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Repeated X-Ray Microbeam Irradiation of the Rat Spinal Cord Contusion Injury Produces Substantial Hind-Leg Functional Recovery

JR Nassimi1*, DC Heaney1 , RF Cattell1 , KN Hirsch1 , SS Alam1 , S Siddiqui1 , NN Fatemi2 , JE Davis1 , CR Messina1 , J Rooney1 , T Zimmerman1 , ME Schweitzer1 , L Bangiyev1 , FA Dilmanian1 , (1) Stony Brook University Hospital, Stony Brook, NY, (2) City of Hope National Comprehensive Cancer Center, Duarte, CA


(Wednesday, 7/17/2019) 10:30 AM - 11:00 AM

Room: Exhibit Hall | Forum 3

Purpose: Spinal cord injury (SCI), specifically contusion injury, is a major health problem with no current effective treatment. Studies with rats have shown that irradiation of contusion injury with conventional x-rays in the first few days post-injury improves their hind-leg function. However, such irradiations at the doses used can produce late radiation effects if used clinically. This long-term radiation damage can be mitigated by using a collimator to segment the solid beam into arrays of thin (~0.3 mm), parallel planes of x rays, called x-ray microbeams. The tissue-sparing effect of microbeams (≤0.3 mm) and their thicker counterpart, minibeams (0.3-0.7 mm), has been demonstrated by experiments with synchrotron x rays and recently by orthovoltage x rays.

Methods: Spinal cord contusion injury was induced in rats at T9-T10 by a 25-mm rod drop using the NYU impactor. The rat spinal cords were subsequently irradiated with 100-kVp x-ray microbeams at an in-beam incident dose of 52 Gy on each of days 2, 5, and 12 post-injury. To determine the effects of the radiation on the contusion injury, the rats were scored using the BBB scoring method, which utilizes a 0-21 scale, with 0 being complete paralysis and 21 being full mobility

Results: Seven months post-injury, all of the irradiated rats presented BBB scores of 14-18, while the average score of the non-irradiated controls was 10.5. This functional improvement has been tentatively attributed to the ablation of astrocytes and infiltrating immune cells, including macrophages, which are peaked in their population around the chosen irradiation time-points.

Conclusion: These results suggest that minibeam irradiation could become a new treatment method of SCI, using either high-power orthovoltage x-ray machines or compact synchrotrons. Future research will involve producing a larger sample size to gain adequate significant data to propel the research towards early stage human clinical trials.


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