**Author details**

myelin. Recent studies have used a biophysical approach to identify signals that promote the formation of myelin on artificial substrates. When grown in the presence of inert fibers of the appropriate dimensions, oligodendrocytes will begin to enwrap them as if they were immature axons. Molecules that enhance that process are considered strong candidate to promote remyelination in the CNS, and molecules including Clemastine an anti-histamine drug have

While the reductionist approaches provide important insights into isolated cellular responses of the oligodendrocyte lineage, they lack any physiological setting. As a result, it is unclear whether signals that modulate oligodendrocyte maturation in isolation will promote myelin repair in the developing or diseased CNS. One model to address this concern is the use of slice cultures. Slices of the CNS grown on the air/medium interface develop robust myelination. The most successful slices are those derived from cerebellum and coronal sections through the corpus callosum. Treatment of such slices with LPC results in rapid demyelination and allows for analysis of drug-induced repair in an efficient and physiological environment. In most studies, multiple different models are used to determine the efficacy individual com-

There is a broad range of animal models that address distinct aspects of multiple sclerosis and other demyelinating diseases. Each of the models has specific strengths and weaknesses in furthering our understanding of the pathogenic processes that mediate demyelination and in identifying new opportunities for the effective promotion of myelin repair. EAE models have led to the development of many therapeutic targets aimed at halting disease progression. More recently, other models such as those targeting oligodendrocyte cell death have been instrumental in fine-tuning our understanding of the pathology of demyelination/ remyelination in MS and other similar diseases. Each of the model systems discussed in this review deserves particular credit, as it has helped solve a different piece of the puzzle. For example, while EAE models have unraveled many of the immunological bases of the CNS demyelination, particularly the role of T cells in MS, the use of glial toxins such as LPC or ethidium bromide has emerged as extremely useful in reshaping our understanding of the environmental and cell-based mechanisms of remyelination, and the models of oligodendrocyte death provide insights into factors driving the pathology. It seems likely that new models will be forthcoming that more effectively address the role of cells other than those of the immune and oligodendrocyte lineage. Understanding the role of microglia and astrocytes, as well as further clarity around the mechanism of vascular components in disease progression,

will allow new therapeutic avenues to be developed in future studies.

This work was supported by NIH grant NS 30800 to R.H. Miller.

been identified in similar assays.

140 Neuroplasticity - Insights of Neural Reorganization

pounds to promote remyelination.

**3. Conclusions and comments**

**Acknowledgements**

Robert H. Miller<sup>1</sup> \*, Molly Karl1 , Reshmi Tognatta<sup>2</sup> , Ahdeah Pajoohesh-Ganji<sup>1</sup> and Mohammad Abu-Rub<sup>1</sup>

\*Address all correspondence to: rhm3@gwu.edu

1 School of Medicine and Health Sciences, George Washington University, Washington, DC, USA

2 Gladstone Institute, San Francisco, CA, USA
