Influence of tissue compliance changes in the Cranio-cervical junction on cerebrospinal fluid dynamics

The cranio-cervical junction (CCJ) represents a critical transitional zone between the cranium and cervical spine. It is speculated that changes of tissue compliance within the CCJ may disrupt normal cerebrospinal fluid (CSF) flow, but this hypothesis has not been sufficiently validated. Therefore, this research study investigated the influence of tissue compliance changes at the CCJ on CSF dynamics and its potential role in related neurological disorders. A collagen fibrous hyperplasia model was established by injecting bleomycin (BLM) into the posterior atlanto-occipital interspace (PAOiS) in mice. After four weeks, the soft tissues of the PAOiS were harvested for histological and molecular analyses to verify the successful establishment of the animal model. A biomechanical investigation was performed to assess tissue compliance in the PAOiS. CSF pressure in the lateral ventricle was monitored to evaluate the influence of the tissue compliance changes on CSF dynamics. After BLM treatment, the deposition of collagen fibers and the expression levels of Col Iα1 and α-SMA in the PAOiS were significantly increased, which indicated that collagen fibrous hyperplasia model in mice was successfully established. Uniaxial tensile testing results revealed a significant increase of the elastic modulus in the PAOiS, indicating enhanced stiffness and reduced compliance of the PAOiS tissue. Furthermore, CSF pressure in the lateral ventricle was elevated following these changes in the PAOiS tissue. This study demonstrated that reduced tissue compliance caused by hyperplasia can disrupt normal CSF dynamics, offering new insights into the pathogenesis of neurological disorders associated with CSF dynamics.