Novel TNF receptor-1 inhibitors identified as potential therapeutic candidates for traumatic brain injury.

Background: Traumatic brain injury (TBI) begins with the application of mechanical force to the head or brain, which initiates systemic and cellular processes that are hallmarks of the disease. The pathological cascade of secondary injury processes, including inflammation, can exacerbate brain injury-induced morbidities and thus represents a plausible target for pharmaceutical therapies. We have pioneered research on post-traumatic sleep, identifying that injury-induced sleep lasting for 6 h in brain-injured mice coincides with increased cortical levels of inflammatory cytokines, including tumor necrosis factor (TNF).

TGF-beta driven lung fibrosis is macrophage dependent and blocked by Serum amyloid P.

The pleiotropic growth factor TGFβ(1) promotes many of the pathogenic mechanisms observed in lung fibrosis and airway remodeling, such as aberrant extracellular matrix deposition due to both fibroblast activation and fibroblast to myofibroblast differentiation. Serum amyloid P (SAP), a member of the pentraxin family of proteins inhibits bleomycin-induced lung fibrosis through an inhibition of pulmonary fibrocyte and pro-fibrotic alternative (M2) macrophage accumulation. It is unknown if SAP has effects downstream of TGFβ(1), a major mediator of pulmonary fibrosis.

Serum amyloid P ameliorates radiation-induced oral mucositis and fibrosis.

Purpose: To evaluate the effect of the anti-fibrotic protein serum amyloid P (SAP) on radiation-induced oral mucositis (OM) and fibrosis in a hamster cheek-pouch model.

Experimental Design: Hamsters received a single dose of radiation (40 Gy) to the left everted cheek pouch to induce significant OM. The protective therapeutic potential of SAP was evaluated using varying dosing regimens.

Serum amyloid P therapeutically attenuates murine bleomycin-induced pulmonary fibrosis via its effects on macrophages.

Macrophages promote tissue remodeling but few mechanisms exist to modulate their activity during tissue fibrosis. Serum amyloid P (SAP), a member of the pentraxin family of proteins, signals through Fcgamma receptors which are known to affect macrophage activation. We determined that IPF/UIP patients have increased protein levels of several alternatively activated pro-fibrotic (M2) macrophage-associated proteins in the lung and monocytes from these patients show skewing towards an M2 macrophage phenotype.

Ventriculo-lumbar perfusion in acute ischemic stroke.

Introduction: Effective treatment for severe ischemic stroke continues to be largely an unmet medical need. Using a nonvascular (paravascular cerebrospinal fluid) pathway to provide oxygen and nutrients to ischemic tissues may be a means of treating this disease. The primary objective of this study was to evaluate the safety and technical feasibility of ventriculo-lumbar perfusion with the oxygenated fluorocarbon nutrient emulsion (OFNE) perfusion system in the treatment of patients with severe hemispheric cerebral ischemia.