Abstract
BackgroundThrombolysis 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.MethodsMale 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.Results24 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.ConclusionsSolulin 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.
Highlights
Thrombolysis after acute ischemic stroke has only proven to be beneficial in a subset of patients
We studied transcription levels of following factors: IL-6, IL-1b, TNF-a, Matrix metalloproteinases (MMP)-9, CD11B and glial fibrillary acidic protein (GFAP)
Edema corrected Infarct volumes Edema corrected total infarct volumes were assessed, as well as infarct volumes separated for cortex, basal ganglia and hippocampus
Summary
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. Stroke is a major cause of morbidity and mortality in the Western civilization. 60% of ischemic strokes are attributable to large-artery occlusion by thrombembolism. Complete absence of perfusion results in irreversible brain damage and neuronal loss in the stroke core. The surrounding penumbra contains functionally impaired, yet reversibly damaged neurons which are potentially salvageable. The goal in modern stroke therapy, is to protect the penumbra. The only approved drug for lysis therapy is recombinant tissue plasminogen activator (rtPA) which has shown significant benefit in patient outcome when given up to 4.5 hours of onset.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
