Targeting Different Monocyte/Macrophage Subsets Has No Impact on Outcome in Experimental Stroke.

Schmidt A, Strecker JK, Hucke S, Bruckmann NM, Herold M, Mack M, Diederich K, Schäbitz WR, Wiendl H, Klotz L, Minnerup J.

Zusammenfassung

Background and Purpose: The inflammatory response is considered as an important therapeutic target following ischemic stroke. But, in spite of a huge number of immigrating monocytes/macrophages, the functional relevance of different monocyte/macrophage subsets in acute ischemic stroke has been scarcely investigated and long-term effects of monocytes/macrophages on the neural recovery beyond the acute phase of stroke have not been elaborated yet.Methods: To assess short-term effects of monocytes/macrophages in acute ischemic stroke, 158 adult C57BL/6 mice underwent transient middle cerebral artery occlusion (MCAO) and received either clodronate liposomes for unselective macrophage depletion, MC-21-antibody for selective depletion of proinflammatory Ly-6Chigh monocytes, proinflammatory (M1-) or antiinflammatory (M2-) macrophages. In addition, we investigated long-term effects of MC-21-antibody administration and M2-macrophage transplantation on the neural recovery following photothrombotic stroke. Menzies Neuroscore, rotarod, adhesive tape removal and foot fault tests were employed to analyze functional outcomes, infarct volumes were determined and immunohistochemical analyses were performed to characterize the postischemic inflammatory reaction. Monocyte/macrophage depletion was verified by flow cytometry.Results: Selective and unselective monocyte/macrophage depletion and M1- or M2- macrophage transplantation did not influence neurological and histological outcomes in the acute phase after MCAO (p>0.05). Beyond, selective depletion of Ly-6Chigh monocytes and transplantation of M2-macrophages did not have an impact on the neural recovery after photothrombotic stroke (p>0.05).Conclusions: Selective and unselective targeting of different monocyte/macrophage subsets did not influence functional and histological outcomes in two models of ischemic stroke. We assume that other immune cells are able to equalize monocyte/macrophage functions following ischemic stroke.