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Clin Sci (Lond). 2018 Jun 26;132(12):1315-1328. doi: 10.1042/CS20171572. Print 2018 Jun 29.

Effects of dietary salt on gene and protein expression in brain tissue of a model of sporadic small vessel disease.

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School of Life Sciences, Thomson Building, University of Glasgow, University Avenue, Glasgow G12 8QQ, U.K.
Institute of Cardiovascular and Medical Sciences, University of Glasgow, University Avenue, Glasgow G12 8QQ, U.K.
Academic Department of Neuropathology, Centre for Clinical Brain Sciences, Little France, Edinburgh EH16 4SB, U.K.
Centre for Clinical Brain Sciences, and UK Dementia Research Institute at the University of Edinburgh, Chancellors Building, 49 Little France Crescent, Edinburgh EH16 4SB, U.K.



The effect of salt on cerebral small vessel disease (SVD) is poorly understood. We assessed the effect of dietary salt on cerebral tissue of the stroke-prone spontaneously hypertensive rat (SHRSP) - a relevant model of sporadic SVD - at both the gene and protein level. Methods: Brains from 21-week-old SHRSP and Wistar-Kyoto rats, half additionally salt-loaded (via a 3-week regime of 1% NaCl in drinking water), were split into two hemispheres and sectioned coronally - one hemisphere for mRNA microarray and qRT-PCR, the other for immunohistochemistry using a panel of antibodies targeting components of the neurovascular unit. Results: We observed differences in gene and protein expression affecting the acute phase pathway and oxidative stress (ALB, AMBP, APOH, AHSG and LOC100129193, up-regulated in salt-loaded WKY versus WKY, >2-fold), active microglia (increased Iba-1 protein expression in salt-loaded SHRSP versus salt-loaded WKY, p<0.05), vascular structure (ACTB and CTNNB, up-regulated in salt-loaded SHRSP versus SHRSP, >3-fold; CLDN-11, VEGF and VGF down-regulated >2-fold in salt-loaded SHRSP versus SHRSP) and myelin integrity (MBP down-regulated in salt loaded WKY rats versus WKY, >2.5-fold). Changes of salt-loading were more pronounced in SHRSP and occurred without an increase in blood pressure in WKY rats.


Salt exposure induced changes in gene and protein expression in an experimental model of SVD and its parent rat strain in multiple pathways involving components of the glio-vascular unit. Further studies in pertinent experimental models at different ages would help clarify the short- and long-term effect of dietary salt in SVD.


SHRSP; Salt; Small Vessel; White Matter; stroke

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