Despite advances in acute care, ischemic stroke remains a major cause of long-term disability. Approaches targeting both neuronal and glial responses are needed to enhance recovery and improve long-term outcome. The complement C3a receptor (C3aR) is a regulator of inflammation with roles in neurodevelopment, neural plasticity, and neurodegeneration. Using mice lacking C3aR (C3aR-/-) and mice overexpressing C3a in the brain, we uncovered 2 opposing effects of C3aR signaling on functional recovery after ischemic stroke: inhibition in the acute phase and facilitation in the later phase. Peri-infarct astrocyte reactivity was increased and density of microglia reduced in C3aR-/- mice; C3a overexpression led to the opposite effects. Pharmacological treatment of wild-type mice with intranasal C3a starting 7 days after stroke accelerated recovery of motor function and attenuated astrocyte reactivity without enhancing microgliosis. C3a treatment stimulated global white matter reorganization, increased peri-infarct structural connectivity, and upregulated Igf1 and Thbs4 in the peri-infarct cortex. Thus, C3a treatment from day 7 after stroke exerts positive effects on astrocytes and neuronal connectivity while avoiding the deleterious consequences of C3aR signaling during the acute phase. Intranasal administration of C3aR agonists within a convenient time window holds translational promise to improve outcome after ischemic stroke.

• Keywords
• Complement, Neuroscience, Stroke,
• MeSH
• Astrocytes MeSH
• Stroke * drug therapy   genetics   MeSH
• Infarction MeSH
• Ischemic Stroke * MeSH
• Complement C3a genetics   MeSH
• Mice MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Complement C3a MeSH

The role of complement has been demonstrated in experimental models of neuromyelitis optica (NMO), however, only few studies have analysed complement components longitudinally in NMO patients. We measured serum or plasma concentrations of anti-C1q antibodies and complement split products C3a and C4a and soluble C5b-9 in patients with NMO, multiple sclerosis and healthy controls. NMO patients had higher levels of C3a and anti-C1q antibodies than healthy controls. C3a levels correlated with disease activity, neurological disability and aquaporin-4 IgG in NMO patients suggesting a role of the alternative pathway of complement in the pathogenesis of NMO and supporting the strategy of therapeutic complement inhibition.

• Keywords
• Aquaporin-4 IgG, C1q antibodies, Complement, Neuromyelitis optica,
• MeSH
• Complement Activation immunology   MeSH
• Aquaporin 4 immunology   MeSH
• Autoantibodies blood   immunology   MeSH
• Adult MeSH
• Immunoglobulin G blood   immunology   MeSH
• Complement C1q immunology   metabolism   MeSH
• Complement C3a immunology   metabolism   MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Follow-Up Studies MeSH
• Neuromyelitis Optica immunology   MeSH
• Prospective Studies MeSH
• Multiple Sclerosis, Relapsing-Remitting immunology   MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Aquaporin 4 MeSH
• AQP4 protein, human MeSH Browser
• Autoantibodies MeSH
• Immunoglobulin G MeSH
• Complement C1q MeSH
• Complement C3a MeSH

Multiple hormones and enzymes participate in the lipid storage. One of them is acylation stimulating protein. Acylation stimulating protein is produced predominantly by adipocytes. After the binding on specific receptor at the surface of adipocytes, acylation stimulating protein leads to enhancement of triglyceride synthesis. This process is mediated by protein-kinase C. Concurrently, glucose transporters move from the cytoplasm to the adipocyte surface. Higher glucose disposal leads to a sufficient substrate availability for triglyceride synthesis. Acylation stimulating protein also stimulates pancreatic insulin secretion. Total acylation stimulating protein level in plasma is related to the adipose tissue mass and it positively correlates with many anthropometric parameters and with serum insulin level. In acylation stimulating protein deficient mice, resistance to the obesity development after a high fat diet was observed. Adipose tissue mass is lower in the acylation stimulating protein deficient mice and higher insulin sensitivity was shown in acylation stimulating protein deficient mice compared to a wild type mice. Acylation stimulating protein pathway may have an important role in the obesity development.

• MeSH
• Complement C3a physiology   MeSH
• Fatty Acids, Nonesterified metabolism   MeSH
• Humans MeSH
• Lipogenesis MeSH
• Adipose Tissue metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• English Abstract MeSH
• Journal Article MeSH
• Review MeSH
• Names of Substances
• complement C3a, des-Arg-(77)- MeSH Browser
• Complement C3a MeSH
• Fatty Acids, Nonesterified MeSH