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.
Highlights
Cerebrovascular insult leads to brain tissue damage followed by cognitive impairment
blood–brain barrier (BBB) permeability to blood-borne horseradish peroxidase (HRP) was increased in the hippocampus of a Mongolian gerbil, an experimental model of acute ischemia followed by reperfusion [56]
interstitial fluid (ISF) flow has an effect on the passage of blood-borne substances in the brain parenchyma through the Circumventricular Organs (CVOs) and choroid plexus
Summary
Cerebrovascular insult leads to brain tissue damage followed by cognitive impairment. Some reports indicate that damage of the blood–brain barrier (BBB) in cerebral vessels plays a role in the pathogenesis of vascular dementia caused by multiple lacunes with endothelial necrosis and leukoaraiosis with perivascular collagen deposition [2,3,4,5]. It remains unclear which insult has an effect on the BBB function, or whether there are regional differences in the severity of BBB damage caused by exposure of the insult. We review the functions of BBB and blood–cerebrospinal fluid (CSF) barrier (BCSFB) and intracerebral fluid clearance, and the effects of several kinds of insult on vascular permeability
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