Glymphatic System in the Central Nervous System, a Novel Therapeutic Direction Against Brain Edema After Stroke

Abstract

Stroke is the destruction of brain function and structure, and is caused by either cerebrovascular obstruction or rupture. It is a disease associated with high mortality and disability worldwide. Brain edema after stroke is an important factor affecting neurologic function recovery. The glymphatic system is a recently discovered cerebrospinal fluid (CSF) transport system. Through the perivascular space and aquaporin 4 (AQP4) on astrocytes, it promotes the exchange of CSF and interstitial fluid (ISF), clears brain metabolic waste, and maintains the stability of the internal environment within the brain. Excessive accumulation of fluid in the brain tissue causes cerebral edema, but the glymphatic system plays an important role in the process of both intake and removal of fluid within the brain. The changes in the glymphatic system after stroke may be an important contributor to brain edema. Understanding and targeting the molecular mechanisms and the role of the glymphatic system in the formation and regression of brain edema after stroke could promote the exclusion of fluids in the brain tissue and promote the recovery of neurological function in stroke patients. In this review, we will discuss the physiology of the glymphatic system, as well as the related mechanisms and therapeutic targets involved in the formation of brain edema after stroke, which could provide a new direction for research against brain edema after stroke.

D* from diffusion MRI reveals a correspondence between ventricular cerebrospinal fluid volume and flow in the ischemic rodent model

“…44,46 At this stage, the ventricles may dilate due to disruption of the CSF circulation caused by a damaged nerve system. 47 Alternatively, the CSF pressure in the ventricular structures may decrease to increase the clearance of edema, resulting in ventricle enlargement. 48 As in previous studies, our further study confirmed the effect of edema on ventricular volume through changes in ADC and edema volume (Supplementary Figure 5).…”

Molecular, Pathological, Clinical, and Therapeutic Aspects of Perihematomal Edema in Different Stages of Intracerebral Hemorrhage

“…Glymphatic and meningeal lymphatic dysfunction of the brain has been observed in patients with ischemic stroke [169][170][171]. This abnormality may promote the formation of brain edema in some neurological disorders, including ischemic stroke and subarachnoid hemorrhage.…”

Regionally Altered Immunosignals of Surfactant Protein-G, Vascular and Non-Vascular Elements of the Neurovascular Unit after Experimental Focal Cerebral Ischemia in Mice, Rats, and Sheep

“…In addition to an altered barrier function between blood and the brain’s parenchyma, the influx of cerebrospinal fluid was recognized as a significant factor for edema formation in stroke [ 13 , 14 ]. Further, the glymphatic system, representing a unique cleaning pathway that uses perivascular spaces to flush the brain’s interstitium was recently discussed to be involved in ischemia-associated edema formation [ 15 , 16 , 17 ]. In this context, a pivotal role in blood-brain barrier functionality and brain fluid homeostasis has been attributed to the aquaporin-4 (AQP4) water channel, which is typically located at the astroglial end-feet [ 18 , 19 , 20 , 21 ].…”