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

Yu Mi Ryang, Jon Dang, Markus Kipp, Karl Uwe Petersen, Astrid V. Fahlenkamp, Jens Gempt, Dominik Wesp, Rolf Rossaint, Cordian Beyer, Mark Coburn

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

29 Zitate (Scopus)

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.

OriginalspracheEnglisch
Aufsatznummer113
FachzeitschriftBMC Neuroscience
Jahrgang12
DOIs
PublikationsstatusVeröffentlicht - 14 Nov. 2011
Extern publiziertJa

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