Abstract
PurposeSpinal surgery in a previously irradiated field carries increased risk of perioperative complications, such as delayed wound healing or wound infection. In addition, adhesion around the dura mater is often observed clinically. Therefore, similar to radiation-induced fibrosis—a major late-stage radiation injury in other tissue—epidural fibrosis is anticipated to occur after spinal radiation. In this study, we performed histopathologic assessment of postirradiation changes in the spinal dura mater and peridural tissue in mice.Materials and MethodsThe thoracolumbar transition of ddY mice was irradiated with a single dose of 10 or 20 Gy. After resection of the irradiated spine, occurrence of epidural fibrosis and expression of transforming growth factor beta 1 in the spinal dura mater were evaluated. In addition, microstructures in the spinal dura mater and peridural tissue were assessed using an electron microscope.ResultsIn the 20-Gy irradiated mice, epidural fibrosis first occurred around 12 weeks postirradiation, and was observed in all cases from 16 weeks postirradiation. In contrast, epidural fibrosis was not observed in the nonirradiated mice. Compared with the nonirradiated mice, the 10- and 20-Gy irradiated mice had significantly more overexpression of transforming growth factor beta 1 at 1 week postirradiation and in the late stages after irradiation. In microstructural assessment, the arachnoid barrier cell layer was thinned at 12 and 24 weeks postirradiation compared with that in the nonirradiated mice.ConclusionIn mice, spinal epidural fibrosis develops in the late stages after high-dose irradiation, and overexpression of transforming growth factor beta 1 occurs in a manner similar to that seen in radiation-induced fibrosis in other tissue. Additionally, thinning of the arachnoid barrier cell layer was observed in the late stages after irradiation. Thus, consideration should be given to the possibility that these phenomena can occur as radiation-induced injuries of the spine.
Highlights
Radiotherapy has been widely used for spinal metastases [1, 2], and is often performed as palliative treatment to improve patient quality of life by alleviating pain, mitigating nerve compression symptoms, and decreasing the likelihood of pathological bone fracture through local tumor control [3,4,5]
Epidural fibrosis was not observed in the nonirradiated mice
Spinal epidural fibrosis develops in the late stages after high-dose irradiation, and overexpression of transforming growth factor beta 1 occurs in a manner similar to that seen in radiation-induced fibrosis in other tissue
Summary
Radiotherapy has been widely used for spinal metastases [1, 2], and is often performed as palliative treatment to improve patient quality of life by alleviating pain, mitigating nerve compression symptoms, and decreasing the likelihood of pathological bone fracture through local tumor control [3,4,5]. Full consideration must be given to adverse events associated with radiotherapy, especially late-stage radiation injury in long-term survivors. Effective treatments for late-stage radiation injury are lacking, and such injuries may develop into life-threatening complications [6, 7]. Recurrence of pain and nerve compression due to local tumor relapse after radiotherapy is a problem for long-term survivors of spinal metastases. We performed histopathologic assessment of temporal changes in the spinal dura mater and peridural tissue following irradiation in mice, with a focus on epidural fibrosis
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