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Neurology Reviews.Com

Vol. 13, No. 5
May 2005


NEWS ROUNDUP:
NEW AND NOTEWORTHY INFORMATION

An updated consensus statement on assessment and management of concussions in athletes appeared in the March Clinical Journal of Sport Medicine. The report summarized the conclusions of a panel of sport medicine experts who met at the Second International Conference on Concussion in Sport, held in Prague. The statement highlighted the importance of physical examinations prior to sports participation to help target athletes with previous concussions. Also emphasized was the importance of classifying concussions according to the quality and timing of recovery after injury, rather than by previous injury grading scales. The statement included the Sideline Concussion Assessment Tool (SCAT), which provides information for non–health professionals on how to identify concussions, what steps to take, and the expected recovery. The opposite side of the SCAT features a pocket guide to on-the-scene assessment for use by physicians, trainers, or other health professionals.

Researchers have identified proteins that allow specific brain cells to “change channels,” ie, the ability to regulate calcium intake by swapping one kind of channel, or membrane opening, for another. As detailed in their study, which was published in the March 24 Neuron, the two proteins, PICK1 and NSF, replace channels that let calcium ions in with another kind of channel that keeps calcium out. Researchers have not determined the mechanism of this effect. According to the investigators, in people with amyotrophic lateral sclerosis, some muscle-controlling nerve cells die because an excess of glutamate binds to the cells’ AMPA receptors, allowing too much calcium inside the cells.

Functional diffusion map is effective as an MRI biomarker for predicting response to treatment in brain tumor patients, according to a study in the April 12 Proceedings of the National Academy of Sciences. Twenty patients with brain tumors were examined using standard and diffusion MRI before initiation of therapy. They were then given chemotherapy, radiation therapy, or both. After three weeks, additional images were acquired. According to the researchers, functional diffusion maps were found to predict patient response at three weeks from the start of treatment, with diffusion changes in any way—up or down—correlating with a positive outcome. “Using MRI tumor diffusion values to accurately predict the treatment response early on could allow some patients to switch to a more beneficial therapy and avoid the side effects of a prolonged and ineffective treatment,” said the researchers.

Investigators have been able to replicate symptoms of multiple system atrophy in mice, according to a report in the March 24 Neuron. The researchers found that the mice had accumulated filamentous human a-synuclein aggregates in oligodendrocytes, which were linked to the degeneration of oligodendrocytes and autophagocytosis of myelin. In addition, they found that “endogenous mouse a-synuclein also accumulated in normal and degenerating axons and axon terminals in association with oligodendroglia and neuron loss and slowly progressive motor impairments.” The researchers commented that, “the uniqueness of this disease is that unlike most of the neurodegenerative diseases, which affect neurons primarily and oligodendrocytes secondarily—this is the other way around.”

Investigators have shown that cholesterol is an important component of myelin membranes and that cholesterol availability in oligodendrocytes is a rate-limiting factor for brain maturation. According to the April Nature Neuroscience, a team of investigators created mice that lack the ability to synthesize cholesterol in the myelin-forming oligodendrocytes. They found that mutant mice displayed ataxia and tremor and had severely perturbed central nervous system myelination. The researchers said that myelination continued at a reduced rate for several months and that during this period, the cholesterol-deficient oligodendrocytes actively enriched cholesterol and assembled myelin with more than 70% of the cholesterol content of wild-type myelin.

Researchers have used RNA interference in transgenic mice to silence mutations in Cu/Zn superoxide dismutase (encoded by SOD1), one of the causes of familial amyotrophic lateral sclerosis. As detailed in the April issue of Nature Medicine, researchers delivered strands of RNA via lentiviral vector to mice that were bred to express the SOD1 gene. The investigators found that the onset and rate of progression of the disease in the treated mice were substantially delayed, and they observed significant improvement in neuromuscular function. The researchers said they “would not be surprised to see, in the next 10 years, this technology used for treating diseases of the nervous system, particularly diseases that involve toxic gain-of-function, such as inherited forms of Parkinson’s disease or Huntington’s disease.”

The cells that line the arteries are able to produce C-reactive protein, according to a study in the April American Journal of Pathology. Researchers have found that synthesis and secretion of C-reactive protein by cells in the atherosclerotic lesion could result in local concentrations of C-reactive protein far in excess of plasma concentrations and could contribute to proinflammatory, proatherogenic effects. “The C-reactive protein produced by endothelial cells cannot only act on the endothelial cells but also on macrophages and smooth muscle cells in the atheroma. This creates a vicious cycle, leading to plaque instability and rupture, and ultimately heart attacks and strokes,” they explained.

Researchers have determined that BG01V, a variant of the human embryonic stem cell (hESC) line BG01, may serve as a potential model for studies of dopaminergic neuronal differentiation of hESCs. As detailed in a report in Restorative Neurology and Neuroscience, the properties of BG01V cells were compared to those of normal BG01cells. The researchers determined that “BG01V cells expressed pluripotent ESC markers similar to BG01 cells, and retained the ability to differentiate into cell types characteristic of all three germ layers.” They also found that when co-cultured with the cell line PA6, BG01V cells were able to differentiate into dopaminergic cells. The investigators concluded that BG01V cells could be used as an alternative pluripotent hESC type for in vitro developmental studies.

New research has demonstrated that glycogen buildup in heart and skeletal muscle can be corrected in mice, using an AAV2 vector containing a muscle-specific promoter. As detailed in the March 10 online edition of Molecular Therapy, this finding suggests that such an approach should be considered as a potential gene therapy strategy for patients with Pompe’s disease. The investigators also highlighted the possibility of applying this approach in the treatment of other forms of muscular dystrophy. The findings support the results of a prior study, in which the investigators reported a similar outcome when they used liver-targeted gene therapy in a mouse model of Pompe’s disease.

NR

—Karen L. Spittler

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