Role of ependymal cilia impairment in syringomyelia formation and its potential mechanism

Abstract

Syringomyelia is characterized by the dilation of the central canal (CC) in the spinal cord, which is often secondary to Chiari malformation (CMI), tumor and other spinal cord-compression diseases. The majority of hypotheses regarding the pathogenesis of syringomyelia center on the complex cerebrospinal fluid (CSF) circulation disorders that result from subarachnoid space (SAS) obstruction. However, even after the SAS obstruction is relieved in syringomyelia patients, the condition rarely disappears completely. Furthermore, obstructing the CSF in SAS in rats has failed to induce syringomyelia, challenging the traditional theory of syringomyelia formation. Maintained by intercellular calcium wave (ICW) through Connexin 43 (Cx43) and protected by the actin network, ependymal cilia play a critical role in regulating CSF circulation. Several descriptive studies have reported a decline in cilia in syringomyelia, and CC dilation has been observed in Cx43-knockout mice. However, cilia impairment has not been considered a contributor to the development of syringomyelia. Here, we hypothesize that cilia impairment plays a vital role in syringomyelia formation. Primary diseases such as CMI can produce a compression force, leading to SAS obstruction and damage to Cx43. The damage of Cx43 disrupts ICW, which causes cilia disassembly and abnormality of ciliary beating, resulting in the disorganization of the actin network. The cilia then shed due to exposure of their basal body to shear stress. The cilia shedding and SAS obstruction collectively lead to CSF circulation disturbance, resulting in the accumulation of CSF in the CC and the formation of syringomyelia. The hypothesis provides a novel perspective on the pathophysiology of syringomyelia and may help guide future research and treatment.