{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T21:23:23Z","timestamp":1791581003386,"version":"4.3.4"},"reference-count":55,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2004,9,1]],"date-time":"2004-09-01T00:00:00Z","timestamp":1093996800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurochemistry International"],"published-print":{"date-parts":[[2004,9]]},"DOI":"10.1016\/j.neuint.2003.11.006","type":"journal-article","created":{"date-parts":[[2004,1,27]],"date-time":"2004-01-27T10:23:12Z","timestamp":1075198992000},"page":"545-552","source":"Crossref","is-referenced-by-count":731,"title":["Evidence for bulk flow of brain interstitial fluid: significance for physiology and pathology"],"prefix":"10.1016","volume":"45","author":[{"given":"N.Joan","family":"Abbott","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.neuint.2003.11.006_BIB1","doi-asserted-by":"crossref","unstructured":"Abbott, N.J., 1992. Comparative physiology of the blood\u2013brain barrier. In: Bradbury, M.W.B. (Ed.), Physiology and Pharmacology of the Blood\u2013Brain Barrier. Springer, Berlin, pp. 371\u2013396.","DOI":"10.1007\/978-3-642-76894-1_15"},{"key":"10.1016\/j.neuint.2003.11.006_BIB2","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1023\/A:1007074420772","article-title":"Inflammatory mediators and modulation of blood\u2013brain barrier permeability","volume":"20","author":"Abbott","year":"2000","journal-title":"Cell Mol. Neurobiol."},{"key":"10.1016\/j.neuint.2003.11.006_BIB3","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1046\/j.1469-7580.2002.00064.x","article-title":"Astrocyte-endothelial interactions and blood\u2013brain barrier permeability","volume":"200","author":"Abbott","year":"2002","journal-title":"J. Anat."},{"key":"10.1016\/j.neuint.2003.11.006_BIB4","unstructured":"Abbott, N.J., 2003. Dynamics of CNS barriers: evolution, differentiation and modulation. Cell Mol. Neurobiol., in press."},{"key":"10.1016\/j.neuint.2003.11.006_BIB5","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1113\/jphysiol.1985.sp015854","article-title":"Tightness of the blood\u2013brain barrier and evidence for brain interstitial fluid flow in the cuttlefish, Sepia officinalis","volume":"368","author":"Abbott","year":"1985","journal-title":"J. Physiol. (London)"},{"key":"10.1016\/j.neuint.2003.11.006_BIB6","first-page":"385","article-title":"Focal cerebral edema impedes convective fluid tracer movement through perivascular pathways in cat brain","volume":"52","author":"Blaumanis","year":"1990","journal-title":"Adv. Neurol."},{"key":"10.1016\/j.neuint.2003.11.006_BIB7","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1073\/pnas.91.6.2076","article-title":"Convection-enhanced delivery of macromolecules in the brain","volume":"91","author":"Bobo","year":"1994","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1016\/j.neuint.2003.11.006_BIB8","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1113\/jphysiol.1983.sp014731","article-title":"Factors influencing exit of substances from cerebrospinal fluid into deep cervical lymph of the rabbit","volume":"339","author":"Bradbury","year":"1983","journal-title":"J. Physiol. (London)"},{"key":"10.1016\/j.neuint.2003.11.006_BIB9","first-page":"329","article-title":"Drainage of cerebral interstitial fluid into deep cervical lymph of the rabbit","volume":"240","author":"Bradbury","year":"1981","journal-title":"Am. J. Physiol."},{"key":"10.1016\/j.neuint.2003.11.006_BIB10","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1002\/aja.1001170204","article-title":"The distribution within the brain of ferritin injected into cerebrospinal fluid compartments","volume":"117","author":"Brightman","year":"1965","journal-title":"Am. J. Anat."},{"key":"10.1016\/j.neuint.2003.11.006_BIB11","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1083\/jcb.40.3.648","article-title":"Junctions between intimately apposed cell membranes in the vertebrate brain","volume":"40","author":"Brightman","year":"1969","journal-title":"J. Cell Biol."