Azithromycin protects mice against ischemic stroke injury by promoting macrophage transition towards M2 phenotype

Diana Amantea, Michelangelo Certo, Francesco Petrelli, Cristina Tassorelli, Giuseppe Micieli, Maria Tiziana Corasaniti, Paolo Puccetti, Francesca Fallarino, Giacinto Bagetta

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)


To develop novel and effective treatments for ischemic stroke, we investigated the neuroprotective effects of the macrolide antibiotic azithromycin in a mouse model system of transient middle cerebral artery occlusion. Intraperitoneal administration of azithromycin significantly reduced blood-brain barrier damage and cerebral infiltration of myeloid cells, including neutrophils and inflammatory macrophages. These effects resulted in a dose-dependent reduction of cerebral ischemic damage, and in a remarkable amelioration of neurological deficits up to 7 days after the insult. Neuroprotection was associated with increased arginase activity in peritoneal exudate cells, which was followed by the detection of Ym1- and arginase I-immunopositive M2 macrophages in the ischemic area at 24-48 h of reperfusion. Pharmacological inhibition of peritoneal arginase activity counteracted azithromycin-induced neuroprotection, pointing to a major role for drug-induced polarization of migratory macrophages towards a protective, non-inflammatory M2 phenotype.

Original languageEnglish
Pages (from-to)116-25
Number of pages10
JournalExperimental Neurology
Issue numberPart 1
Early online date27 Oct 2015
Publication statusPublished - Jan 2016


  • Animals
  • Anti-Bacterial Agents/pharmacology
  • Azithromycin/pharmacology
  • Brain Ischemia/drug therapy
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Macrophage Activation/drug effects
  • Macrophages/drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neuroprotective Agents/pharmacology
  • Stroke/drug therapy


Dive into the research topics of 'Azithromycin protects mice against ischemic stroke injury by promoting macrophage transition towards M2 phenotype'. Together they form a unique fingerprint.

Cite this