Journal ArticleDOI
Neuronal protection in stroke by an sLex-glycosylated complement inhibitory protein.
Judy Huang,Louis J. Kim,Richard A. Mealey,Henry C. Marsh,Yuan Zhang,Andrea J. Tenner,E. Sander Connolly,David J. Pinsky +7 more
TLDR
A hybrid molecule was used to simultaneously inhibit both complement activation and selectin-mediated adhesion in ischemic neurons and C1q-expressing neurons, inhibited neutrophil and platelet accumulation, and reduced cerebral infarct volumes.Abstract:
Glycoprotein adhesion receptors such as selectins contribute to tissue injury in stroke. Ischemic neurons strongly expressed C1q, which may target them for complement-mediated attack or C1qRp-mediated clearance. A hybrid molecule was used to simultaneously inhibit both complement activation and selectin-mediated adhesion. The extracellular domain of soluble complement receptor-1 (sCR1) was sialyl Lewis x glycosylated (sCR1sLex) to inhibit complement activation and endothelial-platelet-leukocyte interactions. sCR1 and sCR1sLex colocalized to ischemic cerebral microvessels and C1q-expressing neurons, inhibited neutrophil and platelet accumulation, and reduced cerebral infarct volumes. Additional benefit was conferred by sialyl Lewis x glycosylation of the unmodified parent sCR1 molecule.read more
Citations
More filters
Journal ArticleDOI
Mechanisms, challenges and opportunities in stroke
TL;DR: This new research focus addresses an important need in stroke research, provides challenges and opportunities that can be used to therapeutic advantage and is focused on how blood vessels and brain cells communicate with each other.
Journal ArticleDOI
The inflammatory response in stroke.
TL;DR: The role of specific cell types including leukocytes, endothelium, glia, microglia, the extracellular matrix and neurons, and mediators produced by inflammatory cells such as cytokines, chemokines, reactive oxygen species and arachidonic acid metabolites are reviewed.
Journal ArticleDOI
Gene-expression profile of the ageing brain in mice.
TL;DR: Caloric restriction, which retards the ageing process in mammals, selectively attenuated the age-associated induction of genes encoding inflammatory and stress responses, which resulted in a gene-expression profile indicative of an inflammatory response, oxidative stress and reduced neurotrophic support in both brain regions.
Journal ArticleDOI
Role of C5a in inflammatory responses
Ren Feng Guo,Peter A. Ward +1 more
TL;DR: Accumulating data suggest that C5a provides a vital bridge between innate and adaptive immune functions, extending the roles of C5o in inflammation.
References
More filters
Journal ArticleDOI
A Semiautomated Method for Measuring Brain Infarct Volume
Raymond A. Swanson,Raymond A. Swanson,Matthew T. Morton,George Tsao-Wu,George Tsao-Wu,Robert A. Savalos,Robert A. Savalos,Charisse Davidson,Charisse Davidson,Frank R. Sharp,Frank R. Sharp +10 more
TL;DR: An accurate, reproducible method for determining the infarct volumes of gray matter structures is presented for use with presently available image analysis systems, which minimizes the error that is introduced by edema, which distorts and enlarges theinfarcted tissue and surrounding white matter.
Journal ArticleDOI
Soluble human complement receptor type 1: in vivo inhibitor of complement suppressing post-ischemic myocardial inflammation and necrosis
Harlan F. Weisman,Thomas J. Bartow,Michelle K. Leppo,Henry C. Marsh,Gerald R. Carson,Michael F. Concino,Michael P. Boyle,Kenneth H. Roux,Myron L. Weisfeldt,Douglas T. Fearon +9 more
TL;DR: The sCR1 had complement inhibitory and anti-inflammatory activities in a rat model of reperfusion injury of ischemic myocardium, reducing myocardial infarction size by 44 percent and is identified as a potential agent for the suppression of complement-dependent tissue injury in autoimmune and inflammatory diseases.
Journal ArticleDOI
Intravenous Tissue Plasminogen Activator for Acute Ischemic Stroke Feasibility, Safety, and Efficacy in the First Year of Clinical Practice
David Chiu,Derk Krieger,Carlos Villar-Cordova,Scott E. Kasner,Lewis B. Morgenstern,Patti Bratina,Frank M. Yatsu,James C. Grotta +7 more
TL;DR: When treatment guidelines are carefully followed in an urban hospital setting, intravenous t-PA for acute ischemic stroke is feasible and shows safety and efficacy comparable to the results of the NINDS study.
Journal Article
Purification and radiolabeling of human C1q.
TL;DR: A new procedure for isolating human C1q from serum or plasma, that is highly selective, rapid and involves minimal handling, yields fully active, immunoglobulin-free unaggregated C1Q.
Journal Article
Soluble complement receptor type 1 ameliorates the local and remote organ injury after intestinal ischemia-reperfusion in the rat.
TL;DR: In this model, C is a major mediator of intestinal injury and extraintestinal injury by inhibiting C activation in a rat model of mesenteric arterial occlusion and sCR1 reduced the release of factor VIII-related Ag, 5-day mortality, and C hemolytic activity.