title: Platelet-activating factor receptor (PAFR) plays a crucial role in experimental global cerebral ischemia and reperfusion.
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.
authors.affiliation: Departamento de Patologia Geral, Brazil.
authors.forename: Eliana Cristina de Brito
authors.initials: EC
authors.lastname: Toscano
authors.affiliation: Departamento de Patologia Geral, Brazil.
authors.forename: Bruno Costa
authors.initials: BC
authors.lastname: Silva
authors.affiliation: Departamento de Patologia Geral, Brazil.
authors.forename: Edna Constaza Gómez
authors.initials: EC
authors.lastname: Victoria
authors.affiliation: Departamento de Patologia Geral, Brazil.
authors.forename: Ana Clara de Souza
authors.initials: AC
authors.lastname: Cardoso
authors.affiliation: Departamento de Morfologia, Brazil.
authors.forename: Aline Silva de
authors.initials: AS
authors.lastname: Miranda
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Brazil.
authors.forename: Michelle Adriane
authors.initials: MA
authors.lastname: Sugimoto
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Brazil.
authors.forename: Lirlândia Pires
authors.initials: LP
authors.lastname: Sousa
authors.affiliation: Departamento de Patologia Geral, Brazil.
authors.forename: Bárbara Andrade de
authors.initials: BA
authors.lastname: Carvalho
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas (ICB), Brazil.
authors.forename: Lucas Miranda
authors.initials: LM
authors.lastname: Kangussu
authors.affiliation: Departamento de Patologia Geral, Brazil.
authors.forename: Daniele Gonçalves da
authors.initials: DG
authors.lastname: Silva
authors.affiliation: Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.
authors.forename: Flávia Guimarães
authors.initials: FG
authors.lastname: Rodrigues
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas (ICB), Brazil.
authors.forename: Lucíola da Silva
authors.initials: Lda S
authors.lastname: Barcelos
authors.affiliation: Departamento de Patologia Geral, Brazil.
authors.forename: Anilton César
authors.initials: AC
authors.lastname: Vasconcelos
authors.affiliation: Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.
authors.forename: Flávio Almeida
authors.initials: FA
authors.lastname: Amaral
authors.affiliation: Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.
authors.forename: Mauro Martins
authors.initials: MM
authors.lastname: Teixeira
authors.affiliation: Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, School of Medicine, University of Texas Health Science Center at Houston, TX, United States.
authors.forename: Antônio Lúcio
authors.initials: AL
authors.lastname: Teixeira
authors.affiliation: Departamento de Patologia Geral, Brazil. Electronic address: milenerachid@gmail.com.
authors.forename: Milene Alvarenga
authors.initials: MA
authors.lastname: Rachid
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000503:physiopathology; D020520:Brain Infarction / Q000209:etiology; D053148:Caspase 3 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics; D002546:Ischemic Attack, Transient / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009422:Nervous System Diseases / Q000209:etiology; D010980:Platelet Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D018709:Statistics, Nonparametric
chemical_list: D016207:Cytokines; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D053148:Caspase 3
keywords: Apoptosis; Brain; Cytokines; Inflammation; Ischemia; Mice; PAFR; Reperfusion