Purinergic 2X7 receptor/NLRP3 pathway triggers neuronal apoptosis after ischemic stroke in the mouse

Exp Neurol. 2017 Jun:292:46-55. doi: 10.1016/j.expneurol.2017.03.002. Epub 2017 Mar 6.

Abstract

Previous research has shown that Purinergic 2X7 receptor (P2X7R) and NLRP3 inflammasome contribute to the inflammatory activation. In this study, we investigated whether P2X7R/NLRP3 pathway is involved in the caspase-3 dependent neuronal apoptosis after ischemic stroke by using a focal cortex ischemic stroke model. The expressions of P2X7R, NLRP3 inflammsome components, and cleaved caspase-3 were significantly enhanced in the ischemic brain tissue after stroke. However, the expression of cleaved caspase-3 was significantly attenuated after treatment of stroke with P2X7R antagonist (BBG) or NLRP3 inhibitor (MCC950). The treatment also significantly reduced the infarction volume, neuronal apoptosis, and neurological impairment. In addition, in vitro data also support the hypothesis that P2X7R/NLRP3 pathway plays a vital role in caspase-3 dependent neuronal apoptosis after ischemic stroke. Further investigation of effective regulation of P2X7R and NLRP3 in stroke is warranted.

Keywords: Caspase-3; Ischemic stroke; NLRP3 inflammasome; Neuronal apoptosis; P2X7 receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Apoptosis Regulatory Proteins / metabolism
  • Carrier Proteins / metabolism
  • Cells, Cultured
  • Disease Models, Animal
  • Inflammasomes / metabolism
  • Ischemia / metabolism*
  • Male
  • Mice, Inbred C57BL
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Receptors, Purinergic / metabolism
  • Signal Transduction / physiology
  • Stroke / metabolism*

Substances

  • Apoptosis Regulatory Proteins
  • Carrier Proteins
  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Receptors, Purinergic