The influence of functional pinealectomy and exogenous melatonin application on healing of a burr hole in adult rat calvaria: a histological and immunohistochemical study

Abstract

Background: 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. but 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. Materials and methods:The total of 30 adult female Wistar-Albino rats was randomly divided into three groups (n = 10): control (CO) group (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 plus 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 hematoxylin/eosin-stained and mallory azan slices applied in anti-bone sialoprotein (BSP). Image Pro Express 4.5 program 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.Results: 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 vascularization, it was observed that the most vascular structure was found in the Px+MEL group among the scar tissue and ossification areas, while the vascularization was the least in the Px group (p < 0.001). Conclusions: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 utilization of MEL may improve the bone repair in calvarial defects.

Histological and Immunohistochemical Analysis of the Effects of Topical Melatonin Treatment Associated with Collagen Sponge and rhBMP-2 Protein on Bone Remodeling

“…The authors stated that melatonin exerts an osteogenic effect, while rhBMP-2 provides osteoinduction, and the collagen sponge provides osteoconduction. Currently, melatonin is known to have properties related to bone metabolism, and its use favors bone repair due to osteogenic and antiosteoclastic properties [ 9 , 36 , 37 , 38 ].…”

Análise morfológica dos efeitos do tratamento tópico da melatonina associada à esponja de colágeno e à proteína rhbmp-2 sobre o remodelamento ósseo

“…Os autores afirmaram que a melatonina exerce um efeito osteogênico, enquanto que a rhBMP-2 atua por osteoindução, e a esponja de colágeno fornece osteocondução, ou seja, a primeira faz com que células mesenquimais indiferenciadas se diferenciem em tipos celulares produtores de matriz óssea e o segundo, cria um ambiente favorável para migração de células osteoapositivas. Atualmente, sabe-se que a melatonina tem propriedades relacionadas ao metabolismo ósseo, e seu uso favorece o reparo ósseo devido às propriedades osteogênicas e antiosteoclásticas (113,114,115) . Wang et al (1990) demonstraram que a dose de rhBMP-2 é crítica para a formação óssea (116) .…”