Cerebral microbleeds (CMBs) are defined as small and hypointense areas which could correspond to clusters of hemosiderin-laden macrophages resulting from small self-limiting haemorrhages.  CMBs have been associated with aging, traumatic brain injury, stroke, and neurodegenerative disorders, among them the cerebral amyloid angiopathy. CMBs are potentially a radiological biomarker of the cerebral small vessel disease prone to bleeding and developing spontaneous intracerebral haemorrhages (ICHs).  Recently, in patients with atrial fibrillation anticoagulated after ischaemic stroke or transient ischaemic attack, the presence of CMBs was independently associated with symptomatic ICH risk, and could be used to inform anticoagulation decisions.  Failure of blood–brain barrier integrity leading to focal extravascular leakage of blood components is a decisive event in the pathogenesis of multiple sclerosis (MS), a disease characterized by multifocal demyelinated lesions within the central nervous system. Extravascular leakage of blood may have the features of radiologically measurable CMBs. Adhesion molecules participating in blood–brain barrier disruption and in inflammatory responses, supported by fibrinogen extravasation and promoting tissue factor expression,    in turn could be involved in the formation of CMBs. Vascular adhesion protein-1 (VAP-1) facilitates leukocyte infiltration into inflamed tissue through an enzymatic activity that mediates cell binding to the vessel wall. VAP-1 catalyzes formation of free radicals from its substrates on leukocytes, providing an inflammatory microenvironment and causing expression of additional adhesion molecules. VAP-1 is both a cell surface and a circulating protein, released through cleavage mechanisms that are only partially defined.  Higher plasma activity level of VAP-1 has been found both in consecutive patients with spontaneous ICH and in patients with stroke treated with tissue plasminogen activator, who subsequently experienced ICH. In animal models, VAP-1 inhibition decreased both immune cell infiltration after ICH and micro-vascular dysfunction.  Taking advantage of MS as a disease model,   we aimed at extending our knowledge about the association between plasma levels of VAP-1 and occurrence of CMBs in MS patients, assessed by magnetic resonance imaging (MRI) measures in a cross-sectional study ([Table 1] and [Supplementary Material], available in the online version). In turn, this could underline potential biological relations between CMBs and ICH.
|Titolo:||Are Plasma Levels of Vascular Adhesion Protein-1 Associated Both with Cerebral Microbleeds in Multiple Sclerosis and Intracerebral Haemorrhages in Stroke?|
ZILIOTTO, Nicole (Primo) (Corresponding)
MARCHETTI, Giovanna (Penultimo)
BERNARDI, Francesco (Ultimo)
|Data di pubblicazione:||2019|
|Appare nelle tipologie:||03.1 Articolo su rivista|