Tissue Plasminogen Activator and MRI Signs of Cerebral Small Vessel Disease

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.

Biomarkers of endothelial dysfunction in cerebral small vessel disease

“…. Contrary, another recent study from Moscow found that t-PA levels were associated with WMHs and EPVSs, while PAI-1 levels were not associated with cerebral SVD(Dobrynina et al, 2019). However, all patients in the Maastricht stroke study had a lacunar stroke, but only half of the patients in the Moscow study had a lacunar stroke.…”

L-Arginine-eNOS-NO Functional System in Brain Damage and Cognitive Impairments in Cerebral Small Vessel Disease

“…T-PA, along with its well-known role in fibrinolysis, has pleiotropic activities in the central nervous system-neuroplasticity, excitotoxicity, and influence on BBB permeability [57]. Previously, we established a relationship between increased t-PA levels and MRI changes associated with high BBB permeability [58]. However, there are reasons to believe that the combined effect of t-PA, NO, and its oxidation products provides a continuum of vascular and cerebral damage associated with neurodegeneration and mixed vascular-degenerative forms of the CSVD.…”

Biochemical markers of neurodegeneration in patients with cerebral small vessel disease and Alzheimer's disease

“…При МРТ-исследовании на магнитно-резонансном томографе с величиной магнитной индукции 3 Тл («Siemens Healthineers AG») оценивали МРТ-признаки ЦМА [2] и МРТ-признаки БА [4,5], исключали наличие иных МРТ-изменений. Кли-прогрессирования ЦМА [13,14], можно предполагать, что биохимические маркеры астроцитарной реакции будут наиболее подходящими кандидатами для диагностики ЦМА, ассоциированной с нейродегенерацией. Основным признанным маркером активации астроглии является глиофибриллярный кислый белок (GFAP).…”

“…В ранее проведённых исследованиях заболеваний с КР повышение GFAP в крови и ЦСЖ рассматривалось как маркер БА и ассоциировалось с патологическим астроглиозом[19][20][21][22][23][24][25][26][27]. Результаты нашего исследования свидетельствуют о GFAP как маркере ЦМА, что, учитывая определяющее значение в развитии заболевания высокой проницаемости ГЭБ[14], может объясняться реактивностью астроцитов в поддержании гомеостаза ГЭБ. О значении данного маркера для ЦМА и развития смешанных форм свидетельствуют результаты его исследования при БА[27].…”