Yokogawa Noriaki, Murakami Hideki, Demura Satoru, Kato Satoshi, Yoshioka Katsuhito, Yamamoto Miyuki, Iseki Shoichi, Tsuchiya Hiroyuki
Department of Orthopaedic Surgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Japan.
Department of Histology and Embryology, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Japan.
PLoS One. 2015 Jul 27;10(7):e0133806. doi: 10.1371/journal.pone.0133806. eCollection 2015.
Spinal 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.
The 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.
In 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.
In 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.
在先前接受过放射治疗的区域进行脊柱手术会增加围手术期并发症的风险,如伤口愈合延迟或伤口感染。此外,临床上常观察到硬脑膜周围粘连。因此,类似于辐射诱导的纤维化(其他组织中的一种主要晚期辐射损伤),预计脊柱放疗后会发生硬膜外纤维化。在本研究中,我们对小鼠脊柱硬脑膜和硬膜外组织的放疗后变化进行了组织病理学评估。
对ddY小鼠的胸腰段交界处给予单次10或20 Gy的照射。切除照射后的脊柱后,评估硬膜外纤维化的发生情况以及硬脑膜中转化生长因子β1的表达。此外,使用电子显微镜评估硬脑膜和硬膜外组织的微观结构。
在接受20 Gy照射的小鼠中,硬膜外纤维化在照射后约12周首次出现,从照射后16周起在所有病例中均观察到。相比之下,未照射的小鼠未观察到硬膜外纤维化。与未照射的小鼠相比,接受10和20 Gy照射的小鼠在照射后1周和照射后期转化生长因子β1的过表达明显更多。在微观结构评估中,与未照射的小鼠相比,照射后12周和24周蛛网膜屏障细胞层变薄。
在小鼠中,高剂量照射后晚期会发生脊柱硬膜外纤维化,转化生长因子β1的过表达与其他组织中辐射诱导的纤维化情况类似。此外,照射后期观察到蛛网膜屏障细胞层变薄。因此,应考虑这些现象可能作为脊柱辐射诱导损伤而发生的可能性。