Pharmaceutical Research

, Volume 22, Issue 7, pp 1011–1037

Enhanced Prospects for Drug Delivery and Brain Targeting by the Choroid Plexus–CSF Route

  • Conrad E. Johanson
  • John A. Duncan
  • Edward G. Stopa
  • Andrew Baird
Expert Review

The choroid plexus (CP), i.e., the blood–cerebrospinal fluid barrier (BCSFB) interface, is an epithelial boundary exploitable for drug delivery to brain. Agents transported from blood to lateral ventricles are convected by CSF volume transmission (bulk flow) to many periventricular targets. These include the caudate, hippocampus, specialized circumventricular organs, hypothalamus, and the downstream pia–glia and arachnoid membranes. The CSF circulatory system normally provides micronutrients, neurotrophins, hormones, neuropeptides, and growth factors extensively to neuronal networks. Therefore, drugs directed to CSF can modulate a variety of endocrine, immunologic, and behavioral phenomema; and can help to restore brain interstitial and cellular homeostasis disrupted by disease and trauma. This review integrates information from animal models that demonstrates marked physiologic effects of substances introduced into the ventricular system. It also recapitulates how pharmacologic agents administered into the CSF system prevent disease or enhance the brain’s ability to recover from chemical and physical insults. In regard to drug distribution in the CNS, the BCSFB interaction with the blood–brain barrier is discussed. With a view toward translational CSF pharmacotherapy, there are several promising innovations in progress: bone marrow cell infusions, CP encapsulation and transplants, neural stem cell augmentation, phage display of peptide ligands for CP epithelium, CSF gene transfer, regulation of leukocyte and cytokine trafficking at the BCSFB, and the purification of neurotoxic CSF in degenerative states. The progressively increasing pharmacological significance of the CP–CSF nexus is analyzed in light of treating AIDS, multiple sclerosis, stroke, hydrocephalus, and Alzheimer’s disease.

Key Words

blood–CSF barrier brain drug delivery cerebrospinal fluid choroid plexus CSF bulk flow CSF pharmacokinetics intracerebroventricular volume transmission 

References

  1. 1.
    Johanson, C. E. 1988

    The choroid plexus–arachnoid–cerebrospinal fluid system

    Boulton, A.Baker, G.Walz, W. eds. Neuromethods, Vol. 9, Neuronal Microenvironment—Electrolytes and Water SpacesHumana PressClifton, NJ33104
    Google Scholar
  2. 2.
    Ghersi-Egea, J. F., Leininger-Muller, B., Cecchelli, R., Fenstermacher, J. D. 1995Blood–brain interfaces: relevance to cerebral drug metabolismToxicol. Lett.82–83645653Google Scholar
  3. 3.
    C. E. Johanson. Arachnoid membrane, subarachnoid CSF and pia–glia. In W. Pardridge (ed.), An Introduction to the Blood–Brain Barrier: Methodology and Biology, Cambridge University Press, Cambridge, 1998, pp. 259–269.Google Scholar
  4. 4.
    Smith, Q. R. 1989

    Quantitation of blood–brain barrier permeability

    Neuwelt, E. eds. Implications of the Blood–Brain Barrier and Its Manipulation, Vol. 1: Basic Sci. Aspects,, Plenum PressNew York85118
    Google Scholar
  5. 5.
    Graff, C. L., Pollack, G. M. 2004Drug transport at the blood–brain barrier and the choroid plexusCurr. Drug Metab.595108Google Scholar
  6. 6.
    Johanson, C. E. 1989

    Potential for pharmacological manipulation of the blood–CSF barrier

    Neuwelt, E. eds. Implications of the Blood–Brain Barrier and Its Manipulation, Vol. 1: Basic Science AspectsPlenum PressNew York223260
    Google Scholar
  7. 7.
    Pardridge, W. M., Frank, H. J. L., Cornford, E. M., Braun, L. D., Crane, P. D., Oldendorf, W. H. 1981

