Neuroprotection in stroke by complement inhibition and immunoglobulin therapy

T. V. Arumugam, T. M. Woodruff, J. D. Lathia, P. K. Selvaraj, M. P. Mattson, S. M. Taylor

Research output: Contribution to journalArticle

Abstract

Activation of the complement system occurs in a variety of neuroinflammatory diseases and neurodegenerative processes of the CNS. Studies in the last decade have demonstrated that essentially all of the activation components and receptors of the complement system are produced by astrocytes, microglia, and neurons. There is also rapidly growing evidence to indicate an active role of the complement system in cerebral ischemic injury. In addition to direct cell damage, regional cerebral ischemia and reperfusion (I/R) induces an inflammatory response involving complement activation and generation of active fragments, such as C3a and C5a anaphylatoxins, C3b, C4b, and iC3b. The use of specific inhibitors to block complement activation or their mediators such as C5a, can reduce local tissue injury after I/R. Consistent with therapeutic approaches that have been successful in models of autoimmune disorders, many of the same complement inhibition strategies are proving effective in animal models of cerebral I/R injury. One new form of therapy, which is less specific in its targeting of complement than monodrug administration, is the use of immunoglobulins. Intravenous immunoglobulin (IVIG) has the potential to inhibit multiple components of inflammation, including complement fragments, pro-inflammatory cytokine production and leukocyte cell adhesion. Thus, IVIG may directly protect neurons, reduce activation of intrinsic inflammatory cells (microglia) and inhibit transendothelial infiltration of leukocytes into the brain parenchyma following an ischemic stroke. The striking neuroprotective actions of IVIG in animal models of ischemic stroke suggest a potential therapeutic potential that merits consideration for clinical trials in stroke patients.

Original languageEnglish (US)
Pages (from-to)1074-1089
Number of pages16
JournalNeuroscience
Volume158
Issue number3
DOIs
StatePublished - Feb 6 2009
Externally publishedYes

Keywords

  • apoptosis
  • brain injury
  • complement
  • ischemic stroke
  • IVIG
  • neuron

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Arumugam, T. V., Woodruff, T. M., Lathia, J. D., Selvaraj, P. K., Mattson, M. P., & Taylor, S. M. (2009). Neuroprotection in stroke by complement inhibition and immunoglobulin therapy. Neuroscience, 158(3), 1074-1089. https://doi.org/10.1016/j.neuroscience.2008.07.015