Tissue-type plasminogen activator and MRI features of cerebral small vessel disease

Abstract

Introduction. Сerebral small vessel disease (SVD) is a one of the leading causes of cognitive decline, and of ischemic and hemorrhagic stroke. It is diagnosed with the MRI criteria elaborated by international society (STRIVE, 2013). The development of SVD is closely related with endothelial dysfunction. Of special importance are studies of factors produced by endothelium and participating in the pathogenesis of SVD. Objective: to clarify the relationships of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) with MRI signs of SVD. Materials and methods. Seventy-one patients (23 males and 48 females, mean age 60.56.9) with SVD diagnosed according to the STRIVE criteria were examined. Arterial hypertension of grade 1 was revealed in 12 patients, grade 2 in 7, and grade 3 in 37 patients. White matter hyperintensities (WMH), according to Fazekas (F) scale, were graded stage F1 in 17 patients, F2 in 23, and F3 in 30 patients. Control group comprised 21 age- and sex-matched individuals with normal brain MRI. Brain MRI (3 Tl) was performed in all patients, with the assessment of the following SVD features: WMH, lacunes, microbleeds, and enlarged perivascular spaces. Blood levels of t-PA and PAI-1 were measured by enzyme immunoassay. An ANOVA variance analysis was used (p0.05). Results. High t-PA level was associated with more severe WMHs assessed with Fazekas stages (p=0.000) and with larger volume of WMH (p=0.019), as well as with the size of subcortical and semioval perivascular spaces (p=0.001). This dependence was not related with the presence arterial hypertension or its characteristics (p0.05). PAI-1 levels were not associated (p0.05) with t-PA levels or MRI features of SVD. Conclusion. The determined effect of t-PA level on the severity of WMH and perivascular spaces, the SVD features associated with increased blood-brain permeability, confirms the role of endothelial dysfunction in the development of SVD and the involvement of t-PA in the mechanisms of brain injury.

Keywords

• cerebral small vessel disease
• white matter hyperintensities
• tissue-type perivascular spaces
• endothelial dysfunction
• tissue-type plasminogen activator (t-pa)
• blood-brain barrier