    Neuropeptides and the blood–brain barrier

    Martin, J.Reichlin, S.Bick, K. eds. Neurosecretion and Brain PeptidesRaven PressNew York321328
    Google Scholar
  8. 8.
    W. M. Pardridge. Receptor-mediated transport of peptides through the blood–brain barrier. In B. Johansson, C. Owman, and H. Widner (eds.), Pathophysiology of the Blood–Brain Barrier, Elsevier, Amsterdam, 1990, pp. 61–69.Google Scholar
  9. 9.
    Faraci, F. M., Kinzenbaw, D., Heistad, D. D. 1994Effect of endogenous vasopressin on blood flow to choroid plexus during hypoxoia and intracranial hypertensionAm. J. Physiol.266H393H398Google Scholar
  10. 10.
    Szmydynger-Chodobska, J., Chodobski, A., Johanson, C. E. 1994Postnatal developmental changes in blood flow to choroid plexuses and cerebral cortex of the ratAm. J. Physiol266R1488R1492Google Scholar
  11. 11.
    Keep, R. F., Jones, H. C. 1990A morphometric study on the development of the lateral ventricle choroid plexus, choroid plexus capillaries and ventricular ependyma in the ratBrain. Res. Dev. Brain. Res.564753Google Scholar
  12. 12.
    Johanson, C. E., Preston, J. E., Chodobski, A., Stopa, E. G., Szmydynger-Chodobska, J., McMillan, P. N. 1999AVP V1 receptor-mediated decrease in Cl efflux and increase in dark cell number in choroid plexus epitheliumAm. J. Physiol.276C82C90Google Scholar
  13. 13.
    Smith, Q. R., Johanson, C. E., Woodbury, D. M. 1981Uptake of36Cl and 22Na by the brain–cerebrospinal fluid system: comparison of the permeability of the blood–brain and blood–cerebrospinal fluid barriersJ. Neurochem.37117124Google Scholar
  14. 14.
    Huber, J. D., Egleton, R. D., Davis, T. P. 2001Molecular physiology and pathophysiology of tight junctions in the blood–brain barrierTrends Neurosci.24719725Google Scholar
  15. 15.
    Thomas, S. A., Segal, M. B. 1998The transport of the anti-HIV drug, 2′,3′-didehydro-3′-deoxythymidine (D4T), across the blood–brain and blood–cerebrospinal fluid barriersBr. J. Pharmacol.1254954Google Scholar
  16. 16.
    Johanson, C. E. 1980Permeability and vascularity of the developing brain: cerebellum vs. cerebral cortexBrain Res.190316Google Scholar
  17. 17.
    Murphy, V. A., Johanson, C. E. 1985Adrenergic-induced enhancement of brain barrier system permeability to small nonelectrolytes: choroid plexus versus cerebral capillariesJ. Cereb. Blood Flow Metab5401412Google Scholar
  18. 18.
    Johanson, C. E., Woodbury, D. M. 1978Uptake of (14C)urea bythe in vivo choroid plexus–cerebrospinal fluid–brain system: identification of sites of molecular sievingJ. Physiol.275167176Google Scholar
  19. 19.
    Parandoosh, Z., Johanson, C. E. 1982Ontogeny of blood–brain barrier permeability to, and cerebrospinal fluid sink action on, (14C)ureaAm. J. Physiol.243R400R407Google Scholar
  20. 20.
    Johanson, C. E., Foltz, F. M., Thompson, A. M. 1974The clearance of urea and sucrose from isotonic and hypertonic fluids perfused through the ventriculo-cisternal systemExp. Brain Res.201831Google Scholar
  21. 21.
    Bouchaud, C., Bouvier, D. 1978Fine structure of tight junctions between rat choroidal cells after osmotic opening induced by urea and sucroseTissue Cell10331342Google Scholar
  22. 22.
    Doolittle, N. D., Miner, M. E., Hall, W. A., Siegal, T., Jerome, E., Osztie, E., McAllister, L. D., Bubalo, J. S., Kraemer, D. F., Fortin, D., Nixon, R., Muldoon, L. L., Neuwelt, E. A. 2000Safety and efficacy of a multicenter study using intraarterial chemotherapy in conjunction with osmotic opening of the blood–brain barrier for the treatment of patients with malignant brain tumorsCancer88637647Google Scholar
  23. 23.
    Murphy, V. A., Johanson, C. E. 1989Acidosis, acetazolamide, and amiloride: effects on 22Na transfer across the blood–brain and blood–CSF barriersJ. Neurochem.5210581063Google Scholar
  24. 24.
    Angelow, S., Haselbach, M., Galla, H. J. 2003Functional characterization of the active ascorbic acid transport into cerebrospinal fluid using primary cultured choroid plexus cellsBrain Res.988105113Google Scholar
  25. 25.
    Rice, M. E. 2000Ascorbate regulation and its neuroprotective role in the brainTrends Neurosci.23209216Google Scholar
  26. 26.
    Bakowska, J. C., Morrell, J. I. 2003The distribution of mRNA for the short form of the prolactin receptor in the forebrain of the female ratBrain Res. Mol. Brain Res.1165058Google Scholar
  27. 27.
    Spector, R., Johanson, C. E. 1989The mammalian choroid plexusSci. Am.2616874Google Scholar
  28. 28.
    Rice, M. E. 1999Ascorbate compartmentalization in the CNSNeurotox. Res.28190Google Scholar
  29. 29.
    D. E. Smith, C. E. Johanson, and R. F. Keep. Peptide and peptide analog transport systems at the blood–CSF barrier. In Y. Sugiyama and J.-F., and Ghersi-Egea (eds.), Drug Transfer in the Choroid Plexus. Multiplicities and Substrate Specificities of Transporters. Adv. Drug Deliv. Rev. 56:1765–1791 (2004).Google Scholar
  30. 30.
    Tu, G. F., Cole, T., Southwell, B. R., Schreiber, G. 1990Expression of the genes for transthyretin, cystatin C and beta A4 amyloid precursor protein in sheep choroid plexus during developmentBrain Res. Dev. Brain Res.55203208Google Scholar
  31. 31.
    Li, M. D., Kane, J. K., Matta, S. G., Blaner, W. S., Sharp, B. M. 2000Nicotine enhances the biosynthesis and secretion of transthyretin from the choroid plexus in rats: implications for beta-amyloid formationJ. Neurosci.2013181323Google Scholar
  32. 32.
    C. E. Johanson, G. D. Silverberg, J. E. Donahue, J. A. Duncan, E. G. Stopa. Choroid plexus and CSF in Alzheimer’s Disease: altered expression and transport of proteins and peptides. In W. Zheng and A. Chodobski (eds.), The Blood–Cerebrospinal Fluid Barrier, CRC Press, Boca Raton, FL, 2005, pp. 307–339.Google Scholar
  33. 33.
    Bradbury, M. W., Cole, D. F. 1980The role of the lymphatic system in drainage of cerebrospinal fluid and aqueous humourJ. Physiol.299353365Google Scholar
  34. 34.
    Boulton, M., Flessner, M., Armstrong, D., Mohamed, R., Hay, J., Johnston, M. 1999Contribution of extracranial lymphatics and arachnoid villi to the clearance of a CSF tracer in the ratAm. J. Physiol.276R818R823Google Scholar
  35. 35.
    Rennels, M. L., Gregory, T. F., Blaumanis, O. R., Fujimoto, K., Grady, P. A. 1985Evidence for a ‘paravascular’ fluid circulation in the mammalian central nervous system, provided by the rapid distribution of tracer protein throughout the brain from the subarachnoid spaceBrain Res.3264763Google Scholar
  36. 36.
    Rennels, M. L., Blaumanis, O. R., Grady, P. A. 1990Rapid solute transport throughout the brain via paravascular fluid pathwaysAdv. Neurol.52431439Google Scholar
  37. 37.
    Proescholdt, M. G., Hutto, B., Brady, L. S., Herkenham, M. 2000Studies of cerebrospinal fluid flow and penetration into brain following lateral ventricle and cisterna magna injections of the tracer [14C]inulin in ratNeuroscience95577592Google Scholar
  38. 38.
    C. Johanson. The choroid plexus–CSF nexus: gateway to the brain. In P. Michael Conn (ed.), Neuroscience in Medicine, Humana Press, Totowa, NJ, 2003, pp. 165–195.Google Scholar
