<sec>
<title>Background and Purpose—</title>

oxLDL (oxidized low-density lipoprotein) has been known for its potential to induce endothelial dysfunction and used as a major serological marker of oxidative stress. Recently, LOX-1 (lectin-like oxidized low-density lipoprotein receptor-1), a lectin-like receptor for oxLDL, has attracted attention in studies of neuronal apoptosis and stroke. We aim to investigate the impact of
<italic>LOX-1</italic>
-deficiency on spontaneous hypertension-related brain damage in the present study.



</sec>
<sec>
<title>Methods—</title>

We generated a
<italic>LOX-1</italic>
deficient strain on the genetic background of stroke-prone spontaneously hypertensive rat (SHRSP), an animal model of severe hypertension and spontaneous stroke. In this new disease model with stroke-proneness, we monitored the occurrence of brain abnormalities with and without salt loading by multiple procedures including
<italic>T</italic>

_{<italic>2</italic>}

weighted magnetic resonance imaging and also explored circulatory miRNAs as diagnostic biomarkers for cerebral ischemic injury by microarray analysis.



</sec>
<sec>
<title>Results—</title>

Both
<italic>T</italic>

_{<italic>2</italic>}

weighted magnetic resonance imaging abnormalities and physiological parameter changes could be detected at significantly delayed timing in
<italic>LOX-1</italic>
knockout rats compared with wild-type SHRSP, in either case of normal rat chow and salt loading (
<italic>P</italic>
&lt;0.005 in all instances; n=11–20 for SHRSP and n=13–23 for
<italic>LOX-1</italic>
knockout rats). There were no significant differences in the form of magnetic resonance imaging findings between the strains. A number of miRNAs expressed in the normal rat plasma, including rno-miR-150-5p and rno-miR-320-3p, showed significant changes after spontaneous brain damage in SHRSP, whereas the corresponding changes were modest or almost unnoticeable in
<italic>LOX-1</italic>
knockout rats. There appeared to be the lessening of correlation of postischemic miRNA alterations between the injured brain tissue and plasma in
<italic>LOX-1</italic>
knockout rats.



</sec>
<sec>
<title>Conclusions—</title>

Our data show that deficiency of LOX-1 has a protective effect on spontaneous brain damage in a newly generated
<italic>LOX-1</italic>
-deficient strain of SHRSP. Further, our analysis of miRNAs as biomarkers for ischemic brain damage supports a potential involvement of LOX-1 in blood brain barrier disruption after cerebral ischemia.



</sec>
<sec>
<title>Visual Overview—</title>

An online
<ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="visual overview">visual overview</ext-link>
is available for this article.



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