Therapeutic Target for External Beam X-Irradiation in Experimental Spinal Cord Injury

OBJECTIVE: X-irradiation has been shown to be beneficial to recovery from spinal cord injury (SCI); however, the optimal therapeutic target has not been defined. Experiments were designed to determine the optimal target volume within the injured spinal cord for improving functional recovery and sparing tissue with stereotactic x-irradiation. METHODS: SCI was produced in rats at the T10 level. A 20-Gy dose of radiation was delivered with a single, 4-mm-diameter, circular radiation beam centered either on the injury epicenter or 4 or 8 mm caudal or rostral to the injury epicenter. Locomotor function was determined for 6 weeks with the Basso, Beattie, and Bresnahan locomotor scale and tissue sparing by histological analysis of transverse sections along the spinal cords. RESULTS: X-irradiation of spinal cord segments at 4 mm, but not 8 mm, caudal or rostral to the contusion epicenter resulted in increases in locomotor recovery. Consistently, significant tissue sparing also occurred with x-irradiation centered at those sites, although irradiation centered 4 mm rostral to the epicenter led to tissue sparing along the greatest length of the spinal cord. Interestingly, regression analysis of these variables demonstrated that the quantitative relationship between the amount of tissue spared and the improvement in locomotion recovery was greatest in a region several millimeters rostral to the injury epicenter. CONCLUSIONS: These results indicate that x-irradiation in a region rostral to the injury epicenter is optimal for recovery from SCI. This minimal target should be attractive for therapeutic application since it allows a greatly reduced target volume so that uninjured tissue is not needlessly irradiated