  39. 39.
    C. E. Johanson. Choroid plexus and volume transmission. In G. Adelman (ed.), Encyclopedia for Neuroscience, Vol. I, Birkhauser, Boston, electronic edition, 2004.Google Scholar
  40. 40.
    Fenstermacher, J. D., Ghersi-Egea, J. F., Finnegan, W., Chen, J. L. 1997The rapid flow of cerebrospinal fluid from ventricles to cisterns via subarachnoid velae in the normal ratActa Neurochir., Suppl. (Wien)70285287Google Scholar
  41. 41.
    Gozzi, A., Schwarz, A. J., Reese, T., Crestan, V., Bertani, S., Turrini, G., Corsi, M., Bifone, A. 2005Functional magnetic resonance mapping of intracerebroventricular infusion of a neuroactive peptide in the anaesthetised ratJ. Neurosci. Methods142115124Google Scholar
  42. 42.
    Huang, E., Ong, W. Y. 2005Distribution of ferritin in the rat hippocampus after kainate-induced neuronal injuryExp. Brain Res.161502511Google Scholar
  43. 43.
    Edagawa, Y., Sato, F., Saito, H., Takeda, T., Shimizu, N., Narui, T., Shibata, S., Ito, Y. 2005Dual effects of the lichen glucan PB-2, extracted from Flavoparmelia baltimorensis, on the induction of long-term potentiation in the dentate gyrus of the anesthetized rat: possible mediation via adrenaline beta- and interleukin-1 receptorsBrain Res.1032183192Google Scholar
  44. 44.
    Zhu, C. Z., Hsieh, G., Ei-Kouhen, O., Wilson, S. G., Mikusa, J. P., Hollingsworth, P. R., Chang, R., Moreland, R. B., Brioni, J., Decker, M.W., Honore, P. 2005Role of central and peripheral mGluR5 receptors in post-operative pain in ratsPain114195202Google Scholar
  45. 45.
    Zubrzycka, M., Fichna, J., Janecka, A. 2005Inhibition of trigemino-hypoglossal reflex in rats by oxytocin is mediated by mu and kappa opioid receptorsBrain Res.10356772Google Scholar
  46. 46.
    Kimura, T., Shimizu, T., Funahashi, T., Nagakura, M., Watanabe, K., Tachibana, K., Kondo, S., Ho, I. K., Yamamoto, I. 2003N3-phenacyluridine as a new type of antinociceptive compound in miceRes. Commun. Mol. Pathol. Pharmacol.113–1145765Google Scholar
  47. 47.
    Schmidt, A. P., Avila, T. T., Souza, D. O. 2005Intracerebroventricular guanine-based purines protect against seizures induced by quinolinic acid in miceNeurochem. Res.306973Google Scholar
  48. 48.
    Kudina, T. A., Sudnitsyn, V. V., Kutyreva, E. V., Kichigina, V. F. 2004The serotonin reuptake inhibitor fluoxetine suppresses theta oscillations in the electroencephalogram of the rabbit hippocampusNeurosci. Behav. Physiol.34929933Google Scholar
  49. 49.
    Semba, K., Adachi, N., Arai, T. 2005Facilitation of serotonergic activity and amnesia in rats caused by intravenous anestheticsAnesthesiology102616623Google Scholar
  50. 50.
    Tajima, H., Kawasumi, M., Chiba, T., Yamada, M., Yamashita, K., Nawa, M., Kita, Y., Kouyama, K., Aiso, S., Matsuoka, M., Niikura, T., Nishimoto, I. 2005A humanin derivative, S14G-HN, prevents amyloid-beta-induced memory impairment in miceJ. Neurosci. Res.79714723Google Scholar
  51. 51.
    Ramirez, B. G., Blazquez, C., Gomez del Pulgar, T., Guzman, M., Ceballos, M. L. 2005Prevention of Alzheimer’s disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activationJ. Neurosci.2519041913Google Scholar
  52. 52.
    Chauhan, N. B., Siegel, G. J. 2005Efficacy of anti-Abeta antibody isotypes used for intracerebroventricular immunization in TgCRND8Neurosci. Lett.375143147Google Scholar
  53. 53.
    Arjona, A. A., Pooler, A. M., Lee, R. K., Wurtman, R. J. 2002Effect of a 5-HT(2C) serotonin agonist, dexnorfenfluramine, on amyloid precursor protein metabolism in guinea pigsBrain Res.951135140Google Scholar
  54. 54.
    Banasr, M., Hery, M., Printemps, R., Daszuta, A. 2004Serotonin-induced increases in adult cell proliferation and neurogenesis are mediated through different and common 5-HT receptor subtypes in the dentate gyrus and the subventricular zoneNeuropsychopharmacology29450460Google Scholar
  55. 55.
    Pritchard, J. B., Sweet, D. H., Miller, D. S., Walden, R. 1999Mechanism of organic anion transport across the apical membraneof choroid plexusJ. Biol. Chem.2743338233387Google Scholar
  56. 56.
    Hayamizu, T. F., Chan, P. T., Johanson, C. E. 2001FGF2 immunoreactivity in adult rat ependyma and choroid plexus: responses to global forebrain ischemia and intraventricular FGF2Neurol. Res.23353358Google Scholar
  57. 57.
    Rosenberg, G. A., Kyner, W. T., Fenstermacher, J. D., Patlak, C. S. 1986Effect of vasopressin on ependymal and capillary permeability to tritiated water in catAm. J. Physiol.251F485F489Google Scholar
  58. 58.
    Kuchler-Bopp, S., Ittel, M. E., Dietrich, J. B., Reeber, A., Zaepfel, M., Delaunoy, J. P. 1998The presence of transthyretin in rat ependymal cells is due to endocytosis and not synthesisBrain Res.793219230Google Scholar
  59. 59.
    Gard, A. L., Gavin, E., Solodushko, V., Pennica, D. 2004Cardiotrophin-1 in choroid plexus and the cerebrospinal fluid circulatory systemNeuroscience1274352Google Scholar
  60. 60.
    Graff, M. N., Baas, D., Puymirat, J., Sarlieve, L. L., Delaunoy, J. P. 1993The alpha and beta thyroid receptors are expressed by cultured ependymal cells. Correlation with the effect of l-3,5,3′-triiodothyronine on glutamine synthetase mRNAsNeuroscience150174178Google Scholar
  61. 61.
    Yang, G. Y., Zhao, Y. J., Davidson, B. L., Betz, A. L. 1997Overexpression of interleukin-receptor antagonist in the mouse brainreduces ischemic brain injuryBrain Res.751181188Google Scholar
  62. 62.
    Oomura, Y., Sasaki, K., Suzuki, K., Muto, T., Li, A. J., Ogita, Z., Hanai, K., Tooyama, I., Kimura, H., Yanaihara, N. 1992A new brain glucosensor and its physiological significanceAm. J. Clin. Nutr.55278S282SGoogle Scholar
  63. 63.
    Kimelberg, H. K., Kung, D., Watson, R. E., Reiss, F. L., Biddlecome, S. M., Bourke, R. S. 1978Direct administration of methotrexate into the central nervous system of primates: Part 1. Distribution and degradation of methotrexate in nervous and systemic tissue after intraventricular injectionJ. Neurosurg.48883894Google Scholar
  64. 64.
    Morikawa, N., Mori, T., Kawashima, H., Fujiki, M., Abe, T., Kaku, T., Konisi, Y., Takeyama, M., Hori, S. 1998Pharmacokinetics of nimustine, methotrexate, and cytosine arabinoside during cerebrospinal fluid perfusion chemotherapy in patients with disseminated brain tumorsEur. J. Clin. Pharmacol.54415420Google Scholar
  65. 65.
    Antunes, N. L., Souweidane, N. M., Lis, E., Rosenblum, M. K., Steinherz, P. G. 2002Methotrexate leukoencephalopathy presenting as Kluver–Bucy syndrome and uncinate seizuresPediatr. Neurol.26305308Google Scholar
  66. 66.
    Shapiro, W. R. 1975Chemotherapy of primary malignant brain tumors in childrenCancer35965972Google Scholar
  67. 67.
    Chamberlain, M. C., Kormanik, P. A., Barba, D. 1997Complications associated with intraventricular chemotherapy in patients with leptomeningeal metastasesJ. Neurosurg.87694699Google Scholar
  68. 68.
    Johanson, C. E., McMillan, P. N., Palm, D. E., Stopa, E. G., Doberstein, C. E., Duncan, J. A. 2004

