Blood Biomarkers of Parenchymal Damage in Ischemic Stroke Patients Treated With Revascularization Therapies

Abstract

Purpose: Postischemic reperfusion injury may exacerbate cerebral damage and capillary dysfunction, leading to brain edema (BE), hemorrhagic transformation (HT), necrosis, and injury from free radicals with subsequent infarct growth (IG). Several plasmatic biomarkers involved in the ischemic cascade have been studied in relation to radiological and clinical outcomes of reperfusion injury in ischemic stroke with heterogeneous results. This article provides a brief overview of the contribution of circulating biomarkers to the pathophysiology of parenchymal damage in ischemic stroke patients treated with revascularization therapies. Methods: We included full reports with measurements of plasma markers in patients with acute ischemic stroke treated with revascularization therapies. Findings: Our research included a large number of observational studies investigating a possible role of circulating biomarkers in the development of parenchymal damage after acute stroke treatments. To make the results clearer, we divided the review in 4 sections, exploring the relation of different biomarkers with each of the indicators of parenchymal damage (HT, BE, IG, recanalization). Discussion and conclusion: Definite conclusions are difficult to draw because of heterogeneity across studies. However, our review seems to confirm an association between some circulating biomarkers (particularly matrix metalloproteinase-9) and occurrence of parenchymal damage in ischemic stroke patients treated with revascularization therapies.

Hemorrhagic Transformation in Ischemic Stroke and the Role of Inflammation

“…Several protein and transcription biomarkers have been evaluated to predict the risk of HT. This includes plasma cellularfibronectin (c-Fn), a major component of extracellular matrix involved in wound healing and cell adhesion (122); MMPs (122,123); neutrophil and lymphocyte counts (117,123); ferritin (123), vascular adhesion molecule−1 (VAP-1), and IL-10 that are associated with alteplase induced HT (124,125). Additionally, inflammatory markers such as TNF, C-reactive protein and homocysteine are associated with the risk and severity of HT (126).…”

“…Additionally, inflammatory markers such as TNF, C-reactive protein and homocysteine are associated with the risk and severity of HT (126). Fibrinolysis inhibitors [PAI-1, lipoprotein(a), thrombinactivated fibrinolysis inhibitor (TAFI), and homocysteine] may help to predict sICH after thrombolysis (69,122,124).…”

Metabolome Changes in Cerebral Ischemia

“…Cerebral ischemia can be caused by hypoperfusion or cessation of cerebral perfusion due to (i) embolic or thrombotic occlusion of a cerebral artery inducing a localized stroke, (ii) cardiac arrest causing global cerebral hypoxia, or (iii) delayed cerebral ischemia in the setting of vasospasm following subarachnoid hemorrhage (SAH) [16][17][18][19][20]. Depending on the size, location, and duration of cerebral ischemia, irreversible damage of neuronal cells is established within 5-10 min after cessation of cerebral perfusion [4].…”

Research Article Analysis of microRNAs -15b, -16, -21, -221 and -222 as molecular markers in the blood of rats submitted to focal cerebral ischemia associated with alcoholism

“…During the reperfusion, the restoration of blood flow worsens the tissue lesion and causes intense inflammatory response represented by the increase of reactive oxygen species (ROS), vascular endothelial lesions, increased vascular permeability and activation of platelets, neutrophils and cytokines (Stegner et al, 2019;Yang et al, 2019). Also, after stroke, cerebral edema occurs, which is one of the most relevant and responsible causes of neuronal death, as well as the development of brain lesions (Shamsaei et al, 2015;Piccardi et al, 2019). Thus, the pathology of cerebral I/R injury involves intense immune response, inflammation and cell death (Kriz et al, 2006;Piccardi et al, 2019).…”

“…Also, after stroke, cerebral edema occurs, which is one of the most relevant and responsible causes of neuronal death, as well as the development of brain lesions (Shamsaei et al, 2015;Piccardi et al, 2019). Thus, the pathology of cerebral I/R injury involves intense immune response, inflammation and cell death (Kriz et al, 2006;Piccardi et al, 2019).…”