title: The effects of blood and blood products on the arachnoid cell.
abstract: After traumatic brain injury (TBI), large amounts of red blood cells and hemolytic products are deposited intracranially creating debris in the cerebrospinal fluid (CSF). This debris, which includes heme and bilirubin, is cleared via the arachnoid granulations and lymphatic systems. However, the mechanisms by which erythrocytes and their breakdown products interfere with normal CSF dynamics remain poorly defined. The purpose of this study was to model in vitro how blood breakdown products affect arachnoid cells at the CSF-blood barrier, and the extent to which the resorption of CSF into the venous drainage system is mechanically impaired following TBI. Arachnoid cells were grown to confluency on permeable membranes. Rates of growth and apoptosis were measured in the presence of blood and lysed blood, changes in transepithelial electrical resistance (TEER) was measured in the presence of blood and hemoglobin, and small molecule permeability was determined in the presence of blood, lysed blood, bilirubin, and biliverdin. These results were directly compared with an established rat brain endothelial cell line (RBEC4) co-cultured with rat brain astrocytes. We found that arachnoid cells grown in the presence of whole or lysed erythrocytes had significantly slower growth rates than controls. Bilirubin and biliverdin, despite their low solubilities, altered the paracellular transport of arachnoid cells more than the acute blood breakdown components of whole and lysed blood. Mannitol permeability was up to four times higher in biliverdin treatments than controls, and arachnoid membranes demonstrated significantly decreased small molecule permeabilities in the presence of whole and lysed blood. We conclude that short-term (<24 h) arachnoid cell transport and long-term (>5 days) arachnoid cell viability are affected by blood and blood breakdown products, with important consequences for CSF flow and blood clearance after TBI.
authors.affiliation: Department of Research, Minneapolis VA Medical Center, 1 Veterans Drive, Research Service 151, Minneapolis, MN, 55417, USA. hanse989@umn.edu.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Hansen
authors.affiliation: Department of Research, Minneapolis VA Medical Center, 1 Veterans Drive, Research Service 151, Minneapolis, MN, 55417, USA.|Department of Neurology and Rehabilitation, University of Illinois, Chicago, IL, USA.
authors.forename: Liudmila
authors.initials: L
authors.lastname: Romanova
authors.affiliation: Department of Neurology and Rehabilitation, University of Illinois, Chicago, IL, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Janson
authors.affiliation: Department of Research, Minneapolis VA Medical Center, 1 Veterans Drive, Research Service 151, Minneapolis, MN, 55417, USA.|Department of Neurosurgery, Minneapolis VA Medical Center, Minneapolis, MN, USA.
authors.forename: Cornelius H
authors.initials: CH
authors.lastname: Lam
mesh_terms: D000818:Animals; D017209:Apoptosis; D001099:Arachnoid / Q000166:cytology* / Q000378:metabolism*; D001663:Bilirubin / Q000378:metabolism*; D001664:Biliverdine / Q000378:metabolism*; D001693:Biological Transport, Active / Q000502:physiology*; D001769:Blood / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000378:metabolism*; D000070642:Brain Injuries, Traumatic / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D004234:Diuretics, Osmotic / Q000493:pharmacokinetics; D004912:Erythrocytes / Q000378:metabolism*; D008297:Male; D008353:Mannitol / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000378:metabolism*; D013997:Time Factors
chemical_list: D004234:Diuretics, Osmotic; D008353:Mannitol; D001664:Biliverdine; D001663:Bilirubin
keywords: Blood–brain barrier; Subarachnoid hemorrhage; Transporters; Traumatic brain injury