Immunization with neurofilament light protein induces spastic paresis and axonal degeneration in Biozzi ABH mice.

Axonal damage is the major cause of irreversible neurologic disability in patients with multiple sclerosis. Although axonal damage correlates with antibodies against neurofilament light (NF-L) protein, a major component of the axonal cytoskeleton, the possible pathogenic role of autoimmunity to axonal antigens such as NF-L has so far been ignored. Here we show that Biozzi ABH mice immunized with NF-L protein develop neurologic disease characterized by spastic paresis and paralysis concomitant with axonal degeneration and inflammation primarily in the dorsal column of the spinal cord.

Optimizing engineered heart tissue for therapeutic applications as surrogate heart muscle.

Background: Cardiac tissue engineering aims at providing heart muscle for cardiac regeneration. Here, we hypothesized that engineered heart tissue (EHT) can be improved by using mixed heart cell populations, culture in defined serum-free and Matrigel-free conditions, and fusion of single-unit EHTs to multi-unit heart muscle surrogates.

Methods And Results: EHTs were constructed from native and cardiac myocyte enriched heart cell populations.

Endothelin-1 and isoprenaline co-stimulation causes contractile failure which is partially reversed by MEK inhibition.

Objective: The mitogen-activated kinase kinases (MEK)-extracellular signal-regulated kinases (ERK) signaling pathway is activated by agonists like catecholamines or endothelin-1 (ET-1) and has been implicated in cardiac pathology, such as the progression from cardiac hypertrophy to failure. The purpose of the present study, performed in an in vitro model of contractile failure, was to evaluate whether MEK inhibition prevents functional deterioration.

Methods And Results: Contractile dysfunction was induced in reconstituted rat heart tissue by concomitant treatment with ET-1 (10 nmol/l) and isoprenaline (ISO, 10 nmol/l) for 5 days.

3D engineered heart tissue for replacement therapy.

Myocardial infarction results in irreversible loss of cardiac myocytes and heart failure. Tissue or cell grafting offers the prospect of reintroducing contractile elements into impaired hearts. However, implanted cardiac myocytes remain physically and electrically isolated from the viable myocardium.