Influencing factors of glymphatic system during perioperative period

Abstract

The glymphatic system is a functional cerebrospinal fluid circulatory system that uses peri-arterial space for inflow of cerebrospinal fluid and peri-venous space for efflux of cerebrospinal fluid from brain parenchyma. This brain-wide fluid transport pathway facilitates the exchange between cerebrospinal fluid and interstitial fluid and clears metabolic waste from the metabolically active brain. Multiple lines of work show that the glymphatic system is crucial to normal brain functions, and the dysfunction of the glymphatic system is closely associated with various neurological disorders, including aging, neurodegeneration, and acute brain injury. Currently, it is common to explore the functional and molecular mechanisms of the glymphatic system based on animal models. The function of glymphatic system during perioperative period is affected by many factors such as physiological, pathological, anesthetic and operative methods. To provide a reference for the interpretation of the results of glymphatic system studies during perioperative period, this article comprehensively reviews the physiological and pathological factors that interfere with the function of the glymphatic system during perioperative period, investigates the effects of anesthetic drugs on glymphatic system function and the potential underlying mechanisms, describes operative methods that interfere with the function of the glymphatic system, and potential intervention strategies based on the glymphatic system. Future, these variables should be taken into account as critical covariates in the design of functional studies on the glymphatic system.

Keywords: AQP4; anesthetic drugs; cerebrospinal fluid; glymphatic system; pathology; perioperative; physiology.

FIGURE 1

A schematic diagram of the Glymphatic system. The glymphatic system is a brain-wide paravascular pathway that is responsible for clearing interstitial solutes. The glymphatic system consists of four functional processes. Firstly, cerebrospinal fluid (CSF) enters by bulk flow into the periarterial spaces surrounding the arteries that penetrate deep into the brain parenchyma. Here, the perivascular spaces are utilized as “highways” for fast transport of CSF into deep brain regions. Secondly, CSF enters the brain parenchyma from the periarterial spaces. Here, the movement of CSF into the parenchyma is facilitated by the aquaporin-4 (AQP4). Under physiological conditions, AQP4 is mainly expressed on the astrocytic endfeet lining the perivascular space. Thirdly, Cerebrospinal fluid and intertissue fluid (ISF) are exchanged within the brain parenchyma. However, the form of CSF/ISF flow in the brain parenchyma is still controversial. Fourthly, neurotoxic and metabolic wastes from the ISF re-enter the CSF via the perivenous spaces. Eventually, the cerebrospinal fluid containing neurotoxic and metabolic wastes flows through the meningeal lymphatic vessels to the cervical lymph nodes.

FIGURE 2

Physiological factors affecting the function of the Glymphatic system.