Annexin A1 attenuates neuroinflammation through FPR2/p38/COX-2 pathway after intracerebral hemorrhage in male mice

Yan Ding, Jerry Flores, Damon Klebe, Peng Li, Devin W. McBride, Jiping Tang, John H. Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

Spontaneous intracerebral hemorrhage (ICH) is the deadliest stroke subtype and neuroinflammation is a critical component of the pathogenesis following ICH. Annexin A1-FPR2 signaling has been shown to play a protective role in animal stroke models. This study aimed to assess whether Annexin A1 attenuated neuroinflammation and brain edema after ICH and investigate the underlying mechanisms. Male CD-1 mice were subjected to collagenase-induced ICH. Annexin A1 was administered at 0.5 hr after ICH. Brain water content measurement, short-term and long-term neurobehavioral tests, Western blot and immnunofluorescence were performed. Results showed that Annexin A1 effectively attenuated brain edema, improved short-term neurological function and ameliorated microglia activation after ICH. Annexin A1 also improved memory function at 28 days after ICH. However, these beneficial effects were abolished with the administration of FPR2 antagonist Boc-2. Furthermore, AnxA1/FPR2 signaling may confer protective effects via inhibiting p38-associated inflammatory cascade. Our study demonstrated that Annexin A1/FPR2/p38 signaling pathway played an important role in attenuating neuroinflammation after ICH and that Annexin A1 could be a potential therapeutic strategy for ICH patients.

Original languageEnglish
Pages (from-to)168-178
Number of pages11
JournalJournal of Neuroscience Research
Volume98
Issue number1
DOIs
StatePublished - Jan 1 2020

ASJC Scopus Subject Areas

  • Cellular and Molecular Neuroscience

Keywords

  • Annexin A1
  • RRID:AB_2085144
  • RRID:AB_2533983
  • RRID:AB_305641
  • RRID:AB_330713
  • RRID:AB_630836
  • RRID:AB_881998
  • intracerebral hemorrhage
  • neuroinflammation
  • p38 MAPK
  • Cerebral Hemorrhage/chemically induced
  • Cyclooxygenase 2/metabolism
  • Male
  • p38 Mitogen-Activated Protein Kinases/metabolism
  • Neurons/drug effects
  • Brain Edema/drug therapy
  • Brain/drug effects
  • Collagenases
  • Animals
  • Annexin A1/pharmacology
  • Mice
  • Maze Learning/drug effects
  • Receptors, Formyl Peptide/metabolism
  • Disease Models, Animal

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