title: Drowning stars: reassessing the role of astrocytes in brain edema.
abstract: Edema formation frequently complicates brain infarction, tumors, and trauma. Despite the significant mortality of this condition, current treatment options are often ineffective or incompletely understood. Recent studies have revealed the existence of a brain-wide paravascular pathway for cerebrospinal (CSF) and interstitial fluid (ISF) exchange. The current review critically examines the contribution of this 'glymphatic' system to the main types of brain edema. We propose that in cytotoxic edema, energy depletion enhances glymphatic CSF influx, whilst suppressing ISF efflux. We also argue that paravascular inflammation or 'paravasculitis' plays a critical role in vasogenic edema. Finally, recent advances in diagnostic imaging of glymphatic function may hold the key to defining the edema profile of individual patients, and thus enable more targeted therapy.
authors.affiliation: Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, New York 14642, USA; Department of Ophthalmology, Haukeland University Hospital, Bergen 5021, Norway; Letten Centre, Institute of Basic Medical Sciences, Department of Physiology, University of Oslo, 0317 Oslo, Norway. Electronic address: alexander.thrane@gmail.com.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Thrane
authors.affiliation: Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, New York 14642, USA; Department of Ophthalmology, Haukeland University Hospital, Bergen 5021, Norway; Letten Centre, Institute of Basic Medical Sciences, Department of Physiology, University of Oslo, 0317 Oslo, Norway.
authors.forename: Vinita
authors.initials: V
authors.lastname: Rangroo Thrane
authors.affiliation: Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, New York 14642, USA.
authors.forename: Maiken
authors.initials: M
authors.lastname: Nedergaard
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology*; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001929:Brain Edema / Q000378:metabolism / Q000473:pathology*; D002555:Cerebrospinal Fluid / Q000378:metabolism*; D045604:Extracellular Fluid / Q000378:metabolism*; D006801:Humans
keywords: aquaporin-4; astrocyte; cerebral edema; glymphatic; paravascular