Pivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficits Academic Article uri icon

abstract

  • The innate immune system senses the invasion of pathogenic microorganisms and tissue injury through Toll-like receptors (TLR), a mechanism thought to be limited to immune cells. We now report that neurons express several TLRs, and that the levels of TLR2 and -4 are increased in neurons in response to IFN-gamma stimulation and energy deprivation. Neurons from both TLR2 knockout and -4 mutant mice were protected against energy deprivation-induced cell death, which was associated with decreased activation of a proapoptotic signaling cascade involving jun N-terminal kinase and the transcription factor AP-1. TLR2 and -4 expression was increased in cerebral cortical neurons in response to ischemia/reperfusion injury, and the amount of brain damage and neurological deficits caused by a stroke were significantly less in mice deficient in TLR2 or -4 compared with WT control mice. Our findings establish a proapoptotic signaling pathway for TLR2 and -4 in neurons that may render them vulnerable to ischemic death.

authors

  • Tang, S-C
  • Arumugam, TV
  • Xu, X
  • Cheng, A
  • Mughal, MR
  • Jo, DG
  • Lathia, JD
  • Siler, DA
  • Chigurupati, S
  • Ouyang, X
  • Magnus, T
  • Camandola, S
  • Mattson, MP

publication date

  • August 21, 2007