The role of glymphatic system in the cerebral edema formation after ischemic stroke

Cerebral edema following ischemic stroke is predictive of the severity of the eventual stroke related damage, however the effective treatment is limited. The glymphatic system is a recently identified waste clearance pathway in the brain, found in the paravascular space and mainly composed of astrocytes and their aquaporin-4 (AQP4) water channels. In this review, we primarily focus on the role of the glymphatic system in the formation of cerebral edema after ischemic stroke. There is still no definite conclusion whether the influx of cerebrospinal fluid (CSF) in the glymphatic system is increased or not after ischemic stroke. However, the reduced interstitial fluid (ISF) clearance after ischemic stroke is definite. Additionally, AQP4 as the most important part of glymphatic system plays a complex bimodal in cerebral edema after ischemic stroke. Most of the research has found that AQP4 deletion in animals reduces cerebral edema after acute ischemic stroke compared with wild type animal models. The mislocalization of astrocytic AQP4 was also presented after ischemic stroke. As the cerebral edema after ischemic stroke is difficult to treat, we discuss several potential treatment targets related to glymphatic system. More studies are needed to explore the role of glymphatic system in the formation of cerebral edema after ischemic stroke and develop probable treatment strategies.