Blood‐brain barrier damage in vascular dementia

Abstract

New findings on flow or drainage pathways of brain interstitial fluid and cerebrospinal fluid have been made. The interstitial fluid flow has an effect on the passage of blood-borne substances in the brain parenchyma, especially in areas near blood-brain barrier (BBB)-free regions. Actually, blood-borne substances can be transferred in areas with intact BBB function, such as the hippocampus, the corpus callosum, periventricular areas, and medial portions of the amygdala, presumably through leaky vessels in the subfornical organs or the choroid plexus. Increasing evidence indicates that dysfunction of the BBB function may play a significant role in the pathogenesis of vascular dementia. Accordingly, we have examined which insults seen in patients suffering from vascular dementia have an effect on the BBB using experimental animal models exhibiting some phenotypes of vascular dementia. The BBB in the hippocampus was clearly deteriorated in Mongolian gerbils exposed to acute ischemia followed by reperfusion and also in stroke-prone spontaneously hypertensive rats (SHRSP) showing hypertension. The BBB in the corpus callosum was clearly deteriorated in Wistar rats with permanent ligation of the bilateral common carotid arteries showing chronic hypoperfusion. The BBB in the hippocampus and the olfactory bulb was mildly deteriorated in aged senescence accelerated prone mice (SAMP8) showing cognitive dysfunction. The BBB in the hippocampus was mildly deteriorated in aged animals with hydrocephalus. Mild endothelial damage was seen in hyperglycemic db/db mice. In addition, mRNA expression of osteopontin, matrix metalloproteinase-13 (MMP-13), and CD36 was increased in vessels showing BBB damage in hypertensive SHRSP. As osteopontin, MMP-13 and CD36 are known to be related to brain injury and amyloid β accumulation or clearance, BBB damage followed by increased gene expression of these molecules not only contributes to the pathogenesis of vascular dementia, but also bridges the gap between vascular dementia and Alzheimer's disease.

Communication from the periphery to the hypothalamus through the blood–brain barrier: An in vitro platform

“…One of the major barriers limiting the blood direct contact with the CNS is the blood-brain barrier (BBB). The BBB is built up by endothelial cells, which are interconnected by an elaborate network of tight junctions, completely encircling the lumen; perivascular endfeet of astrocytes, which cover the abluminal surface of the microvascular basement membranes; and pericytes, which have been suggested to regulate endothelial cell proliferation, survival, migration, differentiation, and vascular branching (Ballabh et al, 2004;Hellström et al, 2001;Ueno et al, 2015). Together, they form a diffusion barrier that selectively excludes most blood-borne substances from entering the brain (Martins et al, 2013).…”

Intermittent hypoxia training protects cerebrovascular function in Alzheimer's disease

“…[34][35][36] The pathology of small vessel disease includes microvascular rarefaction, [37][38][39] neurovascular dysfunction, 40 and disruption of the blood-brain barrier. 41,42 It is estimated that 60-90% of AD patients have significant cerebrovascular pathology. 43 Hainsworth and Markus 44 identified four key clinicopathologic hallmarks of cerebral small vessel disease: small, discrete infarcts within the brain, arteriopathy of small cerebral vessels, diffuse damage to the white matter, and cognitive impairment.…”

Longitudinal Performance of Senescence Accelerated Mouse Prone-Strain 8 (SAMP8) Mice in an Olfactory-Visual Water Maze Challenge

“…Ueno et al (2016) reported that the barrier properties of the olfactory bulb deteriorate in pre-clinical rodent models of dementia including SAMP8 mice, findings consistent with clinical studies that suggest deterioration in olfaction as amongst the earliest indicators of cognitive decline (Attems et al, 2015; Devanand et al, 2015; Marin et al, 2018). In SAMP8 mice, Soriano-Cantón et al (2015) reported that the B1-neural stem cells of the mouse sub-ependymal zone, which supports ongoing production of the olfactory bulb interneurons, are transiently expanded in young SAMP8 mice relative control senescent resistant SAMR1 mice.…”