    Volume transmission-mediated protective impact of choroid plexus–CSF growth factors onforebrain ischemic injury

    Sharma, H. S.Westman, J. eds. Blood–Spinal Cord and Brain Barriers in Health and DiseaseAcademic PressSan Diego361384
    Google Scholar
  69. 69.
    Mercer, A., Ronnholm, H., Holmberg, J., Lundh, H., Heidrich, J., Zachrisson, O., Ossoinak, A., Frisen, J., Patrone, C. 2004PACAP promotes neural stem cell proliferation in adult mouse brainJ. Neurosci. Res.76205215Google Scholar
  70. 70.
    Banks, W. A., Goulet, M., Rusche, J. R., Niehoff, M. L., Boismenu, R. 2002Differential transport of a secretin analog across the blood–brain and blood–cerebrospinal fluid barriers of the mouseJ. Pharmacol. Exp. Ther.30210621069Google Scholar
  71. 71.
    Miyan, J. A., Nabiyouni, M., Zendah, M. 2003Development of the brain: a vital role for cerebrospinal fluidCan. J. Physiol. Pharmacol.81317328Google Scholar
  72. 72.
    Mashayekhi, F., Draper, C. E., Bannister, C. M., Pourghasem, M., Owen-Lynch, P. J., Miyan, J. A. 2002Deficient cortical development in the hydrocephalic Texas (H-Tx) rat: a role for CSFBrain12518591874Google Scholar
  73. 73.
    Owen-Lynch, P. J., Draper, C. E., Mashayekhi, F., Bannister, C. M., Miyan, J. A. 2003Defective cell cycle control underlies abnormal cortical development in the hydrocephalic Texas ratBrain126623631Google Scholar
  74. 74.
    Liu, R. Y., Zhou, J. N., Heerikhuize, J., Hofman, M. A., Swaab, D. F. 1999Decreased melatonin levels in postmortem cerebrospinal fluid in relation to aging, Alzheimer’s disease, and apolipoprotein E-epsilon4/4 genotypeJ. Clin. Endocrinol. Metab.84323327Google Scholar
  75. 75.
    Somera, K. C., Jones, H. C. 2004Reduced subcommissural organ glycoprotein immunoreactivity precedes aqueduct closure and ventricular dilatation in H-Tx rat hydrocephalusCell Tissue Res.315361373Google Scholar
  76. 76.
    Rodriguez, E. M., Oksche, A., Montecinos, H. 2001Human subcommissural organ, with particular emphasis on its secretoryactivity during fetal lifeMicrosc. Res. Tech.52573590Google Scholar
  77. 77.
    Ghersi-Egea, J. F., Leninger-Muller, B., Suleman, G., Siest, G., Minn, A. 1994Localization of drug-metabolizing enzyme activities to blood–brain interface and circumventricular organsJ. Neurochem.6210891096Google Scholar
  78. 78.
    Ghersi-Egea, J. F., Strazielle, N. 2001Brain drug delivery, drug metabolism, and multidrug resistance at the choroid plexusMicrosc. Res. Tech.528388Google Scholar
  79. 79.
    Strazielle, N., Ghersi-Egea, J. F. 2000Choroid plexus in the central nervous system: biology and physiopathologyJ. Neuropathol. Exp. Neurol.59561574Google Scholar
  80. 80.
    Fenstermacher, J., Kaye, T. 1988Drug “diffusion” within the brainAnn. N. Y. Acad. Sci.5312939Google Scholar
  81. 81.
    Haar, P. J., Stewart, J. E., Gillies, G. T., Prabhu, S. S., Broaddus, W. C. 2001Quantitative three-dimensional analysis and diffusion modeling of oligonucleotide concentrations after direct intraparenchymal brain infusionIEEE Trans. Biomed. Eng.48560569Google Scholar
  82. 82.
    Blasberg, R. G., Patlak, C., Fenstermacher, J. D. 1975Intrathecal chemotherapy: brain tissue profiles after ventriculocisternal perfusionJ. Pharmacol. Exp. Ther.1957383Google Scholar
  83. 83.
    Kohler, C., Radesater, A. C., Karlsson-Boethius, G., Bryske, B., Widman, M. 1992Regional distribution and in vivo binding of the atypical antipsychotic drug remoxipride. A biochemical and autoradiographic analysis in the rat brainJ. Neural Transm. Gen. Sect.874962Google Scholar
  84. 84.
    Hammarstrom, L. 1966Autoradiographic studies on the distribution of C14-labelled ascorbic acid and dehydroascorbic acidActa Physiol. Scand.70184Google Scholar
  85. 85.
    Ley, G., Weyne, J., Demeester, G., Leusen, I. 1982Response of local blood flow in the caudate nucleus of the cat to intraventricular administration of histamineStroke13499504Google Scholar
  86. 86.
    Ley, G., Weyne, J., Demeester, G., Leusen, I. 1984Response of local blood flow in the caudate nucleus of the cat to intraventricular administration of carbacholStroke15481486Google Scholar
  87. 87.
    McPherson, R. W., Koehler, R. C., Kirsch, J. R., Traystman, R. J. 1997Intraventricular dexmedetomidine decreases cerebral blood flow during normoxia and hypoxia in dogsAnesth. Analg.84139147Google Scholar
  88. 88.
    Shimizu, S., Nagayama, T., Jin, K. L., Zhu, L., Loeffert, J. E., Watkins, S. C., Graham, S. H., Simon, R. P. 2001bcl-2 Antisense treatment prevents induction of tolerance to focal ischemia in the rat brainJ. Cereb. Blood Flow Metab.21233243Google Scholar
  89. 89.
    Yamada, S., Khankaldyyan, V., Bu, X., Suzuki, A., Gonzalez-Gomez, I., Takahashi, K., McComb, J. G., Laug, W. E. 2004A method to accurately inject tumor cells into the caudate/putamen nuclei of the mouse brainTokai J. Exp. Clin. Med.29167173Google Scholar
  90. 90.
    Frewert, S., Stockhammer, F., Warschewske, G., Zenclussen, A. C., Rupprecht, S., Volk, H. D., Woiciechowsky, C. 2004Intratumoral infusion of interleukin-1beta and interferon-gamma induces tumor invasion with macrophages and lymphocytes in a rat glioma modelNeurosci. Lett.364145148Google Scholar
  91. 91.
    Landy, H., Markoe, A., Potter, P., Lasalle, G., Marini, A., Savaraj, N., Reis, I., Heros, D., Wangpaichitr, M., Feun, L. 2004Pilot study of estramustine added to radiosurgery and radiotherapy for treatment of high grade gliomaJ. Neuro-oncol.67215220Google Scholar
  92. 92.
    Valerie, K., Hawkins, W., Farnsworth, J., Schmidt-Ullrich, R., Lin, P. S., Amir, C., Feden, J. 2001Substantially improved in vivo radiosensitization of rat glioma with mutant HSV-TK and acyclovirCancer Gene Ther.838Google Scholar
  93. 93.
    Deutsch, M., Rewers, A. B., Redgate, S., Fisher, E. R., Boggs, S. S. 1990Intra-cerebral ventricular infusion of 5-iodo-2-deoxyuridine (IUDR) as a radiosensitizer in the treatment of a rat gliomaInt. J. Radiat. Oncol. Biol. Phys.198587Google Scholar
  94. 94.
    Palm, D., Knuckey, N., Guglielmo, M., Watson, P., Primiano, M., Johanson, C. 1995Choroid plexus electrolytes and ultrastructure following transient forebrain ischemiaAm. J. Physiol.269R73R79Google Scholar
