Hemorrhagic Transformation in Ischemic Stroke and the Role of Inflammation.

Elena Spronk,Twinkle Joy,Joseph Kamtchum-Tatuene,Danielle Munsterman,Glen C Jickling,Sarina Falcione,Gina Sykes

doi:10.3389/fneur.2021.661955

Abstract

Hemorrhagic transformation (HT) is a common complication in patients with acute ischemic stroke. It occurs when peripheral blood extravasates across a disrupted blood brain barrier (BBB) into the brain following ischemic stroke. Preventing HT is important as it worsens stroke outcome and increases mortality. Factors associated with increased risk of HT include stroke severity, reperfusion therapy (thrombolysis and thrombectomy), hypertension, hyperglycemia, and age. Inflammation and the immune system are important contributors to BBB disruption and HT and are associated with many of the risk factors for HT. In this review, we present the relationship of inflammation and immune activation to HT in the context of reperfusion therapy, hypertension, hyperglycemia, and age. Differences in inflammatory pathways relating to HT are discussed. The role of inflammation to stratify the risk of HT and therapies targeting the immune system to reduce the risk of HT are presented.

Highlights

Hemorrhagic transformation (HT) is a common complication of ischemic stroke that is often exacerbated by reperfusion with alteplase or endovascular therapy (EVT) [1]
Clinical features associated with an increased risk of HT in patients with ischemic stroke include advanced age, stroke severity (NIHSS), hypertension, hyperglycemia, poor collaterals, early infarction on brain imaging, low platelet count, use of antithrombotic drugs, and reperfusion therapy [15]
Hypertension is associated with an increase in blood levels of pro-inflammatory cytokines such as tumor necrosis factor (TNF), IL6, monocyte chemoattractant protein-1(MCP-1), and soluble intercellular adhesion molecule (sICAM)-1 which can contribute to blood brain barrier (BBB) disruption [80]

Summary

Introduction

Hemorrhagic transformation (HT) is a common complication of ischemic stroke that is often exacerbated by reperfusion with alteplase (recombinant tissue plasminogen activator) or endovascular therapy (EVT) [1]. Clinical features associated with an increased risk of HT in patients with ischemic stroke include advanced age, stroke severity (NIHSS), hypertension, hyperglycemia, poor collaterals, early infarction on brain imaging, low platelet count, use of antithrombotic drugs, and reperfusion therapy [15]. BBB, blood-brain barrier; E-selectin, endothelial-leukocyte adhesion molecule 1; HMGB1, high mobility group box protein 1; ICAM-1, intercellular adhesion molecule-1; IL, interleukin; MMP, matrix metalloproteinase; NF-κB, nuclear factor-κB; NLRP3, NOD-, LRR- and pyrin domain-containing protein 3; NVU, neurovascular unit; PAI-1, plasminogen activator inhibitor-1; sICAM, soluble intercellular adhesion molecule; T2DM, type 2 diabetes; TNF, tumor necrosis factor; tPa, tissue plasminogen activator; VCAM-1, vascular cell adhesion molecule 1.

Results

Conclusion