},{"key":"10.1016\/j.neuint.2003.11.006_BIB12","doi-asserted-by":"crossref","unstructured":"Brosnan, C.F., Claudio, L., 1998. Brain microvasculature in multiple sclerosis. In: Pardridge, W.M. (Ed.), Introduction to the Blood\u2013Brain Barrier. Methodology, Biology and Pathology. Cambridge University Press, Cambridge, UK, pp. 386\u2013400.","DOI":"10.1017\/CBO9780511570216.042"},{"key":"10.1016\/j.neuint.2003.11.006_BIB13","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/S1043-6618(03)00038-0","article-title":"Neural stem cells: a pharmacological tool for brain diseases?","volume":"47","author":"Conti","year":"2003","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.neuint.2003.11.006_BIB14","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1152\/physrev.1971.51.2.273","article-title":"Physiology of the choroid plexus","volume":"51","author":"Cserr","year":"1971","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.neuint.2003.11.006_BIB15","doi-asserted-by":"crossref","unstructured":"Cserr, H.F., Patlak, C.S., 1992. Secretion and bulk flow of interstitial fluid. In: Bradbury, M.W.B. (Ed.), Physiology and Pharmacology of the Blood\u2013Brain Barrier. Springer, Berlin, pp. 245\u2013261.","DOI":"10.1007\/978-3-642-76894-1_9"},{"key":"10.1016\/j.neuint.2003.11.006_BIB16","first-page":"319","article-title":"Efflux of radiolabeled polyethylene glycols and albumin from rat brain","volume":"240","author":"Cserr","year":"1981","journal-title":"Am. J. Physiol."},{"key":"10.1016\/j.neuint.2003.11.006_BIB17","unstructured":"Davson, H., 1956. Physiology of the Ocular and Cerebrospinal Fluids. Churchill, London."},{"key":"10.1016\/j.neuint.2003.11.006_BIB18","unstructured":"Davson, H., Segal, M.B., 1995. Physiology of the CSF and Blood\u2013Brain Barriers. CRC Press, Boca Raton, USA."},{"key":"10.1016\/j.neuint.2003.11.006_BIB19","unstructured":"Davson, H., Kleeman, C.R., Levin, E., 1963. The blood\u2013brain barrier. In: Hogben, A.M., Lindgren, P. (Eds.), Drugs and Membranes, vol. 4. Pergamon Press, Oxford, pp. 71\u201394."},{"key":"10.1016\/j.neuint.2003.11.006_BIB20","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1097\/00004647-199709000-00002","article-title":"Kinetic modeling of [11C]raclopride: combined PET-microdialysis studies","volume":"17","author":"Endres","year":"1997","journal-title":"J. Cereb. Blood Flow Metabol."},{"key":"10.1016\/j.neuint.2003.11.006_BIB21","doi-asserted-by":"crossref","unstructured":"Fenstermacher, J.D., Patlak, C.S., 1976. The movements of water and solutes in the brains of mammals. In: Pappius, H.M., Feindel, E. (Eds.), Dynamics of Brain Edema. Springer, Berlin, pp. 87\u201394.","DOI":"10.1007\/978-3-642-66524-0_16"},{"key":"10.1016\/j.neuint.2003.11.006_BIB22","first-page":"2070","article-title":"Transport of material between brain extracellular fluid, brain cells and blood","volume":"33","author":"Fenstermacher","year":"1974","journal-title":"Federation Proc."},{"key":"10.1016\/j.neuint.2003.11.006_BIB23","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1023\/A:1005761031077","article-title":"Interstitial fluid flow along white matter tracts: a potentially important mechanism for the dissemination of primary brain tumours","volume":"32","author":"Geer","year":"1997","journal-title":"J. Neuro-Oncol."},{"key":"10.1016\/j.neuint.2003.11.006_BIB24","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1016\/0306-4522(96)00281-3","article-title":"Rapid distribution of intraventricularly administered sucrose into cerebrospinal fluid cisterns via subarachnoid velae in rat","volume":"75","author":"Ghersi-Egea","year":"1996","journal-title":"Neuroscience"},{"key":"10.1016\/j.neuint.2003.11.006_BIB25","first-page":"127","article-title":"\u00dcber ein perivascul\u00e4res Kanalsystem in den nerv\u00f6sen Central-Organen und \u00fcber dessen Beziehungen zum Lymphsystem","volume":"15","author":"His","year":"1865","journal-title":"Zeitschrift f\u00fcr Wissenschaft Zoologie"},{"key":"10.1016\/j.neuint.2003.11.006_BIB26","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/0006-8993(91)91275-6","article-title":"Distribution of extracellular tracers in perivascular spaces of the rat brain","volume":"545","author":"Ichimura","year":"1991","journal-title":"Brain Res."},{"key":"10.1016\/j.neuint.2003.11.006_BIB27","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/0165-3806(90)90163-S","article-title":"A morphometric study on the development of the lateral ventricle choroid plexus, choroid plexus capillaries and ventricular ependyma in the rat","volume":"56","author":"Keep","year":"1990","journal-title":"Dev. Brain Res."