  95. 95.
    Ferrand-Drake, M., Wieloch, T. 1999The time-course of DNA fragmentation in the choroid plexus and the CA1 region following transient global ischemia in the rat brain. The effect of intra-ischemic hypothermiaNeuroscience93537549Google Scholar
  96. 96.
    Johanson, C. E., Palm, D. E., Primiano, M. J., McMillan, P. N., Chan, P., Knuckey, N. W., Stopa, E. G. 2000Choroid plexus recovery after transient forebrain ischemia: role of growth factors and other repair mechanismsCell Mol. Neurobiol.20197216Google Scholar
  97. 97.
    Knuckey, N. W., Finch, P., Palm, D. E., Primiano, M. J., Johanson, C. E., Flanders, K. C., Thompson, N. L. 1996Differential neuronal and astrocytic expression of transforming growth factor beta isoforms in rat hippocampus following transient forebrain ischemiaBrain Res. Mol. Brain Res.40114Google Scholar
  98. 98.
    Wen, T. C., Tanaka, J., Peng, H., Desaki, J., Matsuda, S., Maeda, N., Fujita, H., Sato, K., Sakanaka, M. 1998Interleukin 3 prevents delayed neuronal death in the hippocampal CA1 fieldJ. Exp. Med.188635649Google Scholar
  99. 99.
    Hu, X., Nesic-Taylor, O., Qiu, J., Rea, H. C., Fabian, R., Rassin, D. K., Perez-Polo, J. R. 2005Activation of nuclear factor-kappa B signaling pathway by interleukin-1 after hypoxia/ischemia in neonatal rat hippocampus and cortexJ. Neurochem.932637Google Scholar
  100. 100.
    Farkas, B., Tantos, A., Schlett, K., Vilagi, I., Friedrich, P. 2004Ischemia-induced increase in long-term potentiation is warded off by specific calpain inhibitor PD150606Brain Res.1024150158Google Scholar
  101. 101.
    Kawai, T., Takagi, N., Miyake-Takagi, K., Okuyama, N., Mochizuki, N., Takeo, S. 2004Characterization of BrdU-positive neurons induced by transient global ischemia in adult hippocampusJ. Cereb. Blood Flow Metab.24548555Google Scholar
  102. 102.
    Hashiguchi, A., Yano, S., Morioka, M., Hamada, J., Ushio, Y., Takeuchi, Y., Fukunaga, K. 2004Up-regulation of endothelial nitric oxide synthase via phosphatidylinositol 3-kinase pathway contributes to ischemic tolerance in the CA1 subfield of gerbil hippocampusJ. Cereb. Blood Flow Metab.24271279Google Scholar
  103. 103.
    Gulyaeva, N. V., Lazareva, N. A., Libe, M. L., Mitrokhina, O. S., Onufriev, M. V., Stepanichev, M. Y., Chernysevskaya, I. A., Walsh, T. J. 1996Oxidative stress in the brain following intraventricular administration of ethylcholine aziridinium (AF64A)Brain Res.726174180Google Scholar
  104. 104.
    Zujovic, V., Schussler, N., Jourdain, D., Duverger, D., Taupin, V. 2001In vivo neutralization of endogenous brain fractalkine increases hippocampal TNFalpha and 8-isoprostane production induced by intracerebroventricular injection of LPSJ. Neuroimmunol.115135143Google Scholar
  105. 105.
    Zlokovic, B. V., Jovanovic, S., Miao, W., Samara, S., Verma, S., Farrell, C. L. 2000Differential regulation of leptin transport by the choroid plexus and blood–brain barrier and high affinity transport systems for entry into hypothalamus and across the blood–cerebrospinal fluid barrierEndocrinology14114341441Google Scholar
  106. 106.
    Mangurian, L. P., Walsh, R. J., Posner, B. I. 1992Prolactin enhancement of its own uptake at the choroid plexusEndocrinology131698702Google Scholar
  107. 107.
    Bakowska, J. C., Morrell, J. I. 2003The distribution of mRNA for the short form of the prolactin receptor in the forebrain of the female ratBrain Res. Mol. Brain Res.1165058Google Scholar
  108. 108.
    Fujikawa, T., Soya, H., Tamashiro, K. L., Sakai, R. R., McEwen, B. S., Nakai, N., Ogata, M., Suzuki, I., Nakashima, K. 2004Prolactin prevents acute stress-induced hypocalcemia and ulcerogenesis by acting in the brain of ratEndocrinology14520062013Google Scholar
  109. 109.
    Chikanza, I. C. 1999Prolactin and neuroimmunomodulation: in vitro and in vivo observationsAnn. N.Y. Acad. Sci.876119130Google Scholar
  110. 110.
    Berger, U. V., Hediger, M. A. 2001Differential distribution of the glutamate transporters GLT-1 and GLAST in tanycytes of the third ventricleJ. Comp. Neurol.433101114Google Scholar
  111. 111.
    Peruzzo, B., Pastor, F. E., Blazquez, J. L., Amat, P., Rodriguez, E. M. 2004Polarized endocytosis and transcytosis in the hypothalamic tanycytes of the ratCell Tissue Res.317147164Google Scholar
  112. 112.
    Sarkar, S., Lechan, R. M. 2003Central administration of neuropeptide Y reduces alpha-melanocyte-stimulating hormone-induced cyclic adenosine 5′-monophosphate response element binding protein (CREB) phosphorylation in pro-thyrotropin-releasing hormone neurons and increases CREB phosphorylation in corticotropin-releasing hormone neurons in the hypothalamic paraventricular nucleusEndocrinology144281291Google Scholar
  113. 113.
    Huang, B. S., Wang, H., Leenen, F. H. 2001Enhanced sympathoexcitatory and pressor responses to central Na+ in Dahl salt-sensitive vs. -resistant ratsAm. J. Physiol.281H1881H1889Google Scholar
  114. 114.
    Rossi, N. F., Chen, H. 2001PVN lesions prevent the endothelin 1-induced increase in arterial pressure and vasopressinAm. J. Physiol.280E349E356Google Scholar
  115. 115.
    Muzzin, P., Cusin, I., Charnay, Y., Rohner-Jeanrenaud, F. 2000Single intracerebroventricular bolus injection of a recombinant adenovirus expressing leptin results in reduction of food intake and body weight in both lean and obese Zucker fa/fa ratsRegul. Pept.925764Google Scholar
  116. 116.
    Angelopoulos, N., Kallaras, C., Apostolakis, M. 1996Effects of intracerebroventricular administration of atrial natriuretic peptide on subcortical EEG activity in conscious rabbitsExp. Brain Res.108427432Google Scholar
  117. 117.
    McMinn, J. E., Seeley, R. J., Wilkinson, C. W., Havel, P. J., Woods, S. C., Schwartz, M. W. 1998NPY-induced overfeeding suppresses hypothalamic NPY mRNA expression: potential roles of plasma insulin and leptinRegul. Pept.75–76425431Google Scholar
  118. 118.
    Givalois, L., Naert, G., Rage, F., Ixart, G., Arancibia, S., Tapia-Arancibia, L. 2004A single brain-derived neurotrophic factor injection modifies hypothalamo–pituitary–adrenocortical axis activity in adult male ratsMol. Cell. Neurosci.27280295Google Scholar
