Blood-brain barrier is impaired in the hippocampus of young adult spontaneously hypertensive rats

Abstract

A causative role of blood-brain barrier (BBB) impairment is suggested in the pathogenesis of vascular dementia with leakage of serum components from small vessels leading to neuronal and glial damage. We examined the BBB function of young adult spontaneously hypertensive rats (SHR) in order to determine earlier changes in the BBB in chronic hypertension. SHR and stroke-prone SHR (SHRSP) were injected with horseradish peroxidase (HRP) as an indicator of BBB function and compared with Wistar Kyoto rats (WKY). The brain tissues were further examined with cationized ferritin, a marker for evaluating glycocalyx. The staining for HRP was distributed around the vessels in the hippocampal fissure of SHR and SHRSP, but not in WKY. With electron microscopy, the extravasated reaction product of HRP appeared in abluminal pits of the endothelial cells of arterioles and within the basal lamina in the hippocampus, but not the cerebral cortex, of SHR and SHRSP. On the contrary, the reaction product of HRP was never seen in the abluminal pits of the endothelial cells or the basal lamina of vessels in WKY. The number of cationized ferritin particles binding to the endothelial cells of capillaries was decreased in the hippocampus of SHR and SHRSP, while the number decreased in the cerebral cortex of SHRSP compared with those in WKY. However, the cationized ferritin binding was preserved in the endothelial cells of the arterioles with an increased vascular permeability. These findings suggest that the chronic hypertensive state induces BBB dysfunction in the hippocampus at an early stage.

Consensus meeting: monosodium glutamate – an update

“…However, a growing body of evidence addresses alterations in BBB permeability (typically to large molecules). For example, increases in BBB permeability have been reported to accompany aging (Shah and Mooradian, 1997), Alzheimers dementia (Skoog et al, 1998;Ujiie et al, 2003), type II diabetes (Starr et al, 2003), and hypertension (Mooradian, 1988;Mayhan, 1990;Ueno et al, 2004). BBB permeability also increases with increasing plasma osmolarity (Tamaki et al, 1984), and after the administration of certain drugs (Boertje et al, 1992).…”

The expression of matrix metalloproteinase-13 is increased in vessels with blood–brain barrier impairment in a stroke-prone hypertensive model

“…Effects of genetic factors cannot be disregarded. The earlier study 4 also showed that collagen deposits were occasionally seen in the BBB-damaged vessels. In addition, Iwanaga et al 16 microdissected vascular samples from the hippocampus of SHRSP and WKY rats and examined the difference in gene expression between the vascular samples with BBB impairment of SHRSP and those without impairment of WKY, using a microarray assay.…”

“…The earlier study 4 showed that the BBB function was deteriorated in vessels located along hippocampal fissures of 3-month-old SHRSP, but not in same-age WKY rats. The present study indicated that the gene and protein expression of MMP-13 were increased in hippocampal samples in SHRSP compared with those in WKY rats and that MMP-13 was present in the cytoplasm of perivascular cells of microglia/ macrophage lineage.…”

“…1 To clarify the roles of BBB impairment in vascular dementia, we have examined BBB function in various conditions related to vascular dementia, such as hypertension, acute ischemia with reperfusion, chronic cerebral hypoperfusion and aging with or without memory deficits. [2][3][4] Consequently, among these animal models, the most localized BBB impairment was clearly seen in the hippocampus, but not the cerebral cortex, of 3-month-old spontaneously hypertensive rats (SHR), especially of 3-month-old stroke-prone SHR (SHRSP), 4 which were established by Okamoto and Aoki 5 and are described in detail elsewhere. 6,7 It is known that the neuronal loss occurs with a reduction of gray matter volume in the CA1 subfield and dentate gyrus of the hippocampus in SHR at the age of 6 months or order, indicating that SHR can be a good animal model of vascular…”

Vascular mechanisms of cognitive impairment: roles of hypertension and subsequent small vessel disease under sympathetic influences

“…8,9 Moreover, blood-brain barrier alters with aging and even in some normal brain structures such as the olfactory bulb, hippocampus and periventricular areas, [10][11][12] and bloodbrain barrier dysfunctions with the development of capillary collagenosis have been revealed not only in Binswanger disease brains, 13,14 but also spontaneously hypertensive rats and a rat model of chronic cerebral hypoperfusion. 15,16 Recently, it has been shown that the intra-cranial capillary diameter is regulated by pericyte contraction under noradrenergic and purinergic neurotransmitter influences. 17 All the above findings suggest that a failure in autonomic control of cerebral circulation and damage in blood-brain barrier under untreated hypertension have significant roles in the pathogenesis of MCI/vascular cognitive impairment.…”