HIF-1α leads to the expression of a large number of genes. It regulates more than 2% of the genes in human vascular endothelial cells [197] and is recognized today as a regulator of the vast majority of hypoxia-inducible genes that are responsible for the cell adaptation to hypoxia, including angiogenesis, anaerobic metabolism, mitochondrial biogenesis, erythropoiesis, vasomotor control, and cell proliferation, such as vascular endothelial growth factor (VEGF), glucose transporter-1 (GLUT-1), and erythropoietin (EPO), all factors that lead to survival under hypoxic conditions [198,199]
Summary
Cerebral small vessel disease (SVD) primarily distresses the small perforating arteries, being defined as vessels with less than 50 μm diameters, defined as “all the vessels within the brain parenchyma plus the vessels with a diameter less than 500 μm in the leptomeningeal space” supplying the deep brain structures [1,2]. SVD is the most important and common cause of vascular dementia, leading to 45% of dementia, and it accounts for about 20–30% of all strokes worldwide, 25% of ischemic (or lacunar strokes). It significantly increases the risk of future stroke [4]. Different hereditary forms of cerebral SVD have been described [6] In the latter forms, several pathological changes to the vasculature in small arterioles (like vascular muscle dysfunction, lipohyalinosis, vascular remodeling, and the deposition of fibrotic material) have been identified. In this case cause, structural variations, such as concentric splitting, loss of smooth muscle cells, and fibrinoid necrosis, which may increase the propensity for vessel rupture and, hemorrhage, have been seen [8,9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
