Platelet-activating factor receptor (PAFR) plays a crucial role in experimental global cerebral ischemia and reperfusion

Eliana Cristina de Brito Toscano, Bruno Costa Silva, Edna Constaza Gómez Victoria, Ana Clara de Souza Cardoso, Aline Silva de Miranda, Michelle Adriane Sugimoto, Lirlândia Pires Sousa, Bárbara Andrade de Carvalho, Lucas Miranda Kangussu, Daniele Gonçalves da Silva, Flávia Guimarães Rodrigues, Lucíola da Silva Barcelos, Anilton César Vasconcelos, Flávio Almeida Amaral, Mauro Martins Teixeira, Antônio Lúcio Teixeira, Milene Alvarenga Rachid

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Stroke is one of the most frequent causes of death and disability worldwide leading to a significant clinical and socioeconomic burden. Although different mechanisms are involved in the pathogenesis of stroke, inflammatory response occurs after ischemia and contributes to the expansion of brain injury. Platelet-activating factor receptor (PAF) plays crucial roles in both physiological and pathological conditions in the brain. PAF receptor (PAFR) may be expressed on cellular and nuclear membranes of various cell types, especially leukocytes, platelets, endothelial cells, neuronal cells and microglia. Herein, using mice lacking the PAFR receptor (PAFR-/-), we investigate a potential role for this receptor during experimental transient global cerebral ischemia and reperfusion (BCCAo). In PAFR deficiency, we observed a significant improvement in the neurological deficits, which were associated with a reduction of brain infarcted area as evaluated by triphenyltetrazolium chloride (TTC). Moreover, a decrease in the percentage of necrotic cavities areas and in the frequency of ischemic neurons was also found by employing histometric analysis. In addition, in PAFR-/- mice there was prevention of caspase-3 activation and decreased vascular permeability and brain edema. Decreased brain levels of the cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and the chemokine (C-X-C motif) ligand 1 (CXCL1) by ELISA were also detected in PAFR-/- BCCAo animals. Taken together, our results suggest that PAFR activation might be crucial for the global brain ischemia and reperfusion injury.

Original languageEnglish (US)
Pages (from-to)55-61
Number of pages7
JournalBrain Research Bulletin
Volume124
DOIs
StatePublished - Jun 1 2016
Externally publishedYes

Keywords

  • Apoptosis
  • Brain
  • Cytokines
  • Inflammation
  • Ischemia
  • Mice
  • PAFR
  • Reperfusion

ASJC Scopus subject areas

  • General Neuroscience

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