Abstract

Cerebral small vessel disease (SVD) is one of the leading causes of cognitive impairment and stroke. The importance of endothelial dysfunction and high blood–brain barrier (BBB) permeability in pathogenesis, together with ischemia, is under discussion. The aim of this study was to clarify the relationship between tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1), and magnetic resonance imaging (MRI) signs of SVD. We examined 71 patients (23 men and 48 women; mean age: 60.5 ± 6.9 years) with clinical and MRI signs of SVD, and 21 healthy volunteers with normal MRIs. All subjects underwent 3T MRI and measurements of t-PA and PAI-1 levels. An increase in t-PA level is correlated with the volume of white matter hyperintensities (WMH) (R = 0.289, p = 0.034), severity on the Fazekas scale (p = 0.000), and with the size of subcortical (p = 0.002) and semiovale (p = 0.008) perivascular spaces. The PAI-1 level is not correlated with the t-PA level or MRI signs of SVD. The correlation between t-PA and the degree of WMH and perivascular spaces’ enlargement, without a correlation with PAI-1 and lacunes, is consistent with the importance of t-PA in BBB disruption and its role in causing brain damage in SVD.

Highlights

  • Cerebral small vessel disease (SVD) is associated with age and vascular risk factors, and is one of the leading causes of cognitive impairment, and ischemic and hemorrhagic strokes [1]

  • Given the technical limitations in visualizing small vessels, SVD is diagnosed in patients with clinical symptoms of SVD based on magnetic resonance imaging (MRI) signs of brain damage

  • The patterns identified in the signs of SVD associated with increased blood–brain barrier (BBB) permeability [26,27] indicate the involvement of tissue plasminogen activator (t-PA) in this process

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Summary

Introduction

Cerebral small vessel disease (SVD) is associated with age and vascular risk factors, and is one of the leading causes of cognitive impairment, and ischemic and hemorrhagic strokes [1]. Given the technical limitations in visualizing small vessels, SVD is diagnosed in patients with clinical symptoms of SVD based on magnetic resonance imaging (MRI) signs of brain damage. These include white matter hyperintensities (WMH), recent small subcortical infarcts, lacunes, microbleeds, enlarged perivascular spaces, and atrophy [2]. Studies have established a link between the total SVD score on MRI and cognitive impairment, risk of recurrent stroke, and mortality after stroke [3,4,5].

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