Disturbance of Intracerebral Fluid Clearance and Blood–Brain Barrier in Vascular Cognitive Impairment

Abstract

The entry of blood-borne macromolecular substances into the brain parenchyma from cerebral vessels is blocked by the blood–brain barrier (BBB) function. Accordingly, increased permeability of the vessels induced by insult noted in patients suffering from vascular dementia likely contributes to the cognitive impairment. On the other hand, blood-borne substances can enter extracellular spaces of the brain via endothelial cells at specific sites without the BBB, and can move to brain parenchyma, such as the hippocampus and periventricular areas, adjacent to specific sites, indicating the contribution of increased permeability of vessels in the specific sites to brain function. It is necessary to consider influx and efflux of interstitial fluid (ISF) and cerebrospinal fluid (CSF) in considering effects of brain transfer of intravascular substances on brain function. Two pathways of ISF and CSF are recently being established. One is the intramural peri-arterial drainage (IPAD) pathway of ISF. The other is the glymphatic system of CSF. Dysfunction of the two pathways could also contribute to brain dysfunction. We review the effects of several kinds of insult on vascular permeability and the failure of fluid clearance on the brain function.

Reduced Levels of Cerebrospinal Fluid/Plasma Aβ40 as an Early Biomarker for Cerebral Amyloid Angiopathy in RTg-DI Rats

“…Another noted perivascular change associated with CAA is the presence of dilated perivascular spaces, particularly around penetrating arterioles with amyloid deposition [8,24]. Although the cause of this perivascular alteration remains unclear this space contains CSF and interstitial fluid (ISF) that under normal conditions plays an important role in Aβ clearance from brain [25][26][27][28]. The presence of amyloid in these vessels promotes local perivascular inflammation and may disrupt normal CSF flow and exchange with ISF leading to enlargement of these spaces [4,29].…”

“…The CSF compartment is an important exchange reservoir with the ISF compartment that surrounds the cellular components of the brain. This dynamic interaction plays an important clearance route for Aβ and other cellular metabolic waste products through glymphatic system transport and/or alternate intramural perivascular drainage pathways [25][26][27][28]. Thus, the CSF compartment can reflect the ongoing clearance of Aβ and provide a snapshot of Aβ pathology and burden in the brain.…”

Glucose, Fructose, and Urate Transporters in the Choroid Plexus Epithelium

“…These two structures function as the interface between blood and brain fluid (i.e., brain ISF and CSF), preventing plasma proteins such as albumin and circulating blood cells (erythrocytes and leukocytes) from entering freely into the brain parenchyma. Moreover, they protect the brain from physiological fluctuations in plasma components and from blood-borne neurotoxic substances [ 1 , 2 , 3 ]. In contrast to the BBB or BCSFB, the ependymal cells that line the ventricular wall to separate the CSF from the brain ISF are interconnected with gap junctions, making them permeable to most substances, including macromolecules [ 10 ].…”

“…In addition to their barrier function, the BBB and BCSFB are also responsible for maintaining the brain microenvironment by regulating the supply of essential nutrients such as glucose and amino acids, the exchange of electrolytes between the brain ISF and the circulating blood, and the removal of metabolic wastes and neurotoxic substances such as drug metabolites and amyloid β (Aβ) [ 1 , 2 , 3 , 11 , 12 ]. To fulfill such needs, brain capillary endothelial cells and CP epithelial cells are equipped with several specific transporter proteins [ 1 , 2 , 3 ]. However, these two cells show significant dissimilarities in the expression profiles of transporters and their localization, which ultimately leads to their functional differences [ 1 , 3 , 4 ].…”

Sekundäre Neuroprotektion beim Glaukom durch ergänzende medikamentöse Therapiekonzepte

“…Beim POWG ist ein verminderter Liquordruck nachgewiesen worden [56,57] Bei neurodegenerativen Erkrankungen ist das glymphatische System mitbeteiligt [58] und führt durch eine gestörte Clearance der zerebralen Stoffwechselendprodukte zu einer Anreicherung toxischer Stoffe. Da ein enges Zusammenspiel zwischen dem glymphatischen System und der Blut-Hirn-Schranke besteht [61], führt die Kombination von Störungen in beiden Systemen zu besonders schwierigen Verläufen mit einer Minderung der zerebralen Leistungsfähigkeit [62].…”