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Pathological Role of Two Chemokines RANTES and MIF in Ischemic Stroke
Author(s) -
Liu YuChuan,
Tang SungChun,
Liou HoungChi,
Tu HuangJu,
Kang KaiHsiang,
Liou HorngHuei,
Jeng JiannShing,
Fu WenMei
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.659.19
Subject(s) - medicine , macrophage migration inhibitory factor , stroke (engine) , chemokine , evans blue , blood–brain barrier , cytokine , pharmacology , anesthesia , inflammation , immunology , central nervous system , mechanical engineering , engineering
WHO reported that around 15 million people have a stroke worldwide every year. Among them, ischemic stroke accounts for about 80 percent in all cases, but the treatment of ischemic stroke is still limited to tPA injection. Therefore, developing the new strategy to treat stroke is important and urgent. Cytokines and chemokines were found to contribute to the infarct size in stroke. This study aimed to find out the pathological roles of two chemokines, Macrophage migration inhibitory factor (MIF) and Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) in stroke. In our study, the human blood samples from stroke patients before and after tPA injection were evaluated by human cytokine array and ELISA kits. Wistar rats were subjected to transient middle cerebral artery occlusion (tMCAo) and treated with MIF or RANTES via femoral vein injection right after tMCAo. Twenty‐four hours after tMCAo, the infarct volume was evaluated by TTC staining and the neurological function was determined by the modified set of the mNSS. In addition, the blood‐brain barrier (BBB) of tMCAo rat was evaluated by Evans blue dye. Primary neuron and adult rat brain endothelial cell (ARBEC) were also subjected to oxygen‐glucose deprivation (OGD)/reoxygenation to examine the cell viability or BBB integrity after treatment of MIF or RANTES. In patients, the concentrations of MIF and RANTES were significantly increased following ischemic stroke before tPA injection. In Wistar rats, the exogenous administration of MIF (3.3 μg/kg) after tMCAo significantly increased the infarct volume; however, the RANTES‐treated (10 μg/kg) rats decreased infarct size after ischemia/reperfusion. To investigate how MIF and RANTES influence the outcome after ischemic stroke, we examined the BBB permeability after tMCAo. It was found that MIF increased the BBB permeability; however, RANTES reduced the BBB leakage after ischemia/reperfusion. In ARBEC culture also showed that MIF increased, but RANTES reduced the BBB leakage after OGD/reoxygenation. In conclusion, the levels of MIF and RANTES were elevated after ischemia. MIF increased the neuron damage in tMCAo rats; in contrast, RANTES exerts a neuroprotective effect after tMCAo. Our study indicates that MIF and RANTES may be a good drug target for developing drugs for the treatment of ischemic stroke. Support or Funding Information This work was supported by the Ministry of Science and Technology grants, 104‐2321‐B‐002‐033, Taiwan.