},{"key":"10.1016\/j.neuint.2003.11.006_BIB28","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1111\/j.1365-2990.1995.tb01048.x","article-title":"Anatomical pathways for lymphatic drainage of the brain and their pathological significance","volume":"21","author":"Kida","year":"1995","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"10.1016\/j.neuint.2003.11.006_BIB29","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S0304-3940(00)01705-5","article-title":"Aquaporin subtypes in rat cerebral microvessels","volume":"297","author":"Kobayashi","year":"2001","journal-title":"Neurosci. Lett."},{"key":"10.1016\/j.neuint.2003.11.006_BIB30","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S0959-4388(03)00017-5","article-title":"Neurogenesis after ischaemic brain insults","volume":"13","author":"Kokaia","year":"2003","journal-title":"Curr. Opin. Neurobiol."},{"key":"10.1016\/j.neuint.2003.11.006_BIB31","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/S0306-4522(00)00403-6","article-title":"Diffusion and action of intracerebroventricularly injected interleukin-1 in the CNS","volume":"101","author":"Konsman","year":"2000","journal-title":"Neuroscience"},{"key":"10.1016\/j.neuint.2003.11.006_BIB32","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1046\/j.1471-4159.2001.00113.x","article-title":"\u03b2-amyloid efflux mediated by p-glycoprotein","volume":"76","author":"Lam","year":"2001","journal-title":"J. Neurochem."},{"key":"10.1016\/j.neuint.2003.11.006_BIB33","doi-asserted-by":"crossref","first-page":"586","DOI":"10.3171\/jns.1997.87.4.0586","article-title":"Chronic interstitial infusion of protein to primate brain: determination of drug distribution and clearance with single-photon emission computerized tomography imaging","volume":"87","author":"Laske","year":"1997","journal-title":"J. Neurosurg."},{"key":"10.1016\/j.neuint.2003.11.006_BIB34","unstructured":"Mihaylov, I.R., Batchelor, P., Naghibi, M., Abbott, N.J., 2002. Quantitative evidence for production and convective flow of brain interstitial fluid, J. Physiol., 539P, 90P."},{"key":"10.1016\/j.neuint.2003.11.006_BIB35","first-page":"R292","article-title":"High-flow microinfusion: tissue penetration and pharmacodynamics","volume":"266","author":"Morrison","year":"1994","journal-title":"Am. J. Physiol."},{"key":"10.1016\/j.neuint.2003.11.006_BIB36","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/0006-8993(85)91586-0","article-title":"Diffusion from an injected volume of a substance in brain tissue with arbitrary volume fraction and tortuosity","volume":"333","author":"Nicholson","year":"1985","journal-title":"Brain Res."},{"key":"10.1016\/j.neuint.2003.11.006_BIB37","doi-asserted-by":"crossref","first-page":"387","DOI":"10.3171\/jns.1992.77.3.0387","article-title":"Clearance of brain edema and macromolecules through cortical extracellular space","volume":"77","author":"Ohata","year":"1992","journal-title":"J. Neurosurg."},{"key":"10.1016\/j.neuint.2003.11.006_BIB38","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/S0306-4522(99)00417-0","article-title":"Studies of cerebrospinal fluid flow and penetration into brain following lateral ventricle and cisterna magna injections of the tracer [14C]inulin in rat","volume":"95","author":"Proescholdt","year":"2000","journal-title":"Neuroscience"},{"key":"10.1016\/j.neuint.2003.11.006_BIB39","first-page":"2521","article-title":"Pressure dependent penetration of CSF into brain","volume":"43","author":"Pullen","year":"1984","journal-title":"Federation Proc."},{"key":"10.1016\/j.neuint.2003.11.006_BIB40","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/S0079-6123(08)64154-0","article-title":"Transport through the ependymal linings","volume":"29","author":"Rall","year":"1968","journal-title":"Prog. Brain Res."},{"key":"10.1016\/j.neuint.2003.11.006_BIB41","unstructured":"Rapoport, S.I., 1976. Blood\u2013brain Barrier in Physiology and Medicine. Raven Press, New York."},{"key":"10.1016\/j.neuint.2003.11.006_BIB42","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/0006-8993(85)91383-6","article-title":"Evidence for a \u201cparavascular\u201d fluid circulation in the mammalian central nervous system, provided by the rapid distribution of tracer protein throughout the brain from the subarachnoid space","volume":"326","author":"Rennels","year":"1985","journal-title":"Brain Res."},{"key":"10.1016\/j.neuint.2003.11.006_BIB43","first-page":"431","article-title":"Rapid solute transport throughout the brain via paravascular fluid pathways","volume":"52","author":"Rennels","year":"1990","journal-title":"Adv. Neurol."