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

<p>Abstract</p> <p>Background</p> <p>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 <it>in vivo </it>rat model of acute ischemic stroke.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p

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

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.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-1?, TNF-?, MMP-9, CD11B and GFAP were semiquantitatively analyzed by rtPCR of the penumbra.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-1? (79%; p<0.001), TNF-? (59%; p=0.001), IL-6 (47%; p=0.04), and CD11B (49%; p=0.001) in the infarcted cortex compared to controls.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

Neuroprotective effects of argon in an in vivo model of transient middle cerebral artery occlusion in rats.

The neuroprotective effects of the noble gas xenon are well known. Argon, in contrast to xenon, is abundant, inexpensive, and therefore widely applicable. In this study, we analyzed the possible neuroprotective role of argon in an in vivo rat model of acute focal cerebral ischemia.Controlled laboratory study.Academic research laboratory.Male adult Sprague-Dawley rats.Twenty-two rats underwent 2 hrs of transient middle cerebral artery occlusion using the endoluminal thread model. One hr after transient middle cerebral artery occlusion induction, spontaneously breathing rats received either 50 vol % argon/50 vol % O2 (argon group, n = 11) or 50 vol % N2/50 vol % O2 (control group, n = 11) for 1 hr through a face mask. Twenty-four hrs after reperfusion, rats were neurologically and behaviorally tested and euthanized. Rat brains were stained with 2,3,5-triphenyltetrazolium chloride and infarct volumes determined by planimetry.After 2 hrs of transient middle cerebral artery occlusion in the rat, we found in the argon group a significant reduction in the overall (p = .004) and after subdivision in the cortical (p = .007) and the basal ganglia (p = .02) infarct volumes. Argon treatment resulted in a significant improvement of the composite adverse outcome (p = .034). However, there was no advantage in acute survival 24 hrs after transient middle cerebral artery occlusion (p = .361).We were able to demonstrate argon's neuroprotective effects in an in vivo experimental rat model of acute focal cerebral ischemia. Animals breathing spontaneously 50 vol % argon 1 hr after induction of transient middle cerebral artery occlusion for 1 hr by face mask showed significantly reduced infarct volumes and composite adverse outcomes