Hemorrhagic Transformation after Tissue Plasminogen Activator Reperfusion Therapy for Ischemic Stroke: Mechanisms, Models, and Biomarkers

Mol Neurobiol. 2015 Dec;52(3):1572-1579. doi: 10.1007/s12035-014-8952-x. Epub 2014 Nov 4.

Abstract

Intracerebral hemorrhagic transformation (HT) is well recognized as a common cause of hemorrhage in patients with ischemic stroke. HT after acute ischemic stroke contributes to early mortality and adversely affects functional recovery. The risk of HT is especially high when patients receive thrombolytic reperfusion therapy with tissue plasminogen activator, the only available treatment for ischemic stroke. Although many important publications address preclinical models of ischemic stroke, there are no current recommendations regarding the conduct of research aimed at understanding the mechanisms and prediction of HT. In this review, we discuss the underlying mechanisms for HT after ischemic stroke, provide an overview of the models commonly used for the study of HT, and discuss biomarkers that might be used for the early detection of this challenging clinical problem.

Keywords: Blood-brain barrier; Hemorrhagic transformation; Ischemic stroke; Tissue plasminogen activator.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Astrocytes / physiology
  • Biomarkers
  • Blood-Brain Barrier / drug effects
  • Brain Ischemia / complications
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / enzymology
  • Brain Ischemia / physiopathology
  • Carboxypeptidase B2 / blood
  • Cerebral Hemorrhage / blood
  • Cerebral Hemorrhage / chemically induced
  • Cerebral Hemorrhage / etiology*
  • Chemotaxis, Leukocyte
  • Disease Models, Animal
  • Early Diagnosis
  • Endothelium, Vascular / physiopathology
  • F2-Isoprostanes / blood
  • Fibrinolytic Agents / adverse effects*
  • Fibrinolytic Agents / therapeutic use
  • Humans
  • Macrophage Activation
  • Matrix Metalloproteinases / physiology
  • Mice
  • Microglia / physiology
  • Models, Neurological
  • Nerve Tissue Proteins / physiology
  • Neuroimaging
  • Oxidative Stress
  • Plasminogen Activator Inhibitor 1 / blood
  • Thrombolytic Therapy / adverse effects*
  • Tissue Plasminogen Activator / adverse effects*
  • Tissue Plasminogen Activator / therapeutic use

Substances

  • Biomarkers
  • F2-Isoprostanes
  • Fibrinolytic Agents
  • Nerve Tissue Proteins
  • Plasminogen Activator Inhibitor 1
  • SERPINE1 protein, human
  • CPB2 protein, human
  • Carboxypeptidase B2
  • Tissue Plasminogen Activator
  • Matrix Metalloproteinases