AIM2 and NLRC4 inflammasomes contribute with ASC to acute brain injury independently of NLRP3

Adam Denes, Graham Coutts, Nikolett Lénárt, Sheena Cruickshank, Pablo Pelegrin, Joanne Skinner, Nancy Rothwell, Stuart Allan, David Brough

Research output: Contribution to journalArticlepeer-review


Inflammation that contributes to acute cerebrovascular disease is driven by the proinflammatory cytokine interleukin-1 and is known to exacerbate resulting injury. The activity of interleukin-1 is regulated by multimolecular protein complexes called inflammasomes. There are multiple potential inflammasomes activated in diverse diseases, yet the nature of the inflammasomes involved in brain injury is currently unknown. Here, using a rodent model of stroke, we show that the NLRC4 (NLR family, CARD domain containing 4) and AIM2 (absent in melanoma 2) inflammasomes contribute to brain injury. We also show that acute ischemic brain injury is regulated by mechanisms that require ASC (apoptosis-associated specklike protein containing a CARD), a common adaptor protein for several inflammasomes, and that the NLRP3 (NLR family, pyrin domain containing 3) inflammasome is not involved in this process. These discoveries identify the NLRC4 and AIM2 inflammasomes as potential therapeutic targets for stroke and provide new insights into how the inflammatory response is regulated after an acute injury to the brain.
Original languageEnglish
Pages (from-to)4050-4055
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number13
Publication statusPublished - 31 Mar 2015


  • brain injury
  • cell death
  • cerebral ischemia
  • inflammasome
  • inflammation

Research Beacons, Institutes and Platforms

  • Dementia@Manchester


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