Cyclosporin-A treatment attenuates delayed cytoskeletal alterations and secondary axotomy following mild axonal stretch injury.

Following central nervous system trauma, diffuse axonal injury and secondary axotomy result from a cascade of cellular alterations including cytoskeletal and mitochondrial disruption. We have examined the link between intracellular changes following mild/moderate axonal stretch injury and secondary axotomy in rat cortical neurons cultured to relative maturity (21 days in vitro). Axon bundles were transiently stretched to a strain level between 103% and 106% using controlled pressurized fluid. Double-immunohistochemical analysis of neurofilaments, neuronal spectrin, alpha-internexin, cytochrome-c, and ubiquitin was conducted at 24-, 48-, 72-, and 96-h postinjury. Stretch injury resulted in delayed cytoskeletal damage, maximal at 48-h postinjury. Accumulation of cytochrome-c and ubiquitin was also evident at 48 h following injury and colocalized to axonal regions of cytoskeletal disruption. Pretreatment of cultures with cyclosporin-A, an inhibitor of calcineurin and the mitochondrial membrane transitional pore, reduced the degree of cytoskeletal damage in stretch-injured axonal bundles. At 48-h postinjury, 20% of untreated cultures demonstrated secondary axotomy, whereas cyclosporin A-treated axon bundles remained intact. By 72-h postinjury, 50% of control preparations and 7% of cyclosporin A-treated axonal bundles had progressed to secondary axotomy, respectively. Statistical analyses demonstrated a significant (p < 0.05) reduction in secondary axotomy between treated and untreated cultures. In summary, these results suggest that cyclosporin-A reduces progressive cytoskeletal damage and secondary axotomy following transient axonal stretch injury in vitro.

Cardiac events after myocardial infarction: possible effect of relaxation therapy.

Comprehensive cardiac rehabilitation aims primarily at improving quality of life, but an effect on morbidity and mortality may also be expected, especially when changes in behaviour and life-style are induced. The value of relaxation therapy and exercise training in post myocardial infarction (MI) patients was investigated. A group of 90 post MI patients were randomly assigned to either exercise training plus individual relaxation and breathing therapy (treatment A), or exercise training only (treatment B). The occurrence of cardiac events, consisting of cardiac death and of readmission to hospital for unstable angina pectoris, coronary artery bypass grafting (CABG) or recurrent infarction, differed significantly for the two treatment groups in the 2-3 years after infarction. Seven out of 42 patients in treatment group A (17%) experienced a cardiac event, in contrast to 17 out of 46 (37%) patients in treatment group B, (P = 0.05, two-tailed). The results suggest that a combination of a behavioural treatment such as relaxation therapy with exercise training is more favourable for the long-term outcome after myocardial infarction than is exercise training alone.