Department of Histology and Embryology, Adnan Menderes University, Faculty of Medicine, Aydın, Turkey.
Department of Neurosurgery, Adnan Menderes University, Faculty of Medicine, Aydın, Turkey.
Folia Morphol (Warsz). 2022;81(2):271-279. doi: 10.5603/FM.a2021.0047. Epub 2021 May 17.
Even today, repair of the cranial defects still represents a significant challenge in neurosurgery and various options have been used for their reconstruction to date. However, there are very few studies investigating the effects of exogenous administration of melatonin (MEL) as an agent that promotes bone regeneration. The goal of this study was to investigate the effects of functional pinealectomy (Px) and exogenous MEL administration on the bone repair properties and surrounding connective tissue alterations in a rat calvaria model.
The total of 30 adult female Wistar-Albino rats was randomly divided into three groups (n = 10): control group (CO; 12 h light/12 h dark exposure), functional Px group (24 h light exposure, light-induced functional Px), and Px+MEL group (light-induced Px + MEL, 20 mg/kg/day for 12 weeks). Critical-sized burr-hole defects (diameter: 3.0 mm) were surgically created by a single operator in the calvarium of all rats, using an electric drill. Animals in Px+MEL group received MEL 20 mg/kg/day for 12 weeks. At the end of the study, bone healing and connective tissue alterations surrounding drilled defect area in the rat calvaria were determined in haematoxylin-eosin-stained and Mallory Azan slices applied in anti-bone sialoprotein. Image Pro Express 4.5 programme was used for histomorphometric calculation of areas of new bone and fibrotic tissue. Normality control was performed by Shapiro-Wilk test. Variance homogeneities were examined by Shapiro-Wilk and Levene tests; Tukey HSD test was used as a post hoc method since there was no homogeneity problem. All hypothesis tests were performed at the 0.05 significance level.
Histological analysis showed that the bone repair process in the Px+MEL group was similar to that of the CO group, whereas the functional Px group showed a delay. Histomorphometrically, it was found that the Px group had the largest hole diameter and the most fibrotic scar area, although no binary statistical significance was found between the CO and Px+MEL groups (p = 0.910). In terms of vascularisation, it was observed that the most vascular structure was found in the Px+MEL group among the scar tissue and ossification areas, while the vascularisation was the least in the Px group (p < 0.001).
Our findings revealed that bone repair process was impaired in functional Px group, but exogenous MEL replacement was able to restore this response. Thus, it is concluded that utilisation of MEL may improve the bone repair in calvarial defects.
即使在今天，颅骨缺损的修复仍然是神经外科的一个重大挑战，迄今为止已经有各种选择被用于其重建。然而，很少有研究调查外源性褪黑素（MEL）给药作为促进骨再生的药物的效果。本研究的目的是研究功能性松果体切除术（Px）和外源性 MEL 给药对大鼠颅骨模型中骨修复特性和周围结缔组织改变的影响。
总共 30 只成年雌性 Wistar-Albino 大鼠被随机分为三组（n = 10）：对照组（CO；12 小时光照/12 小时黑暗暴露）、功能性 Px 组（24 小时光照，光诱导功能性 Px）和 Px+MEL 组（光诱导 Px+MEL，每天 20mg/kg，持续 12 周）。所有大鼠颅骨均由一名手术医生使用电钻手术创建临界尺寸的骨孔缺陷（直径：3.0mm）。在 Px+MEL 组中，动物每天接受 20mg/kg 的 MEL 治疗 12 周。在研究结束时，通过苏木精-伊红染色和 Mallory Azan 切片在抗骨涎蛋白中确定大鼠颅骨钻孔缺陷区域的骨愈合和周围结缔组织改变。使用 Image Pro Express 4.5 程序对新骨和纤维组织区域进行组织形态计量学计算。通过 Shapiro-Wilk 检验进行正态性控制。方差同质性通过 Shapiro-Wilk 和 Levene 检验进行检查；由于不存在同质性问题，因此使用 Tukey HSD 检验作为事后检验方法。所有假设检验均在 0.05 显著性水平下进行。
组织学分析表明，与 CO 组相比，Px+MEL 组的骨修复过程相似，而功能性 Px 组则表现出延迟。组织形态计量学结果表明，尽管 CO 和 Px+MEL 组之间没有二进制统计学意义（p = 0.910），但 Px 组的孔直径最大，纤维疤痕面积最大。在血管生成方面，观察到在疤痕组织和骨化区域中，最血管化的结构存在于 Px+MEL 组中，而在 Px 组中血管生成最少（p<0.001）。
我们的研究结果表明，功能性 Px 组的骨修复过程受损，但外源性 MEL 替代能够恢复这种反应。因此，我们得出结论，使用 MEL 可能会改善颅骨缺损的骨修复。
