title: Biomarkers of traumatic injury are transported from brain to blood via the glymphatic system.
abstract: The nonspecific and variable presentation of traumatic brain injury (TBI) has motivated an intense search for blood-based biomarkers that can objectively predict the severity of injury. However, it is not known how cytosolic proteins released from traumatized brain tissue reach the peripheral blood. Here we show in a murine TBI model that CSF movement through the recently characterized glymphatic pathway transports biomarkers to blood via the cervical lymphatics. Clinically relevant manipulation of glymphatic activity, including sleep deprivation and cisternotomy, suppressed or eliminated TBI-induced increases in serum S100β, GFAP, and neuron specific enolase. We conclude that routine TBI patient management may limit the clinical utility of blood-based biomarkers because their brain-to-blood transport depends on glymphatic activity.
authors.affiliation: Center for Translational Neuromedicine, Department of Neurosurgery and Department of Pathology, University of Rochester Medical Center, Rochester, New York 14642.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Plog
authors.affiliation: Center for Translational Neuromedicine, Department of Neurosurgery and.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Dashnaw
authors.affiliation: Center for Translational Neuromedicine, Department of Neurosurgery and.
authors.forename: Emi
authors.initials: E
authors.lastname: Hitomi
authors.affiliation: Center for Translational Neuromedicine, Department of Neurosurgery and.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Peng
authors.affiliation: Center for Translational Neuromedicine, Department of Neurosurgery and.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Center for Translational Neuromedicine, Department of Neurosurgery and.
authors.forename: Nanhong
authors.initials: N
authors.lastname: Lou
authors.affiliation: Center for Translational Neuromedicine, Department of Neurosurgery and.
authors.forename: Rashid
authors.initials: R
authors.lastname: Deane
authors.affiliation: Center for Translational Neuromedicine, Department of Neurosurgery and Maiken_Nedergaard@URMC.Rochester.edu.
authors.forename: Maiken
authors.identifier: http://orcid.org/0000-0001-6502-6031
authors.initials: M
authors.lastname: Nedergaard
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D001812:Blood-Brain Barrier / Q000378:metabolism; D001930:Brain Injuries / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D045604:Extracellular Fluid / Q000378:metabolism*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000097:blood / Q000134:cerebrospinal fluid; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000378:metabolism; D064568:S100 Calcium Binding Protein beta Subunit / Q000097:blood / Q000134:cerebrospinal fluid; D012892:Sleep Deprivation / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism
chemical_list: D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D064568:S100 Calcium Binding Protein beta Subunit
keywords: CSF; biomarker; clearance; lymphatic; traumatic brain injury