Water channels in the brain and spinal cord-overview of the role of aquaporins in traumatic brain injury and traumatic spinal cord injury

Abstract

Knowledge about the mechanisms underlying the fluid flow in the brain and spinal cord is essential for discovering the mechanisms implicated in the pathophysiology of central nervous system diseases. During recent years, research has highlighted the complexity of the fluid flow movement in the brain through a glymphatic system and a lymphatic network. Less is known about these pathways in the spinal cord. An important aspect of fluid flow movement through the glymphatic pathway is the role of water channels, especially aquaporin 1 and 4. This review provides an overview of the role of these aquaporins in brain and spinal cord, and give a short introduction to the fluid flow in brain and spinal cord during in the healthy brain and spinal cord as well as during traumatic brain and spinal cord injury. Finally, this review gives an overview of the current knowledge about the role of aquaporins in traumatic brain and spinal cord injury, highlighting some of the complexities and knowledge gaps in the field.

Keywords: aquaporins; glymphatic system; lymphatic network; traumatic brain injury; traumatic spinal cord injury.

Figure 1

The fluid compartments of the central nervous system can be subdivided into four compartments: blood, interstitial fluid (ISF), intracellular fluid, and cerebrospinal fluid (CSF). The CSF is mainly produced by the choroid plexus in the lateral ventricles of the brain. The epithelial cells are connected by tight junctions, thereby creating the blood-CSF barrier. The brain vasculature is covered by a layer of endothelial cells connected by tight junctions, a basement membrane, and a densely packed layer of astrocytic end-feet and pericytes, thereby creating the blood–brain barrier. Surrounding the vasculature are the perivascular spaces. CSF is thought to enter from the perivascular spaces surrounding arteries (A) and flow into the brain parenchyma through AQP4 water channels located at the astrocytic end-feet (B,C). Within the brain parenchyma, CSF disperses and intermixes with ISF and waste products. The mixture enters the perivascular spaces surrounding veins by unknown mechanisms, e.g., AQP4 water channels. From the perivascular spaces, the mixture leaves the brain parenchyma. These mechanisms have been extensively studied etc. It seems, however, reasonable to believe that similar mechanisms are present in the spinal cord.

Figure 2

Aquaporins (AQPs) are found in the brain and spinal cord. In the brain AQP1 is expressed by the cells of choroid plexus (purple markers, A), while AQP1 is expressed throughout the spinal cord; however, most prominent in laminae I and II in the dorsal horn. AQP4 (blue markers) is expressed throughout the brain and spinal cord (B), notably the astrocytic end-feet (C), but also throughout the white and gray matter of the brain and spinal cord (B).