TY - JOUR
T1 - Platelet-activating factor receptor (PAFR) plays a crucial role in experimental global cerebral ischemia and reperfusion
AU - Toscano, Eliana Cristina de Brito
AU - Silva, Bruno Costa
AU - Victoria, Edna Constaza Gómez
AU - Cardoso, Ana Clara de Souza
AU - Miranda, Aline Silva de
AU - Sugimoto, Michelle Adriane
AU - Sousa, Lirlândia Pires
AU - Carvalho, Bárbara Andrade de
AU - Kangussu, Lucas Miranda
AU - Silva, Daniele Gonçalves da
AU - Rodrigues, Flávia Guimarães
AU - Barcelos, Lucíola da Silva
AU - Vasconcelos, Anilton César
AU - Amaral, Flávio Almeida
AU - Teixeira, Mauro Martins
AU - Teixeira, Antônio Lúcio
AU - Rachid, Milene Alvarenga
N1 - Publisher Copyright:
© 2016.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Brain
KW - Cytokines
KW - Inflammation
KW - Ischemia
KW - Mice
KW - PAFR
KW - Reperfusion
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U2 - 10.1016/j.brainresbull.2016.03.022
DO - 10.1016/j.brainresbull.2016.03.022
M3 - Article
C2 - 27040712
AN - SCOPUS:84962437276
SN - 0361-9230
VL - 124
SP - 55
EP - 61
JO - Brain Research Bulletin
JF - Brain Research Bulletin
ER -