Hemorrhagic Transformation in Ischemic Stroke and the Role of Inflammation

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.

Keywords: aging; diabetes; hemorrhagic transformation; hypertension; inflammation; ischemic stroke; reperfusion therapy.

Figure 1

Immune pathways contributing to BBB disruption and subsequent HT after AIS. BBB, blood-brain barrier; IGF-1, insulin-like growth factor 1IL, interleukin; MCP-1, monocyte chemoattractant protein 1; MMP, matrix metalloproteinase; NF-κB, nuclear factor-κB; NLRP3, NOD-, LRR- and pyrin domain-containing protein 3; PAI-1, plasminogen activator inhibitor-1; ROS, reactive oxygen species; TLR, toll like receptor; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factor.