LABORATORY INVESTIGATION J Neurosurg Spine 32:649–656, 2020 S tereotactic radiosurgery is presently used for a variety of clinical applications in areas such as on- cology and neurosurgery, since it has an advantage over conventional methods in that specifcally defned tis- sue targets can be noninvasively treated while avoiding damage to surrounding tissue. Recently, another potential application was revealed when, in an experimental model of contusion injury, stereotactic x-irradiation of several segments of an injured spinal cord with a relatively low dose—i.e., 10 Gy—was shown to exert a neuroprotective effect while enhancing the recovery of locomotor function and sparing cord tissue. 32 Stereotactic x-irradiation is a potentially superior thera- peutic modality for spinal cord injury (SCI), with several advantages compared to current steroid treatment with methylprednisolone. X-rays can completely penetrate in- jured spinal cord tissue without requiring compromised circulation for delivery of the therapeutic agent, as in the case of systemically administered methylprednisolone, thereby avoiding undesired side effects, such as myopathy and immunosuppression, in noncord tissues. 23 Targeted x- irradiation may also be benefcial both by expanding the volume of injured tissue that can be treated and the dura- tion of the therapeutic time window, 30 each of which can be decreased by compromised circulation due to injury. In the experiments in which stereotactic x-irradiation of injured spinal cord tissue enhanced locomotor recovery and spared cord tissue after contusion injury, 32 the injured spinal cord was identifed as the therapeutic target of irra- diation, rather than surrounding noncord tissue. However, the precise anatomical location of cord tissue necessary to show a beneft from radiosurgery in relation to the site of ABBREVIATIONS BBB = Basso, Beattie, and Bresnahan; SCI = spinal cord injury. SUBMITTED March 18, 2019. ACCEPTED November 5, 2019. INCLUDE WHEN CITING Published online January 3, 2020; DOI: 10.3171/2019.11.SPINE19305. Therapeutic target for external beam x-irradiation in experimental spinal cord injury Richard J. Zeman, PhD, 1 Xialing Wen, MS, 1 Chitti R. Moorthy, MD, 2 and Joseph D. Etlinger, PhD 1 Departments of 1 Cell Biology and Anatomy and 2 Radiation Medicine, New York Medical College, Valhalla, New York OBJECTIVE X-irradiation has been shown to be benefcial to recovery from spinal cord injury (SCI); however, the opti - mal therapeutic target has not been defned. 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, signifcant tissue sparing also occurred with x-irradiation cen- tered 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 relation- ship 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 vol- ume so that uninjured tissue is not needlessly irradiated. https://thejns.org/doi/abs/10.3171/2019.11.SPINE19305 KEYWORDS spinal cord injury; contusion; locomotor function; cavitation; stereotactic x-irradiation J Neurosurg Spine Volume 32 • May 2020 649 ©AANS 2020, except where prohibited by US copyright law Unauthenticated | Downloaded 09/18/21 01:43 PM UTC