Osteogenesis imperfecta (OI) is a complex disease caused by changes in connective tissue composition, leading to bone fragility. The pathophysiology of this disorder is highly diverse, involving a range of genetic variables and a variety of phenotypic symptoms, including neurological impairment.Our research focused on the possible alteration that occurred in the Central Nervous System (CNS) of an in vivo model of OI, using male and female adult Brtl-/+ mice. Histochemical techniques were employed to investigate the morphological changes of CNS, through Hematoxylin & Eosin and Picrosirius red stainings. A wide range of microscopy techniques, such as bright-field, polarized light and transmission electron microscopy (TEM), were used to investigate the modification of brain tissue organization, cellular changes and ultrastructural alterations. Parallelly, we focused our attention on the potential changes in the oxidative stress pathway, using immunohistochemical reactions to analyze the expression levels of COX4, GPX4, and SOD2 enzymes.By doing so, we detected a strong alteration of CNS cytoarchitecture, with a profound change in the expression of collagen fibres, clearly detectable in mutant mice. The investigated markers of oxidative stress appeared strongly correlated to the severity of the disease. Through this work, it is possible to enhance our understanding of the link between genetic anomalies, bone fragility, and neurological involvement in OI, paving the way for future research.