},{"key":"10.1016\/j.neuint.2003.11.006_BIB44","first-page":"42","article-title":"Bulk flow of brain interstitial fluid under normal and hyperosmolar conditions","volume":"238","author":"Rosenberg","year":"1980","journal-title":"Am. J. Physiol."},{"key":"10.1016\/j.neuint.2003.11.006_BIB45","doi-asserted-by":"crossref","unstructured":"Segal, M.B., Zlokovic, B.V., 1990. The Blood\u2013brain Barrier, Amino Acids and Peptides. Kluwer Academic Publishers, Dordrecht, Boston and London.","DOI":"10.1007\/978-94-009-2229-7"},{"key":"10.1016\/j.neuint.2003.11.006_BIB46","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1172\/JCI10498","article-title":"Clearance of Alzheimer\u2019s amyloid-\u03b21\u201340 peptide from brain by LDL receptor-related protein-1 at the blood\u2013brain barrier","volume":"106","author":"Shibata","year":"2000","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.neuint.2003.11.006_BIB47","doi-asserted-by":"crossref","unstructured":"Shielke, G.P., Betz, A.L., 1992. Electrolyte transport. In: Bradbury, M.W.B. (Ed.), Physiology and Pharmacology of the Blood\u2013brain Barrier. Springer, Berlin, pp. 221\u2013243.","DOI":"10.1007\/978-3-642-76894-1_8"},{"key":"10.1016\/j.neuint.2003.11.006_BIB48","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1046\/j.1469-7580.2002.00058.x","article-title":"Aquaporin channels and endothelial cell function","volume":"200","author":"Verkman","year":"2002","journal-title":"J. Anat."},{"key":"10.1016\/j.neuint.2003.11.006_BIB49","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1046\/j.0953-816x.2001.01643.x","article-title":"Astrocytes down-regulate neuronal \u03b2-amyloid precursor protein expression and modify its processing in an apolipoprotein E isoformspecific manner","volume":"14","author":"Vincent","year":"2001","journal-title":"Eur. J. Neurosci."},{"key":"10.1016\/j.neuint.2003.11.006_BIB50","first-page":"51","article-title":"The pathways of escape from the subarachnoid spaces with particular reference to the arachnoid villi","volume":"31","author":"Weed","year":"1914","journal-title":"J. Med. Res."},{"key":"10.1016\/j.neuint.2003.11.006_BIB51","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1111\/j.1750-3639.1992.tb00704.x","article-title":"Pathways of fluid drainage from the brain-morphological aspects and immunological significance in rat and man","volume":"2","author":"Weller","year":"1992","journal-title":"Brain Pathol."},{"key":"10.1016\/j.neuint.2003.11.006_BIB52","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1097\/00005072-199810000-00001","article-title":"Pathology of cerebrospinal fluid and interstitial fluid of the CNS: Significance for Alzheimer\u2019s disease, prion disorders and multiple sclerosis","volume":"57","author":"Weller","year":"1998","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"10.1016\/j.neuint.2003.11.006_BIB53","first-page":"115","article-title":"Convective delivery of macromolecules into the na\u0131\u0308ve and traumatized spinal cords of rats","volume":"90","author":"Wood","year":"1999","journal-title":"J. Neurosurg."},{"key":"10.1016\/j.neuint.2003.11.006_BIB54","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1111\/j.1469-185X.1954.tb00597.x","article-title":"Perivascular spaces of the mammalian central nervous system","volume":"29","author":"Woollam","year":"1954","journal-title":"Biol. Rev."},{"key":"10.1016\/j.neuint.2003.11.006_BIB55","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/BF00296784","article-title":"Directional and compartmentalised drainage of interstitial fluid and cerebrospinal fluid from the rat brain","volume":"83","author":"Zhang","year":"1992","journal-title":"Acta Neuropathol."}],"container-title":["Neurochemistry International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0197018603002675?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0197018603002675?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2020,3,29]],"date-time":"2020-03-29T10:35:23Z","timestamp":1585478123000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0197018603002675"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,9]]},"references-count":55,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2004,9]]}},"alternative-id":["S0197018603002675"],"URL":"https:\/\/doi.org\/10.1016\/j.neuint.2003.11.006","relation":{},"ISSN":["0197-0186"],"issn-type":[{"value":"0197-0186","type":"print"}],"subject":[],"published":{"date-parts":[[2004,9]]}}}