Impact of the neutrophil response to granulocyte colony-stimulating factor on the risk of hemorrhage when used in combin
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RESEARCH
JOURNAL OF NEUROINFLAMMATION
Open Access
Impact of the neutrophil response to granulocyte colony-stimulating factor on the risk of hemorrhage when used in combination with tissue plasminogen activator during the acute phase of experimental stroke Sophie Gautier1*†, Thavarak Ouk1†, Madjid Tagzirt2, Catherine Lefebvre1,3, Maud Laprais1, Olivier Pétrault1, Annabelle Dupont2, Didier Leys3 and Régis Bordet1
Abstract Background: Granulocyte colony-stimulating factor (G-CSF) is a pharmacologic agent inducing neutrophil mobilization and a new candidate for neuroprotection and neuroregeneration in stroke. Its effects when used in combination with tissue plasminogen activator (tPA) were explored during the acute phase of ischemic stroke. Methods: We used a middle cerebral artery occlusion (MCAO) model of cerebral ischemia, associated with treatment with tPA, in male spontaneously hypertensive rats (SHR). Granulocyte colony-stimulating factor (G-CSF; 60 μg/kg) was injected just before tPA. Neutrophil response in peripheral blood and in the infarct area was quantified in parallel to the infarct volume. Protease matrix metallopeptidase 9 (MMP-9) release from circulating neutrophils was analyzed by immunochemistry and zymography. Vascular reactivity and hemorrhagic volume in the infarct area was also assessed. Results: Twenty four hours after ischemia and tPA, G-CSF administration induced a significant increase of neutrophils in peripheral blood (P
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