  119. 119.
    Wojcik-Gladysz, A., Romanowicz, K., Misztal, T., Polkowska, J., Barcikowski, B. 2005Effects of intracerebroventricular infusion of genistein on the secretory activity of the GnRH/LH axis in ovariectomized ewesAnim. Reprod. Sci.86221235Google Scholar
  120. 120.
    Shigemoto, Y., Fujii, Y., Shinomiya, K., Kamei, C. 2004Participation of histaminergic H1 and noradrenergic alpha 1 receptors in orexin A-induced wakefulness in ratsBrain Res.1023121125Google Scholar
  121. 121.
    Tsushima, H., Mori, M. 2005Mechanisms underlying anorexia after microinjection of bombesin into the lateral cerebroventriclePharmacol. Biochem. Behav.80289296Google Scholar
  122. 122.
    Yamamoto, M., McCaffery, P., Drager, U. C. 1996Influence of the choroid plexus on cerebellar development: analysis of retinoic acid synthesisBrain Res. Dev. Brain Res.93182190Google Scholar
  123. 123.
    Harbut, R. E., Johanson, C. E. 1986Third ventricle choroid plexus function and its response to acute perturbations in plasma chemistryBrain Res.374137146Google Scholar
  124. 124.
    Murphy, V. A., Johanson, C. E. 1990Na(+)–H+ exchange in choroid plexus and CSF in acute metabolic acidosis or alkalosisAm. J. Physiol.258F1528F1537Google Scholar
  125. 125.
    M. G. Netsky and S. Shuangshoti. Neoplasms of choroid plexus and ependyma. University of Virginia Press, Charlottesville, VA, 1975, pp. 265–304.Google Scholar
  126. 126.
    Stopa, E. G., Berzin, T. M., Kim, S., Song, P., Kuo-LeBlanc, V., Rodriguez-Wolf, M., Baird, A., Johanson, C. E. 2001Human choroid plexus growth factors: what are the implications for CSF dynamics in Alzheimer’s disease?Exp. Neurol.1674047Google Scholar
  127. 127.
    Whitelaw, A., Christie, S., Pople, I. 1999Transforming growth factor-beta1: a possible signal molecule for posthemorrhagic hydrocephalus?Pediatr Res.46576580Google Scholar
  128. 128.
    Whitelaw, A., Cherian, S., Thoresen, M., Pople, I. 2004Posthaemorrhagic ventricular dilatation: new mechanisms and new treatmentActa Paediatr. Suppl.931114Google Scholar
  129. 129.
    Johanson, C. E., Szmydynger-Chodobska, J., Chodobski, A., Baird, A., McMillan, P., Stopa, E. G. 1999Altered formation and bulk absorption of cerebrospinal fluid in FGF2-induced hydrocephalusAm. J. Physiol.277R263R271Google Scholar
  130. 130.
    Ohe, Y., Ishikawa, K., Itoh, Z., Tatemoto, K. 1996Cultured leptomeningeal cells secrete cerebrospinal fluid proteinsJ. Neurochem.67964971Google Scholar
  131. 131.
    Lignelid, H., Collins, V. P., Jacobsson, B. 1997Cystatin C and transthyretin expression in normal and neoplastic tissues of the human brain and pituitaryActa Neuropathol. (Berl).93494500Google Scholar
  132. 132.
    Palm, D. E., Knuckey, N. W., Primiano, M. J., Spangenberger, A. G., Johanson, C. E. 1995Cystatin C, a protease inhibitor, in degenerating rat hippocampal neurons following transient forebrain ischemiaBrain Res.69118Google Scholar
  133. 133.
    Katz, S. E., Klisovic, D. D., O’Dorisio, M. S., Lynch, R., Lubow, M. 2002Expression of somatostatin receptors 1 and 2 in human choroid plexus and arachnoid granulations: implications for idiopathic intracranial hypertensionArch. Ophthalmol.12015401543Google Scholar
  134. 134.
    Gard, A. L., Gavin, E., Solodushko, V., Pennica, D. 2004Cardiotrophin-1 in choroid plexus and the cerebrospinal fluid circulatory systemNeuroscience1274352Google Scholar
  135. 135.
    Hayaishi, O. 1999Prostaglandin D2 and sleep—a molecular genetic approachJ. Sleep Res.86064Google Scholar
  136. 136.
    Beuckmann, C. T., Lazarus, M., Gerashchenko, D., Mizoguchi, A., Nomura, S., Mohri, I., Uesugi, A., Kaneko, T., Mizuno, N., Hayaishi, O., Urade, Y. 2000Cellular localization of lipocalin-type prostaglandin D synthase (beta-trace) in the central nervous system of the adult ratJ. Comp. Neurol.4286278Google Scholar
  137. 137.
    Blodorn, B., Mader, M., Urade, Y., Hayaishi, O., Felgenhauer, K., Bruck, W. 1996Choroid plexus: the major site of mRNA expression for the beta-trace protein (prostaglandin D synthase) in human brainNeurosci. Lett.209117120Google Scholar
  138. 138.
    Hayaishi, O. 2000Molecular mechanisms of sleep–wake regulation: a role of prostaglandin D2Philos. Trans. R. Soc. Lond. B Biol. Sci.355275280Google Scholar
  139. 139.
    Weigel, R., Senn, P., Weis, J., Krauss, J. K. 2004Severe complications after intrathecal methotrexate (MTX) for treatment of primary central nervous system lymphoma (PCNSL)Clin. Neurol. Neurosurg.1068287Google Scholar
  140. 140.
    Lacasce, A., Howard, O., Lib, S., Fisher, D., Weng, A., Neuberg, D., Shipp, M. 2004Modified magrath regimens for adults with Burkitt and Burkitt-like lymphomas: preserved efficacy with decreased toxicityLeuk. Lymphoma45761767Google Scholar
  141. 141.
    Rubenstein, J. L., Combs, D., Rosenberg, J., Levy, A., McDermott, M., Damon, L., Ignoffo, R., Aldape, K., Shen, A., Lee, D., Grillo-Lopez, A., Shuman, M. A. 2003Rituximab therapy for CNS lymphomas: targeting the leptomeningeal compartmentBlood101466468Google Scholar
  142. 142.
    Pels, H., Schulz, H., Manzke, O., Hom, E., Thall, A., Engert, A. 2002Intraventricular and intravenous treatment of a patient with refractory primary CNS lymphoma using rituximabJ. Neuro-oncol.59213216Google Scholar
  143. 143.
    Chamberlain, M. C., Kormanik, P., Howell, S. B., Kim, S. 1995Pharmacokinetics of intralumbar DTC-101 for the treatment of leptomeningeal metastasesArch. Neurol.52912917Google Scholar
  144. 144.
    Glantz, M. J., Hall, W. A., Cole, B. F., Chozick, B. S., Shannon, C. M., Wahlberg, L., Akerley, W., Marin, L., Choy, H. 1995Diagnosis, management, and survival of patients with leptomeningeal cancer based on cerebrospinal fluid-flow statusCancer7529192931Google Scholar
  145. 145.
    Carder, P. J., Hume, R., Fryer, A. A., Strange, R. C., Lauder, J., Bell, J. E. 1990Glutathione S-transferase in human brainNeuropathol. Appl. Neurobiol.16293303Google Scholar
  146. 146.
