alpha-Neup5Ac-(2--3)-beta-D-Galp-(1--4)-[alpha-L-Fucp-(1--3)]-D-GlcpNAc and Cerebrovascular-Disorders

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.

Topics: Animals; Blood Platelets; Cell Adhesion; Cerebral Cortex; Cerebral Infarction; Cerebrovascular Circulation; Cerebrovascular Disorders; Complement Activation; Complement C1q; Glycosylation; Humans; Ischemic Attack, Transient; Leukocytes; Mice; Neurons; Neuroprotective Agents; Neutrophils; Oligosaccharides; Platelet Adhesiveness; Receptors, Complement; Reperfusion Injury; Selectins; Sialyl Lewis X Antigen; Time Factors