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Open Access Highly Accessed Research article

Solulin reduces infarct volume and regulates gene-expression in transient middle cerebral artery occlusion in rats

Yu-Mi Ryang12*, Jon Dang3, Markus Kipp3, Karl-Uwe Petersen4, Astrid V Fahlenkamp35, Jens Gempt1, Dominik Wesp6, Rolf Rossaint5, Cordian Beyer3 and Mark Coburn5

Author affiliations

1 Department of Neurosurgery, Klinikum rechts der Isar, Hospital of the Technical University Munich, Ismaningerstr. 22, 81675 Munich, Germany

2 Department of Neurosurgery, University Hospital of the RWTH Aachen, Pauwelsstraße 30, 52074 Aachen, Germany

3 Institute of Neuroanatomy, Faculty of Medicine, RWTH Aachen University, Wendlingweg 2, 52074 Aachen, Germany

4 PAION Deutschland GmbH Aachen, Martinstr. 10-12, 52062 Aachen, Germany

5 Department of Anesthesiology, University Hospital of the RWTH Aachen, Pauwelsstraße 30, 52074 Aachen, Germany

6 Department of Neurosurgery, Georg-August-University Hospital, Robert-Koch-Straße 40, 37075 Göttingen, Germany

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Citation and License

BMC Neuroscience 2011, 12:113  doi:10.1186/1471-2202-12-113

Published: 14 November 2011

Abstract

Background

Thrombolysis after acute ischemic stroke has only proven to be beneficial in a subset of patients. The soluble recombinant analogue of human thrombomodulin, Solulin, was studied in an in vivo rat model of acute ischemic stroke.

Methods

Male SD rats were subjected to 2 hrs of transient middle cerebral artery occlusion (tMCAO). Rats treated with Solulin intravenously shortly before reperfusion were compared to rats receiving normal saline i.v. with respect to infarct volumes, neurological deficits and mortality. Gene expression of IL-6, IL-1β, TNF-α, MMP-9, CD11B and GFAP were semiquantitatively analyzed by rtPCR of the penumbra.

Results

24 hrs after reperfusion, rats were neurologically tested, euthanized and infarct volumes determined. Solulin significantly reduced mean total (p = 0.001), cortical (p = 0.002), and basal ganglia (p = 0.036) infarct volumes. Hippocampal infarct volumes (p = 0.191) were not significantly affected. Solulin significantly downregulated the expression of IL-1β (79%; p < 0.001), TNF-α (59%; p = 0.001), IL-6 (47%; p = 0.04), and CD11B (49%; p = 0.001) in the infarcted cortex compared to controls.

Conclusions

Solulin reduced mean total, cortical and basal ganglia infarct volumes and regulated a subset of cytokines and proteases after tMCAO suggesting the potency of this compound for therapeutic interventions.