Continuous Hypodynamic Change of Cerebrospinal Fluid Flow as A Potential Factor Working for Experimental Scoliotic Formation

Abstract

Scoliosis is often associated with syringomyelia (SM). As an important role in SM formation, the influence from abnormal cerebrospinal fluid (CSF) flow is still unclear to scoliosis. The aim of this experimental work is to explore the connection between CSF flow and scoliosis through imaging and histological analysis on the basis of a kaolin-induced scoliotic rabbit model. For imaging observation, in 40 kaolin-induced rabbits by C7 spinal cord injection, through pre-and postoperative MRI and radiography, CSF flow and scoliosis formation were detected at consecutive phases. According to the final formation of scoliosis until postoperative week 12, the kaolin-induced rabbits were divided into 2 groups. Through comparing the 2 groups, the relationship between the changes of CSF flow velocity and scoliosis formation were reviewed and analyzed. For histological observation, another 20 kaolininduced rabbits were used for consecutive histological observations of spinal cord at postoperative 3-day, 2-week, 4-week and 6-week. After kaolin-induction, abnormal spinal coronal curve was observed from postoperative week 6 in the 37 survived rabbits. At postoperative week 12, scoliosis formation was detected in 73.0% kaolin-induced rabbits and the mean Cobb angle was 27.4°. From the comparison between scoliotic and non-scoliotic groups, the difference of the velocities of CSF flow was more obviously from postoperative week 4 to 12, especially after week 6. In the scoliotic group, the peak velocity of CSF flow was diseased gradually following scoliosis formation after induction. Moreover, the decrease of the peak velocities of CSF flow from preoperation to postoperative 12 weeks (ΔVmax), including up-flow (ΔVUmax) and down-flow (ΔVDmax), were positively correlated to the final scoliotic cobb angle (P < 0.01). Through histological observation at different phases, the distinctive pathological changes of the spinal cord included early inflammatory reaction, adhesion and blockage in the subarachnoid space and the central canal, perivascular space enlargement, central canal expansion, which suggested the CSF flow being blocked by multiple ways after kaolin-induction. In conclusion, experimental scoliosis can be successfully induced by intraspinal kaolin injection. In this model, continuous hypodynamic change of CSF flow was correlated to the formation of scoliosis, which could be an important factor of scoliotic pathogenesis being explored furtherly.Scoliosis is often associated with syringomyelia (SM) in clinical, which can be found in 25-85% of the patients being diagnosed as SM 1 . Meanwhile, SM also can be detected by magnetic resonance imaging (MRI) in 19.5% infantile, 26% juvenile and 20% adolescent patients ever being diagnosed as idiopathic scoliosis (IS) 2 . Moreover, in the patients with severe scoliosis (Cobb angle more than 90°), the rate of associated-SM is even up to 60.4% 3 . However, the relationship between scoliosis and SM is still obscure, which has been explained as a causal link through the "paraspinal muscle den...

Cerebrospinal fluid velocity changes of idiopathic scoliosis: a preliminary study on 3-T PC-MRI and 3D-SPACE-VFAM data

“…In experimental studies, cerebrospinal fluid (CSF) flow changes and abnormal cilia motility were found and related to spinal deformity and scoliosis [6,7]. Also, protein tyrosine kinase 7 (ptk7) gene mutation causes scoliosis in the zebrafish model [4].…”

The role of scoliosis on the comorbidity and demographics of neurofibromatosis type 1 patients: A retrospective analysis of the National Inpatient Sample database

“…It is well known that the improper curvature of the spin seen in scoliosis patients can cause obstructed cerebrospinal fluid (CSF) flow from the spine to the brain. 28 Furthermore, CSF is rich in various growth factors such as vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and platelet-derived growth factor (PDGF), all of which have been shown to be elevated in the CSF in different malignant brain neoplasms. [29][30][31] The obstructed CSF flow caused by scoliosis in NF1 patients may be preventing the proper circulation of these growth factors to the brain and its associated neoplasm, decreasing the likelihood of the development of a malignant neurological neoplasm.…”

“…Comorbidity analysis demonstrated that NF1 patients with scoliosis were at a lower risk for developing malignant neurological neoplasms. It is well known that the improper curvature of the spin seen in scoliosis patients can cause obstructed cerebrospinal fluid (CSF) flow from the spine to the brain 28 . Furthermore, CSF is rich in various growth factors such as vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and platelet‐derived growth factor (PDGF), all of which have been shown to be elevated in the CSF in different malignant brain neoplasms 29–31 .…”

Intraspinal Anomalies and Their Interplay with Spinal Deformity in Early Onset Scoliosis

“…32 Additionally, CSF flow alterations have been identified as a potential initiator for the development of spinal deformity. 64 However, further research is needed to investigate and better elucidate the underlying mechanisms of spinal deformity development and propagation in children with Chiari I malformations.…”