Biomarkers of traumatic injury are transported from brain to blood via the glymphatic system
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....
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| Veröffentlicht in: | The Journal of neuroscience 2015-01, Vol.35 (2), p.518-526 |
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| container_title | The Journal of neuroscience |
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| creator | Plog, Benjamin A Dashnaw, Matthew L Hitomi, Emi Peng, Weiguo Liao, Yonghong Lou, Nanhong Deane, Rashid Nedergaard, Maiken |
| description | 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. |
| doi_str_mv | 10.1523/JNEUROSCI.3742-14.2015 |
| format | Article |
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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.</description><subject>Animals</subject><subject>Biomarkers - blood</subject><subject>Biomarkers - cerebrospinal fluid</subject><subject>Blood-Brain Barrier - metabolism</subject><subject>Brain Injuries - blood</subject><subject>Brain Injuries - cerebrospinal fluid</subject><subject>Brain Injuries - metabolism</subject><subject>Extracellular Fluid - metabolism</subject><subject>Female</subject><subject>Glial Fibrillary Acidic Protein - blood</subject><subject>Glial Fibrillary Acidic Protein - cerebrospinal fluid</subject><subject>Metabolic Clearance Rate</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Neuroglia - metabolism</subject><subject>S100 Calcium Binding Protein beta Subunit - blood</subject><subject>S100 Calcium Binding Protein beta Subunit - cerebrospinal fluid</subject><subject>Sleep Deprivation - blood</subject><subject>Sleep Deprivation - cerebrospinal fluid</subject><subject>Sleep Deprivation - metabolism</subject><issn>0270-6474</issn><issn>1529-2401</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUFv1DAQhS1ERbeFv1D5yCVbj-3E8QUJVi0UVa0E9IZkOc6465LEi51U2n9PQssKTpxGmnnv6Y0-Qs6AraHk4vzzzcXdl9uvm6u1UJIXINecQfmCrOarLrhk8JKsGFesqKSSx-Qk5wfGmGKgXpFjXpa1VlKtyPcPIfY2_cCUafR0THbq7RgcDcPDlPbUJlyWQ97FNGJLfYo9bZINAx0jbboYW_oYLB23SO-7fb_b_nbnfR6xf02OvO0yvnmep-Tu8uLb5lNxffvxavP-unAV6LFovKicaJrG1zUqDRU6rWuYZ6m1Fp614LFuhHAKENsSlNU1B-a8R8ehEqfk3VPubmp6bB0Oc-XO7FKYX9ubaIP59zKErbmPj0ZyLSSr54C3zwEp_pwwj6YP2WHX2QHjlA2oqtRq1vL_S6sZj6q5WGpVT1KXYs4J_aERMLNQNAeKZqFoQJqF4mw8-_ufg-0PNvELyeKcIw</recordid><startdate>20150114</startdate><enddate>20150114</enddate><creator>Plog, Benjamin A</creator><creator>Dashnaw, Matthew L</creator><creator>Hitomi, Emi</creator><creator>Peng, Weiguo</creator><creator>Liao, Yonghong</creator><creator>Lou, Nanhong</creator><creator>Deane, Rashid</creator><creator>Nedergaard, Maiken</creator><general>Society for Neuroscience</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7TK</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-6502-6031</orcidid></search><sort><creationdate>20150114</creationdate><title>Biomarkers of traumatic injury are transported from brain to blood via the glymphatic system</title><author>Plog, Benjamin A ; 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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Animals Biomarkers - blood Biomarkers - cerebrospinal fluid Blood-Brain Barrier - metabolism Brain Injuries - blood Brain Injuries - cerebrospinal fluid Brain Injuries - metabolism Extracellular Fluid - metabolism Female Glial Fibrillary Acidic Protein - blood Glial Fibrillary Acidic Protein - cerebrospinal fluid Metabolic Clearance Rate Mice Mice, Inbred C57BL Neuroglia - metabolism S100 Calcium Binding Protein beta Subunit - blood S100 Calcium Binding Protein beta Subunit - cerebrospinal fluid Sleep Deprivation - blood Sleep Deprivation - cerebrospinal fluid Sleep Deprivation - metabolism |
| title | Biomarkers of traumatic injury are transported from brain to blood via the glymphatic system |
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