The acute-phase protein PTX3 is an essential mediator of glial scar formation and resolution of brain edema after ischemic injury

J Cereb Blood Flow Metab. 2014 Mar;34(3):480-8. doi: 10.1038/jcbfm.2013.224. Epub 2013 Dec 18.


Acute-phase proteins (APPs) are key effectors of the immune response and are routinely used as biomarkers in cerebrovascular diseases, but their role during brain inflammation remains largely unknown. Elevated circulating levels of the acute-phase protein pentraxin-3 (PTX3) are associated with worse outcome in stroke patients. Here we show that PTX3 is expressed in neurons and glia in response to cerebral ischemia, and that the proinflammatory cytokine interleukin-1 (IL-1) is a key driver of PTX3 expression in the brain after experimental stroke. Gene deletion of PTX3 had no significant effects on acute ischemic brain injury. In contrast, the absence of PTX3 strongly compromised blood-brain barrier integrity and resolution of brain edema during recovery after ischemic injury. Compromised resolution of brain edema in PTX3-deficient mice was associated with impaired glial scar formation and alterations in scar-associated extracellular matrix production. Our results suggest that PTX3 expression induced by proinflammatory signals after ischemic brain injury is a critical effector of edema resolution and glial scar formation. This highlights the potential role for inflammatory molecules in brain recovery after injury and identifies APPs, in particular PTX3, as important targets in ischemic stroke and possibly other brain inflammatory disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Edema / etiology
  • Brain Edema / immunology
  • Brain Edema / metabolism*
  • Brain Edema / pathology
  • Brain Ischemia / complications
  • Brain Ischemia / immunology
  • Brain Ischemia / metabolism*
  • Brain Ischemia / pathology
  • C-Reactive Protein / genetics
  • C-Reactive Protein / metabolism*
  • Cell Proliferation / drug effects
  • Cicatrix / immunology
  • Cicatrix / metabolism*
  • Cicatrix / pathology
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression / drug effects
  • Interleukin-1alpha / genetics
  • Interleukin-1alpha / immunology
  • Interleukin-1alpha / pharmacology
  • Interleukin-1beta / genetics
  • Interleukin-1beta / immunology
  • Interleukin-1beta / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neuroglia / immunology
  • Neuroglia / metabolism*
  • Neuroglia / pathology


  • Interleukin-1alpha
  • Interleukin-1beta
  • Nerve Tissue Proteins
  • neuronal pentraxin
  • C-Reactive Protein