Ependymal Cilia: Physiology and Role in Hydrocephalus

Abstract

Cerebrospinal fluid (CSF), a colorless liquid that generally circulates from the lateral ventricles to the third and fourth ventricles, provides essential nutrients for brain homeostasis and growth factors during development. As evidenced by an increasing corpus of research, CSF serves a range of important functions. While it is considered that decreased CSF flow is associated to the development of hydrocephalus, it has recently been postulated that motile cilia, which line the apical surfaces of ependymal cells (ECs), play a role in stimulating CSF circulation by cilia beating. Ependymal cilia protrude from ECs, and their synchronous pulsing transports CSF from the lateral ventricle to the third and fourth ventricles, and then to the subarachnoid cavity for absorption. As a result, we postulated that malfunctioning ependymal cilia could disrupt normal CSF flow, raising the risk of hydrocephalus. This review aims to demonstrate the physiological functions of ependymal cilia, as well as how cilia immobility or disorientation causes problems. We also conclude conceivable ways of treatment of hydrocephalus currently for clinical application and provide theoretical support for regimen improvements by investigating the relationship between ependymal cilia and hydrocephalus development.

Keywords: cerebrospinal fluid; ependymal cilia; hydrocephalus; pathogenesis; treatment.

FIGURE 1

Functions of ependymal cilia. Ependymal cilia protrude from ependymal cells, and their synchronized pulsing transports CSF from the lateral ventricle to the third and fourth ventricles, where it is absorbed. Adult ependymal cells’ apical enrichment of actin in centriolar plaques aids in the maintenance of the optimal number and spacing of centrioles, allowing ependymal cells to maintain an ideal number of motile cilia and thus aid in CSF nutrition exchange and waste clearance, assisting in CSF homeostasis. Furthermore, the beating of ependymal cilia can propel CSF flow and create a concentration gradient of guiding molecules, which aids neuroblast migration orientation. CSF, cerebrospinal fluid.

FIGURE 2

Abnormalities of ependymal cilia. The absence of cilia, cilia immobility, and changes in planar polarity that modify the direction of the cilia’s beat are all examples of ciliary disorders. (A) Cilia loss occurs when the number of ependymal cilia decreases, their length decreases, or there are no cilia at all. FoxJ1, Mcidas, GemC1, NHERF1, Odf2, CCNO, NME7, and HTT are all related genes. (B) Furthermore, the structure of the original normal cilia is destroyed, as is the aberrant function of the dynein arms and axonemes, resulting in ependymal cilia immobility. DNAAFFs, CCDC151, and DNA Polλ (DPCD) are all related genes. In addition, aberrant cilia function in the ependyma causes inappropriate CSF accumulation. (C) Ciliary movement frequency will be reduced by Hydin, CFAP221 and CFAP54, and regular PCP disorder will be harmed. CCNO, Cyclin O; NME7, non-metastatic cell 7; HTT, Huntington protein; LRRC6, leucine-rich repeat-containing protein 6; DNAAFs, dynein axonemal assembly factors; CFAP221, cilia-and flagella-associated protein 221; CFAP54, cilia-and flagella-associated protein 54; DVLs, disheveled.

FIGURE 3

Pathophysiology of motile cilia in hydrocephalus. Abnormal motile cilia can be caused by a variety of reasons. (A) Alcohol abuse may reduce the beating frequency of cilia, resulting in slower CSF flow. (B) Degenerative neuropathologies, such as Alzheimer’s disease, can obstruct the clearance of toxic molecules like Aβ, causing them to accumulate in the ventricle. (C) Furthermore, PCD patients’ ependymal cilia are unable to beat at a regular frequency, which contributes to a disruption in normal CSF circulation. (D) Concussion brain injury also contributes to the rapid shedding of ventricular ependymal cilia and the reduction of CSF flow frequency.