    Weller, R. O. 1998Pathology of cerebrospinal fluid and interstitial fluid of the CNS: significance for Alzheimer disease, prion disorders and multiple sclerosisJ. Neuropathol. Exp. Neurol.57885894Google Scholar
  147. 147.
    Armstead, W. M. 2000NOC/oFQ contributes to hypoxic–ischemic impairment of N-methyl-d-aspartate-induced cerebral vasodilationBrain Res.8684855Google Scholar
  148. 148.
    Xu, H. L., Koenig, H. M., Ye, S., Feinstein, D. L., Pelligrino, D. A. 2004Influence of the glia limitans on pial arteriolar relaxation in the ratAm. J. Physiol.287H331H339Google Scholar
  149. 149.
    Jequier, S., Jequier, J. C. 1999Sonographic nomogram of the leptomeninges (pia–glial plate) and its usefulness for evaluating bacterial meningitis in infantsAm. J. Neuroradiol.2013591364Google Scholar
  150. 150.
    Toda, T. 2000Fukuyama-type congenital muscular dystrophyRinsho Shinkeigaku4012971299Google Scholar
  151. 151.
    Rash, J. E., Duffy, H. S., Dudek, F. E., Bilhartz, B. L., Whalen, L. R., Yasumura, T. 1997Grid-mapped freeze-fracture analysis of gap junctions in gray and white matter of adult rat central nervous system, with evidence for a “panglial syncytium” that is not coupled to neuronsJ. Comp. Neurol.388265292Google Scholar
  152. 152.
    Rash, J. E., Yasumura, T., Hudson, C. S., Agre, P., Nielsen, S. 1998Direct immunogold labeling of aquaporin-4 in square arrays of astrocyte and ependymocyte plasma membranes in rat brain and spinal cordProc. Natl. Acad. Sci. USA951198111986Google Scholar
  153. 153.
    Vajda, Z., Pedersen, M., Fuchtbauer, E. M., Wertz, K., Stodkilde-Jorgensen, H., Sulyok, E., Doczi, T., Neely, J. D., Agre, P., Frokiaer, J., Nielsen, S. 2002Delayed onset of brain edema and mislocalization of aquaporin-4 in dystrophin-null transgenic miceProc. Natl. Acad. Sci. USA991313113136Google Scholar
  154. 154.
    Hawrylak, N., Fleming, J. C., Salm, A. K. 1998Dehydration and rehydration selectively and reversibly alter glial fibrillary acidic protein immunoreactivity in the rat supraoptic nucleus and subjacent glial limitansGlia22260271Google Scholar
  155. 155.
    Yamamoto, T., Kato, Y., Karita, M., Takeiri, H., Muramatsu, F., Kobayashi, M., Saito, K., Osawa, M. 2002Fukutin expression in glial cells and neurons: implication in the brain lesions of Fukuyama congenital muscular dystrophyActa Neuropathol. (Berl)104217224Google Scholar
  156. 156.
    Moore, S. A., Saito, F., Chen, J., Michele, D. E., Henry, M. D., Messing, A., Cohn, R. D., Ross-Barta, S. E., Westra, S., Williamson, R. A., Hoshi, T., Campbell, K. P. 2002Deletion of brain dystroglycan recapitulates aspects of congenital muscular dystrophyNature418422425Google Scholar
  157. 157.
    Scripter, J. L., Ko, J., Kow, K., Arimura, A., Ide, C. F. 1997Regulation by interleukin-1beta of formation of a line of delimiting astrocytes following prenatal trauma to the brain of the mouseExp. Neurol.145329341Google Scholar
  158. 158.
    Shearer, M. C., Fawcett, J. W. 2001The astrocyte/meningeal cell interface—a barrier to successful nerve regeneration?Cell Tissue Res.305267273Google Scholar
  159. 159.
    Yamamoto, T., Kato, Y., Karita, M., Takeiri, H., Muramatsu, F., Kobayashi, M., Saito, K., Osawa, M. 2002Fukutin expression in glial cells and neurons: implication in the brain lesions of Fukuyama congenital muscular dystrophyActa Neuropathol. (Berl)104217224Google Scholar
  160. 160.
    Yonezawa, T., Ohtsuka, A., Yoshitaka, T., Hirano, S., Nomoto, H., Yamamoto, K., Ninomiya, Y. 2003Limitrin, a novel immunoglobulin superfamily protein localized to glia limitans formed by astrocyte endfeetGlia44190204Google Scholar
  161. 161.
    Komatsu, S., Sakata-Haga, H., Sawada, K., Hisano, S., Fukui, Y. 2001Prenatal exposure to ethanol induces leptomeningeal heterotopia in the cerebral cortex of the rat fetusActa Neuropathol. (Berl)1012226Google Scholar
  162. 162.
    Kakita, A., Wakabayashi, K., Su, M., Piao, Y. S., Takahashi, H. 2001Experimentally induced leptomeningeal glioneuronal heterotopia and underlying cortical dysplasia of the lateral limbic area in rats treated transplacentally with methylmercuryJ. Neuropathol. Exp. Neurol.60768777Google Scholar
  163. 163.
    Andjelkovic, A. V., Zochowski, M. R., Morgan, F., Pachter, J. S. 2001Qualitative and quantitative analysis of monocyte transendothelial migration by confocal microscopy and three-dimensional image reconstructionIn Vitro Cell Dev. Biol. Anim.37111120Google Scholar
  164. 164.
    Konsman, J. P., Tridon, V., Dantzer, R. 2000Diffusion and action of intracerebroventricularly injected interleukin-1 in the CNSNeuroscience101957967Google Scholar
  165. 165.
    Abbott, N. J. 2004Evidence for bulk flow of brain interstitial fluid: significance for physiology and pathologyNeurochem. Int.45545552Google Scholar
  166. 166.
    Nicoll, J. A., Yamada, M., Frackowiak, J., Mazur-Kolecka, B., Weller, R. O. 2004Cerebral amyloid angiopathy plays a direct role in the pathogenesis of Alzheimer’s disease. Pro-CAA position statementNeurobiol. Aging25589597Google Scholar
  167. 167.
    Bjelke, B., England, R., Nicholson, C., Rice, M. E., Lindberg, J., Zoli, M., Agnati, L. F., Fuxe, K. 1995Long distance pathways of diffusion for dextran along fibre bundles in brain. Relevance for volume transmissionNeuroReport610051009Google Scholar
  168. 168.
    Kivisakk, P., Mahad, D. J., Callahan, M. K., Trebst, C., Tucky, B., Wei, T., Wu, L., Baekkevold, E. S., Lassmann, H., Staugaitis, S. M., Campbell, J. J., Ransohoff, R. M. 2003Human cerebrospinal fluid central memory CD4+ T cells: evidence for trafficking through choroid plexus and meninges via P-selectinProc. Natl. Acad. Sci. USA10083898394Google Scholar
  169. 169.
    Zhang, E. T., Richards, H. K., Kida, S., Weller, R. O. 1992Directional and compartmentalised drainage of interstitial fluid and cerebrospinal fluid from the rat brainActa Neuropathol. (Berl)83233239Google Scholar
  170. 170.
    Cserr, H. F., Cooper, D. N., Suri, P. K., Patlak, C. S. 1981Efflux of radiolabeled polyethylene glycols and albumin from rat brainAm. J. Physiol.240F319F328Google Scholar
  171. 171.
