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

Schmidt, Antje and Strecker, Jan-Kolja and Hucke, Stephanie and Bruckmann, Nils-Martin and Herold, Martin and Mack, Matthias and Diederich, Kai and Schaebitz, Wolf-Ruediger and Wiendl, Heinz and Klotz, Luisa and Minnerup, Jens (2017) Targeting Different Monocyte/Macrophage Subsets Has No Impact on Outcome in Experimental Stroke. STROKE, 48 (4). pp. 1061-1069. ISSN 0039-2499, 1524-4628

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Abstract

Background and Purpose-Peripheral immune cell infiltration contributes to neural injury after ischemic stroke. However, in contrast to lymphocytes and neutrophils, the role of different monocyte/macrophage subsets remains to be clarified. Therefore, we evaluated the effects of selective and unselective monocyte/macrophage depletion and proinflammatory (M1-) and anti-inflammatory (M2-) macrophage transfer on the outcome after experimental cerebral ischemia. Methods-To assess short-term effects of monocytes/macrophages in acute ischemic stroke, mice underwent transient middle cerebral artery occlusion and received either clodronate liposomes for unselective macrophage depletion, MC-21-antibody for selective depletion of proinflammatory Ly-6C(high) monocytes, or proinflammatory (M1-) or anti-inflammatory (M2-) macrophage transfer. In addition, the impact of MC-21-antibody administration and M2-macrophage transfer on long-term neural recovery was investigated after photothrombotic stroke. Neurobehavioral tests were used to analyze functional outcomes, infarct volumes were determined, and immunohistochemical analyses were performed to characterize the postischemic inflammatory reaction. Results-Selective and unselective monocyte/macrophage depletion and M1- and M2-macrophage transfer did not influence tissue damage and neurobehavioral outcomes in the acute phase after middle cerebral artery occlusion. Beyond, selective depletion of Ly-6C(high) monocytes and M2-macrophage transfer did not have an impact on neural recovery after photothrombotic stroke. Conclusions-Targeting different monocyte/macrophage subsets has no impact on outcome after ischemic stroke in mice. Altogether, our study could not identify monocytes/macrophages as relevant therapeutic targets in acute ischemic stroke.

Item Type: Article
Uncontrolled Keywords: CEREBRAL-ARTERY OCCLUSION; ISCHEMIC BRAIN-INJURY; FUNCTIONAL RECOVERY; MICE; MACROPHAGES; ACTIVATION; MONOCYTES; CELLS; MECHANISMS; MICROGLIA; inflammation; macrophages; models; animal; monocytes; stroke
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Neurologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 14 Dec 2018 13:00
Last Modified: 25 Feb 2019 12:12
URI: https://pred.uni-regensburg.de/id/eprint/172

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