Room: ePoster Forums
Purpose: Irradiation of the central nervous system (CNS) with arrays of thin (~0.3 mm), parallel planes of x-rays, called microbeams or minibeams, can produce substantial remyelination. The main feature of x-ray microbeams is their extraordinary tissue-sparing effect that has been observed over the past 25 years mostly by synchrotron-generated x-ray microbeams.
Methods: Rats were irradiated in their spinal cord transaxially with a single 0.27-mm thick synchrotron-generated x-ray microbeam at a 750-Gy dose.
Results: Rats exhibited nearly full demyelination in two weeksâ€”seen through immunostaining with myelin-basic proteins (MBP)â€”followed by nearly full remyelination in three months. The axons in the white matter were mostly spared, as seen from neurofilament staining, and the rats walked quite normally during the demyelination period. The observed remyelination was attributed to the proliferation of the oligodendrocyte precursor cells (OPCs), also called progenitor glial cells, soon after the irradiation. This proliferation was caused by the loss of the â€œcontact inhibitionâ€? of OPCs, which is in place when they are surrounded by myelin. In the above example, the proliferating cells then migrated into the 0.27-mm-wide depletion of cells, differentiated, produced mature oligodendrocytes, and produced myelin.
Conclusion: The observed effect has the potential to become the basis for a clinical remyelination method with a significant power to help patients debilitated by demyelinated lesions, such as those of multiple sclerosis (MS). We note that although MS is an autoimmune disease, it often leads to the production of lingering lesions of either demyelinated or poorly myelinated tissue. X-ray microbeam irradiations of such lesions can help those conditions by partially or fully remyelinating the lesion. Furthermore, regenerative properties aside, this new method of inducing demyelination with a precise location and timing without breaching the CNS is valuable in and of itself as a significant tool for the community to study myelin repair.
Funding Support, Disclosures, and Conflict of Interest: This study was funded by the NIH NINDS grant NS43231 and the Office of Biological and Environmental Research, U.S. Department of Energy (DOE). The research was carried out at the NSLS, which is supported by the U.S. DOE, Division of Materials Sciences and Division of Chemical Sciences, under Contract DE-AC02-98CH10886.