NO donors exhibit anti-inflammatory properties by modulating inflammatory signatures and by regulating the life cycle of dendritic cells.

NO mediates a variety of physiologic processes and is considered an important intracellular messenger in different cellular systems. Because of its complex regulation and multiple molecular and cellular targets, NO provides both stimulatory and suppressive properties in the immune system. Dendritic cells (DCs) are considered the most potent APCs, whose regulation has important implications in the induction of an effective immune response.

Optimized "in vitro" culture conditions for human rheumatoid arthritis synovial fibroblasts.

The composition of synovial fluid in rheumatoid arthritis (RA) is complex and strongly influences the microenvironment of joints and it is an inseparable element of the disease. Currently, "in vitro" studies are performed on RA cells cultured in the presence of either recombinant proinflammatory cytokines-conditioned medium or medium alone. In this study, we evaluated the use of synovial fluid, derived from RA patients, as optimal culture condition to perform "in vitro" studies on RA synovial fibroblasts.

Recombinant C1 inhibitor in brain ischemic injury.

Objective: C1 inhibitor (C1-INH) is an endogenous inhibitor of complement and kinin systems. We have explored the efficacy and the therapeutic window of the recently available human recombinant (rh) C1-INH on ischemic brain injury and investigated its mechanism of action in comparison with that of plasma-derived (pd) C1-INH.

Methods: rhC1-INH was administered intravenously to C57Bl/6 mice undergoing transient or permanent ischemia, and its protective effects were evaluated by measuring infarct volume and neurodegeneration.

Neurosphere-derived cells exert a neuroprotective action by changing the ischemic microenvironment.

Background: Neurosphere-derived cells (NC), containing neural stem cells, various progenitors and more differentiated cells, were obtained from newborn C57/BL6 mice and infused in a murine model of focal ischemia with reperfusion to investigate if: 1) they decreased ischemic injury and restored brain function; 2) they induced changes in the environment in which they are infused; 3) changes in brain environment consequent to transient ischemia were relevant for NC action.

Methodology/principal Findings: NC were infused intracerebroventricularly 4 h or 7 d after 30 min middle cerebral artery occlusion. In ischemic mice receiving cells at 4 h, impairment of open field performance was significantly improved and neuronal loss significantly reduced 7-14 d after ischemia compared to controls and to ischemic mice receiving cells at 7 d.

Selective inhibition of plasma kallikrein protects brain from reperfusion injury.

We have studied the effect of DX-88, a selective recombinant inhibitor of human plasma kallikrein, in transient or permanent focal brain ischemia (with or without reperfusion, respectively) induced in C57BL/6 mice. Twenty-four hours after transient ischemia, DX-88 administered at the beginning of ischemia (pre) induced a dose-dependent reduction of ischemic volume that, at the dose of 30 microg/mouse, reached 49% of the volume of saline-treated mice. At the same dose, DX-88 was also able to reduce brain swelling to 32%.

C1-inhibitor protects against brain ischemia-reperfusion injury via inhibition of cell recruitment and inflammation.

Previous studies demonstrated that C1-inhibitor (C1-INH), a complement and contact-kinin systems inhibitor, is neuroprotective in cerebral ischemia. To investigate the mechanism of this action, we evaluated the expression of neurodegeneration and inflammation-related factors in mice subjected to 2-h ischemia and 2 or 46 h reperfusion. C1-INH significantly dampened the mRNA expression of the adhesion molecules P-selectin and ICAM-1 induced by the ischemic insult.

Peripheral treatment with enoxaparin, a low molecular weight heparin, reduces plaques and beta-amyloid accumulation in a mouse model of Alzheimer's disease.

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.

The powerful neuroprotective action of C1-inhibitor on brain ischemia-reperfusion injury does not require C1q.

C1-inhibitor (C1-INH) is a major regulator of the complement classical pathway. Besides this action, it may also 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.