A Brief Overview of the Cerebrospinal Fluid System and Its Implications for Brain and Spinal Cord Diseases, 2022, Wichmann et al

[SNT Gatchaman]

A Brief Overview of the Cerebrospinal Fluid System and Its Implications for Brain and Spinal Cord Diseases
Thea Overgaard Wichmann, Helle Hasager Damkier, Michael Pedersen

A comprehensive understanding of the cerebrospinal fluid (CSF) system is essential for our understanding of health and disease within the central nervous system (CNS). The system of CSF refers to all components involved in CSF production, movement, and absorption. In recent years, extensive research has resulted in vastly improved understanding of the CSF system in health and disease. Yet, several aspects remain to be fully clarified, notably along the spinal cord as the preponderance of research has focused on the brain. This review briefly summarizes the CSF system and its implications for CNS diseases and highlights the knowledge gaps that require further research.

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[SNT Gatchaman]

The CSF system constitutes a crucial role in the CNS as it provides mechanical protection, ensures homeostasis, and facilitates communication between the CNS and peripheral nervous system, lymphatic system, vascular system, and immune system. Yet, some aspects of the CSF system remain to be fully clarified, notably along the spinal cord.

CSF is therefore not simply an ultrafiltrate of the blood, but a product of a tightly regulated ion transport that generates osmotic gradients and water transport. The production of CSF by the choroid plexi is believed to be relatively constant; however, the CSF secretion varies over the duration of a day with an average production of 650 ml and maximal production after midnight.

It is generally believed that the choroid plexi are the main sites of CSF production with contribution from extrachoroidal sites; however, it has been proposed that the extrachoroidal sites are the main sites of CSF production with contribution from the choroid plexi.

The CSF flow dynamics within the ventricular system and the subarachnoid spaces is thought to consist of two main types of movements: convective flow and pulsatile flow.

Contrary to the unidirectional movement of the convective flow, the pulsatile flow is a bidirectional movement in upward (cranial) and downward direction (caudal) along the spinal cord, and in varying directions in the brain.

The relationship between the cardiac- and respiratory- driving forces is debated as the driving forces influence arterial and venous blood flow differently, thereby contributing to CSF movement to a different extent; however, the cardiac-driven force is thought to be responsible for the basic pulsatile CSF flow, while the respiratory-driven force is responsible for the large pulsatile CSF flow.

 

[SNT Gatchaman]

An essential function of the CSF system is the maintenance of CNS homeostasis. As the CNS consists of highly active metabolic regions, waste products need to be cleared. The most recently proposed mechanism for waste clearance is the highly debated glymphatic system. The available literature primarily focuses on the mechanisms within the brain; thus, the mechanisms within the spinal cord remain largely elusive.

The role of [water channels aquaporin-4] is the most controversial part of the glymphatic system as convective transport through AQP4 is questionable from a physiological point of view. There is, however, consensus that CSF has a convective flow along the perivascular spaces of the larger blood vessels (i.e., arteries and arterioles) and diffusion across the smaller blood vessels (i.e., capillaries) situated at the neurovascular unit including AQP4.

The existence of a lymphatic network within the meninges of the brain was first described by the Italian anatomist Paolo Mascagni in 1787; a description that recently has been translated and published. With the rediscovery of the lymphatic network [in 2015], findings demonstrate that the meningeal lymphatic vessels are embedded within the dura mater alongside arteries, veins, and cranial nerves.

Although considerable anatomical differences exist between the brain and the spinal cord, it seems reasonable to assume that the spinal cord has a waste clearance system and a lymphatic system resembling the systems proposed for the brain. In support of this assumption studies have demonstrated the existence of spinal perivascular spaces in rats, the existence of meningeal lymphatic vessels along the spinal cord in mice, and expression of AQP1 and AQP4 water channels in the rodent spinal cord.

 

[SNT Gatchaman]

... a common complication of subarachnoid hemorrhage is hydrocephalus. This type of hydrocephalus was previously believed to be caused by an obstruction of the CSF flow in the cerebral aqueduct or the arachnoid granulations; however, recent studies suggest that hemorrhage causes an inflammation-dependent hypersecretion of CSF by the choroid plexi.

Disturbances in the CSF movement may influence the functioning of the waste clearance system. Thus, CNS diseases causing an obstruction in the brain or along the spinal cord, and thereby CSF movement disturbances, may promote the emergence and progress of secondary CNS diseases.

As the preponderance of studies investigate the mechanisms of the CSF system and its implications for neurological diseases in the brain, our understanding is sparse when it comes to the mechanisms in the spinal cord.