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5 December 2012 X-Ray Microbeam Irradiation of the Contusion-Injured Rat Spinal Cord Temporarily Improves Hind-Limb Function
F. Avraham Dilmanian, Arthur L. Jenkins, John A. Olschowka, Zhong Zhong, Jane Y. Park, Nicolle R. Desnoyers, Stanislaw Sobotka, Giovanna R. Fois, Catherine R. Messina, Marjorie Morales, Sean D. Hurley, LeeAnn Trojanczyk, Saffa Ahmad, Neda Shahrabi, Patricia K. Coyle, Allen G. Meek, M. Kerry O'Banion
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Abstract

Spinal cord injury is a devastating condition with no effective treatment. The physiological processes that impede recovery include potentially detrimental immune responses and the production of reactive astrocytes. Previous work suggested that radiation treatment might be beneficial in spinal cord injury, although the method carries risk of radiation-induced damage. To overcome this obstacle we used arrays of parallel, synchrotron-generated X-ray microbeams (230 μm with 150 μm gaps between them) to irradiate an established model of rat spinal cord contusion injury. This technique is known to have a remarkable sparing effect in tissue, including the central nervous system. Injury was induced in adult female Long-Evans rats at the level of the thoracic vertebrae T9-T10 using 25 mm rod drop on an NYU Impactor. Microbeam irradiation was given to groups of 6–8 rats each, at either Day 10 (50 or 60 Gy in-beam entrance doses) or Day 14 (50, 60 or 70 Gy). The control group was comprised of two subgroups: one studied three months before the irradiation experiment (n = 9) and one at the time of the irradiations (n = 7). Hind-limb function was blindly scored with the Basso, Beattie and Bresnahan (BBB) rating scale on a nearly weekly basis. The scores for the rats irradiated at Day 14 post-injury, when using t test with 7-day data-averaging time bins, showed statistically significant improvement at 28–42 days post-injury (P < 0.038). H&E staining, tissue volume measurements and immunohistochemistry at day ∼110 post-injury did not reveal obvious differences between the irradiated and nonirradiated injured rats. The same microbeam irradiation of normal rats at 70 Gy in-beam entrance dose caused no behavioral deficits and no histological effects other than minor microglia activation at 110 days. Functional improvement in the 14-day irradiated group might be due to a reduction in populations of immune cells and/or reactive astrocytes, while the Day 10/Day 14 differences may indicate time-sensitive changes in these cells and their populations. With optimizations, including those of the irradiation time(s), microbeam pattern, dose, and perhaps concomitant treatments such as immunological intervention this method may ultimately reach clinical use.

F. Avraham Dilmanian, Arthur L. Jenkins, John A. Olschowka, Zhong Zhong, Jane Y. Park, Nicolle R. Desnoyers, Stanislaw Sobotka, Giovanna R. Fois, Catherine R. Messina, Marjorie Morales, Sean D. Hurley, LeeAnn Trojanczyk, Saffa Ahmad, Neda Shahrabi, Patricia K. Coyle, Allen G. Meek, and M. Kerry O'Banion "X-Ray Microbeam Irradiation of the Contusion-Injured Rat Spinal Cord Temporarily Improves Hind-Limb Function," Radiation Research 179(1), 76-88, (5 December 2012). https://doi.org/10.1667/RR2921.1
Received: 2 January 2012; Accepted: 1 July 2012; Published: 5 December 2012
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