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. 2021 Dec;36(8):2553-2566.
doi: 10.1007/s11011-021-00767-8. Epub 2021 Jun 12.

Blood-brain barrier leakage and perivascular collagen accumulation precede microvessel rarefaction and memory impairment in a chronic hypertension animal model

Esra Özkan  1   2 , Yağmur Çetin-Taş  3 , Emine Şekerdağ  3 , Ali B Kızılırmak  3 , Ali Taş  3 , Erdost Yıldız  3 , Hale Yapıcı-Eser  3   4 , Serçin Karahüseyinoğlu  3   5 , Müjdat Zeybel  3   6   7 , Yasemin Gürsoy-Özdemir  3   8
Affiliations

Blood-brain barrier leakage and perivascular collagen accumulation precede microvessel rarefaction and memory impairment in a chronic hypertension animal model

Esra Özkan et al. Metab Brain Dis. 2021 Dec.

Abstract

Hypertension (HT) is one of the main causes of vascular dementia, lead to cognitive decline. Here, we investigated the relationship between cerebral microvessels, pericytes, extracellular matrix (ECM) accumulation, blood-brain barrier (BBB) breakdown, and memory impairment at mid-life in a chronic hypertension animal model. Spontaneously hypertensive rats (SHRs) (n = 20) are chosen for the model and age matched Wistar rats (n = 16) as controls. Changes in brain microvasculature and in vitro experiments are shown with immunofluorescence studies and cognition with open field, novel object recognition, and Y maze tests. There was a significant reduction in pericyte coverage in SHRs (p = 0.021), while the quantitative parameters of the cerebral microvascular network were not different between groups. On the other hand, parenchymal albumin leakage, as a Blood-brain barrier (BBB) breakdown marker, was prominent in SHRs (p = 0.023). Extracellular matrix (ECM) components, collagen type 1, 3 and 4 were significantly increased (accumulated) around microvasculature in SHRs (p = 0.011, p = 0.013, p = 0.037, respectively). Furthermore, in vitro experiments demonstrated that human brain vascular pericytes but not astrocytes and endothelial cells secreted type I collagen upon TGFβ1 exposure pointing out a possible role of pericytes in increased collagen accumulation around cerebral microvasculature due to HT. Furthermore, valsartan treatment decreased the amount of collagen type 1 secreted by pericytes after TGFβ1 exposure. At the time of evaluation, SHRs did not demonstrate cognitive decline and memory impairments. Our results showed that chronic HT causes ECM accumulation and BBB leakage before leading to memory impairments and therefore, pericytes could be a novel _target for preventing vascular dementia.

Keywords: Blood–brain barrier; Collagen; Dementia; Pericyte; Spontaneously hypertensive rats; Valsartan.

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References

    1. Agata J et al (2004) Angiotensin II receptor blocker prevents increased arterial stiffness in patients with essential hypertension. Circ J 68(12):1194–1198. https://doi.org/10.1253/circj.68.1194 . Japan - DOI - PubMed
    1. Almutairi MMA et al (2016) Factors controlling permeability of the blood-brain barrier. Cell Mol Life Sci 73(1):57–77. https://doi.org/10.1007/s00018-015-2050-8 . Switzerland - DOI - PubMed
    1. Antunes M, Biala G (2012) The novel object recognition memory: neurobiology, test procedure, and its modifications. Cogn Process 13(2):93–110. https://doi.org/10.1007/s10339-011-0430-z - DOI - PubMed
    1. Bailey EL et al (2011) Cerebral small vessel endothelial structural changes predate hypertension in stroke-prone spontaneously hypertensive rats: a blinded, controlled immunohistochemical study of 5- to 21-week-old rats. Neuropathol Appl Neurobiol 37(7):711–726. https://doi.org/10.1111/j.1365-2990.2011.01170.x . England - DOI - PubMed
    1. Bailey EL et al (2018) Effects of dietary salt on gene and protein expression in brain tissue of a model of sporadic small vessel disease. Clin Sci (London, England : 1979) 132(12):1315–1328. https://doi.org/10.1042/CS20171572 - DOI

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