Biphasic actions of HMGB1 signaling in inflammation and recovery after stroke

Ann N Y Acad Sci. 2010 Oct:1207:50-7. doi: 10.1111/j.1749-6632.2010.05728.x.

Abstract

Stroke induces a complex web of pathophysiology that may evolve over hours to days and weeks after onset. It is now recognized that inflammation is an important phenomenon that can dramatically influence outcomes after stroke. In this minireview, we explore the hypothesis that inflammatory signals after stroke are biphasic in nature. The high-mobility group box 1 (HMGB1) protein is discussed as an example of this idea. HMGB1 is normally present in the nucleus. Under ischemic conditions, it is released extracellularly from many types of cells. During the acute phase poststroke, HMGB1 promotes necrosis and influx of damaging inflammatory cells. However, during the delayed phase poststroke, HMGB1 can mediate beneficial plasticity and recovery in many cells of the neurovascular unit. These emerging findings support the hypothesis that inflammation after stroke can be both detrimental and beneficial, depending on the cellular situations involved.

Publication types

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

MeSH terms

  • Animals
  • Extracellular Space / physiology
  • HMGB1 Protein / physiology*
  • Humans
  • Inflammation / physiopathology*
  • Models, Neurological
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / physiology
  • Signal Transduction / physiology
  • Stroke / physiopathology*
  • Toll-Like Receptor 4 / physiology

Substances

  • HMGB1 Protein
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic
  • Toll-Like Receptor 4