Nature Medicine

When the blood supply to a certain part of the brain is cut off-an event known as ischemic stroke-the neurons beyond the blocked blood supply are destroyed and if the condition is not treated within hours by clot-dissolving drugs, large areas of the brain are damaged irreparably.

One way in which neurons deprived of oxygen and blood are damaged is by a dramatic rise in the levels of calcium within the cells. Efforts are being made to develop medicines that prevent this calcium-induced damage, and scientists from Bristol Myers Squibb have developed a new class of drugs that may be effective against stroke by acting to prevent this calcium overload of cells.

Using a rat model of stroke, Valentin Gribkoff and colleagues tested the ability of BMS-204352 to protect against neuronal damage. Two hours after blocking a major artery to the brain, rats that were injected with BMS-204352 suffered significantly less brain damage than control animals. The compound is now undergoing safety tests in humans.

BMS-204352 works by opening what are known as large-conductance, calcium-activated potassium channels in the brain. These channels redress the balance of ions within neurons by ejecting potassium from cells which, in turn, prevents the further entry of calcium.

Nature Medicine

One of the most controversial issues in research today revolves around the potential medical use of stem cells derived from embryos. Britain has become the first country to approve research into this technique. To back up the ethical arguments against the use of embryonic tissue, there is also a scientific basis for believing that stem cells from adults will be just as effective as those from embryos. The case 'For and Against' human embryonic stem cells is presented in two Commentaries in the April issue of Nature Medicine written by prominent researchers working in the United Kingdom.

In addition, a paper in the same issue reports that stem cells taken from adult bone marrow could form the basis of a cure for heart failure.

Although many people survive a heart attack, it is after the attack when damage to the heart muscle becomes life threatening. The affected area of the heart undergoes a process of 'remodeling' in which the heart cells grow abnormally large, the area is infiltrated by new blood vessels attempting to compensate for the enlarging cell mass and tissue is replaced by fibrous scar tissue.

Replacing this diseased tissue with new cells would solve the problem. Silviu Itescu and colleagues at Columbia-Presbyterian Medical Center selected cells from adult bone marrow with the characteristics of embryonic angioblasts- cells that give rise to the endothelial lining of blood vessels. They injected these cells into the tails of rats that had experienced a heart attack and found that the cells caused new blood vessels to grow within the damaged part of the heart. Because the blood supply was improved to this area, fewer of the heart cells died compared with non-treated rats. The treatment also caused a reduction in collagen deposits and scar formation and lead to an overall improvement in cardiac function.

If the technique extends to humans, it has the potential to significantly reduce morbidity and mortality associated with heart attack. Nadia Rosenthal and Lana Tsao of Massachusetts General Hospital discuss the work in an accompanying News & Views article.

Nature Medicine

Vascular endothelial growth factor (VEGF) and similar molecules are currently under investigation as potential treatments for heart disease because of their amazing ability to stimulate the growth of new blood vessels. However, a controversial report in the April issue of Nature Medicine suggests that such molecules have a downside-they cause atherosclerosis.

Michael Dake and colleagues from Stanford University Medical Center tested the ability of VEGF to cause the growth of atherosclerotic plaques in mice and rabbits that are prone to developing the condition. They found that low doses of the molecule significantly increased the size of plaques in major arteries in the animals. If the same thing happens in humans, it may be that people that are predisposed to atherosclerosis should be excluded from treatment with VEGF drugs.

Anthony Ware of Albert Einstein College of Medicine discusses the clinical implications of the study in an accompanying News & Views article. He points out that among the 800 or so patients have received agents such as VEGF so far, there has been no reported increase in the number of cardiac events, suggesting that if VEGF promotes atherosclerosis, it does so at a level that does not worsen clinical outcome.

Nature Medicine

The present consensus is that the most likely route of infection of bovine spongiform encephalopathy (BSE) and new-variant Creutzfeldt-Jakob disease (vCJD) has been through the food chain-eating products contaminated with abnormal prion protein. The infectious prion then replicates in lymph tissues before moving through the nerves to the spinal cord or brain stem. Thus, anything that could impair replication of abnormal prions in the lymph nodes would delay the onset of clinical signs of this type of disease. Two papers in the April issue of Nature Medicine report on a way that this could be achieved.

Neil Mabbott and colleagues at the Neuropathogenesis Unit in Edinburgh, Scotland, and Adriano Aguzzi's team at University of Zurich have discovered that depleting components of one part of the immune system called the complement system significantly delays the onset of disease symptoms in mice injected with scrapie.

The scientists treated mice with cobra venom factor (CVF), which is known to deplete levels of a complement molecule called C3 for five days. They then injected mice either intraperitoneally (i.p.) or intracerebrally with the infectious scrapie agent. For mice that had been infected i.p., the researchers discovered that those treated with CVF took longer to develop clinical symptoms of the disease than non-treated animals and that the early accumulation of abnormal prions in the spleen was reduced. The course of disease progression was the same in all animals that were infected by durect injection into the brain.

Franco Cardone and Maurizio Pocchiari from the Istituto Superiore di Sante in Italy discuss the experiments in an accompanying News & Views article.