We investigated the effect of long-term, peripheral treatment with enoxaparin, a low molecular weight heparin, in transgenic mice overexpressing human amyloid precursor protein(751). Enoxaparin (6 IU per mouse intraperitoneally, three times a week for 6 months) significantly lowered the number and the area occupied by cortical beta-amyloid deposits and the total beta-amyloid (1-40) cortical concentration. Immunocytochemical analysis of glial fibrillary acid protein-positive cells showed that enoxaparin markedly reduced the number of activated astrocytes surrounding beta-amyloid deposits. In vitro, the drug dose-dependently attenuated the toxic effect of beta-amyloid on neuronal cells. Enoxaparin dose-dependently reduced the ability of beta-amyloid to activate complement and contact systems, two powerful effectors of inflammatory response in AD brain. By reducing the beta-amyloid load and cytotoxicity and proinflammatory activity, enoxaparin offers promise as a tool for slowing the progression of Alzheimer's disease.

C1-inhibitor (C1-INH) is a major regulator of the complement classical pathway. Besides this action, it mayalso inhibit other related inflammatory systems. We have studied the effect of C1-INH in C57BL/6 mice with focal transient brain ischemia induced by 30 minutes of occlusion of the middle cerebral artery. C1-INH induced a dose-dependent reduction of ischemic volume that, with the dose of 15 U/mouse, reached 10.8% of the volume of saline-treated mice. Four days after ischemia the treated mice had significantly lower general and focal neurological deficit scores. Fluoro-Jade staining, a marker for neuronal degeneration, showed that C1-INH-treated mice had a lower number of degenerating cells. Leukocyte infiltration, as assessed by CD45 immunostaining, was also markedly decreased. We then investigated the response to ischemia in C1q ؊/؊ mice. There was a slight, nonsignificant decrease in infarct volume in C1q ؊/؊ mice (reduction to 72.3%) compared to wild types. Administration of C1-INH to these mice was still able to reduce the ischemic volume to 31.4%. The study shows that C1-INH has a strong neuroprotective effect on brain ischemia/reperfusion injury and that its action is independent from C1q-mediated activation of classical pathway. C1-inhibitor (C1-INH) is an acute phase protein belonging to the superfamily of serine protease inhibitors called serpins. It is the only known physiological inhibitor of C1s and C1r, the activated homologous serin proteases of the first component of the complement, thus playing an essential role as a regulator of complement classical pathway in blood and tissue.1 C1-INH is also one of the major inhibitors of plasma kallikrein and activated factor XII of the contact-kinin system. 2,3 Beside this essential role as regulator of the activation of complement classical pathway and of contact-kinin systems, there is evidence that C1-INH can also inhibit the complement lectin pathway proteases (MASP-1 and MASP-2), and the complement alternative pathway (C3b), plasmin, activated factor XI, plasminogen activator, and glandular kallikrein thus acting as a multifunctional regulator of the various kiningenerating cascade systems. 2-5Observations in patients receiving C1-INH as a replacement therapy for C1-INH deficiency, and studies in animal experimental models suggest that this molecule may be beneficial in clinical conditions in which activation of the complement and contact systems occurs.2,6 -9 A common feature to these systems is that on activation they give rise to biologically active peptides, including bradykinin (contact system) and anaphylatoxins (complement system) endowed with proinflammatory effects. Ischemia-reperfusion brain injury is accompanied by a marked inflammatory reaction that contributes to the evolution of tissue injury by several possible mechanisms including production of toxic mediators by activated glial and inflammatory cells and microvascular obstruction by neutrophils. 10,11 Complement is known to be activated in human stroke 12 as well as in experimental ...

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Systemic Lupus Erythematosus (SLE) is a chronic connective tissue disorder, found to be associated in up to 40% of cases to a secondary Antiphospholipid Syndrome (APS). SLE has a wide spectrum of clinical manifestations, ranging from mild to potentially lifethreating conditions. Patients presenting hematologic, renal, central nervous system or cardiac manifestations have been described as having a worse prognosis. Although SLE cardiac involvement alone is rarely responsible for patients' death, the mortality risk significantly increases when an APS is associated, making myocardial infarction and pulmonary embolism the main causes of morbidity and mortality in this group of patients. Here, we report on a case of fatal cardiac involvement in a male patient with a long-standing SLE history, whose post-mortem revealed a pulmonary thromboembolism likely due to a seronegative antiphospholipid syndrome.