Details

Autor(en) / Beteiligte

• Desestret, Virginie
• Riou, Adrien
• Chauveau, Fabien
• Cho, Tae-Hee
• Devillard, Emilie
• Marinescu, Marilena
• Ferrera, René
• Rey, Catherine
• Chanal, Marie
• Angoulvant, Denis
• Honnorat, Jérôme
• Nighoghossian, Norbert
• Berthezène, Yves
• Nataf, Serge
• Wiart, Marlène
• Kleinschnitz, Christoph

Titel

In vitro and in vivo models of cerebral ischemia show discrepancy in therapeutic effects of M2 macrophages

Ist Teil von

• PloS one, 2013-06, Vol.8 (6), p.e67063-e67063

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• THE INFLAMMATORY RESPONSE FOLLOWING ISCHEMIC STROKE IS DOMINATED BY INNATE IMMUNE CELLS: resident microglia and blood-derived macrophages. The ambivalent role of these cells in stroke outcome might be explained in part by the acquisition of distinct functional phenotypes: classically (M1) and alternatively activated (M2) macrophages. To shed light on the crosstalk between hypoxic neurons and macrophages, an in vitro model was set up in which bone marrow-derived macrophages were co-cultured with hippocampal slices subjected to oxygen and glucose deprivation. The results showed that macrophages provided potent protection against neuron cell loss through a paracrine mechanism, and that they expressed M2-type alternative polarization. These findings raised the possibility of using bone marrow-derived M2 macrophages in cellular therapy for stroke. Therefore, 2 million M2 macrophages (or vehicle) were intravenously administered during the subacute stage of ischemia (D4) in a model of transient middle cerebral artery occlusion. Functional neuroscores and magnetic resonance imaging endpoints (infarct volumes, blood-brain barrier integrity, phagocytic activity assessed by iron oxide uptake) were longitudinally monitored for 2 weeks. This cell-based treatment did not significantly improve any outcome measure compared with vehicle, suggesting that this strategy is not relevant to stroke therapy.