    Bobo, R. H., Laske, D. W., Akbasak, A., Morrison, P. F., Dedrick, R. L., Oldfield, E. H. 1994Convection-enhanced delivery of macromolecules in the brainProc. Natl. Acad. Sci. USA9120762080Google Scholar
  172. 172.
    Nilsson, C., Lindvall-Axelsson, M., Owman, C. 1992Neuroendocrine regulatory mechanisms in the choroid plexus–cerebrospinal fluid systemBrain Res. Brain Res. Rev.17109138Google Scholar
  173. 173.
    Walker, M. C., Tong, X., Perry, H., Alavijeh, M. S., Patsalos, P. N. 2000Comparison of serum, cerebrospinal fluid and brain extracellular fluid pharmacokinetics of lamotrigineBr. J. Pharmacol.130242248Google Scholar
  174. 174.
    Logan, A., Frautschy, S. A., Gonzalez, A. M., Sporn, M. B., Baird, A. 1992Enhanced expression of transforming growth factor beta 1 in the rat brain after a localized cerebral injuryBrain Res.587216225Google Scholar
  175. 175.
    Logan, A., Gonzalez, A. M., Hill, D. J., Berry, M., Gregson, N. A., Baird, A. 1994Coordinated pattern of expression and localization of insulin-like growth factor-II (IGF-II) and IGF-binding protein-2 in the adult rat brainEndocrinology13522552264Google Scholar
  176. 176.
    Ohta, M., Suzuki, Y., Noda, T., Ejiri, Y., Dezawa, M., Kataoka, K., Chou, H., Ishikawa, N., Matsumoto, N., Iwashita, Y., Mizuta, E., Kuno, S., Ide, C. 2004Bone marrow stromal cells infused into the cerebrospinal fluid promote functional recovery of the injured rat spinal cord with reduced cavity formationExp. Neurol.187266278Google Scholar
  177. 177.
    Mazzini, L., Fagioli, F., Boccaletti, R., Mareschi, K., Oliveri, G., Olivieri, C., Pastore, I., Marasso, R., Madon, E. 2003Stem cell therapy in amyotrophic lateral sclerosis: a methodological approach in humansAmyotroph. Lateral Scler. Other Mot. Neuron Disord.4158161Google Scholar
  178. 178.
    Goldsmith, H. S., Wu, W., Zhong, J., Edgar, M. 2003Omental transposition to the brain as a surgical method for treating Alzheimer’s diseaseNeurol. Res.25625634Google Scholar
  179. 179.
    Goldsmith, H. S. 2002Treatment of Alzheimer’s disease by transposition of the omentumAnn. N. Y. Acad. Sci.977454467Google Scholar
  180. 180.
    Dujovny, M., Ding, Y. H., Ding, Y., Agner, C., Perez-Arjona, E. 2004Current concepts on the expression of neurotrophins in the greater omentumNeurol. Res.26226229Google Scholar
  181. 181.
    Chakrabortty, S., Kitada, M., Matsumoto, N., Taketomi, M., Kimura, K., Ide, C. 2000Choroid plexus ependymal cells enhance neurite outgrowth from dorsal root ganglion neurons in vitroJ. Neurocytol.29707717Google Scholar
  182. 182.
    Ide, C., Kitada, M., Chakrabortty, S., Taketomi, M., Matsumoto, N., Kikukawa, S., Mizoguchi, A., Kawaguchi, S., Endoh, K., Suzuki, Y. 2001Grafting of choroid plexus ependymal cells promotes the growth of regenerating axons in the dorsal funiculus of rat spinal cord: a preliminary reportExp. Neurol.167242251Google Scholar
  183. 183.
    Borlongan, C. V., Skinner, S. J., Geaney, M., Vasconcellos, A. V., Elliott, R. B., Emerich, D. F. 2004CNS grafts of rat choroid plexus protect against cerebral ischemia in adult ratsNeuroReport1515431547Google Scholar
  184. 184.
    Borlongan, C. V., Skinner, S. J., Geaney, M., Vasconcellos, A. V., Elliott, R. B., Emerich, D. F. 2004Intracerebral transplantation of porcine choroid plexus provides structural and functional neuroprotection in a rodent model of strokeStroke3522062210Google Scholar
  185. 185.
    Emerich, D. F., Vasconcellos, A. V., Elliott, R. B., Skinner, S. J., Borlongan, C. V. 2004The choroid plexus: function, pathology and therapeutic potential of its transplantationExp. Opin. Biol. Ther.411911201Google Scholar
  186. 186.
    Driesse, M. J., Kros, J. M., Avezaat, C. J., Valerio, D., Vecht, C. J., Bout, A., Smitt, P. A. 1999Distribution of recombinant adenovirus in the cerebrospinal fluid of nonhuman primatesHum. Gene Ther.1023472354Google Scholar
  187. 187.
    Haskell, R. E., Hughes, S. M., Chiorini, J. A., Alisky, J. M., Davidson, B. L. 2003Viral-mediated delivery of the late-infantile neuronal ceroid lipofuscinosisgene, TPP-I to the mouse central nervous systemGene Ther.103442Google Scholar
  188. 188.
    Shi, N., Pardridge, W. M. 2000Noninvasive gene targeting to the brainProc. Natl. Acad. Sci. USA9775677572Google Scholar
  189. 189.
    Oshiro, E. M., Viola, J. J., Oldfield, E. H., Walbridge, S., Bacher, J., Frank, J. A., Blaese, R. M., Ram, Z. 1995Toxicity studies and distribution dynamics of retroviral vectors following intrathecal administration of retroviral vector-producer cellsCancer Gene Ther.28795Google Scholar
  190. 190.
    Wang, C., Wang, C. M., Clark, K. R., Sferra, T. J. 2003Recombinant AAV serotype 1 transduction efficiency and tropism in the murine brainGene Ther.1015281534Google Scholar
  191. 191.
    Lehtolainen, P., Tyynela, K., Kannasto, J., Airenne, K. J., Yla-Herttuala, S. 2002Baculoviruses exhibit restricted cell type specificity in rat brain: a comparison of baculovirus- and adenovirus-mediated intracerebral gene transfer in vivoGene Ther.916931699Google Scholar
  192. 192.
    Zheng, Y., Rozengurt, N., Ryazantsev, S., Kohn, D. B., Satake, N., Neufeld, E. F. 2003Treatment of the mouse model of mucopolysaccharidosis I with retrovirally transduced bone marrowMol. Genet. Metab.79233244Google Scholar
  193. 193.
    Alexander, I. E., Russell, D. W., Spence, A. M., Miller, A. D. 1996Effects of gamma irradiation on the transduction of dividing and nondividing cells in brain and muscle of rats by adeno-associated virus vectorsHum. Gene Ther.7841850Google Scholar
  194. 194.
    Lai, Z., Han, I., Zirzow, G., Brady, R. O., Reiser, J. 2000Intercellular delivery of a herpes simplex virus VP22 fusion protein from cells infected with lentiviral vectorsProc. Natl. Acad. Sci. USA971129711302Google Scholar
  195. 195.
    Kumai, Y., Ooboshi, H., Kitazono, T., Takada, J., Ibayashi, S., Fujishima, M., Iida, M. 2003Brain ischemia augments exo-focal transgene expression of adenovirus-mediated gene transfer to ependyma in hypertensive ratsExp. Neurol.184904911Google Scholar
  196. 196.
    Toyoda, K., Nakane, H., Heistad, D. D. 2001Cationic polymer and lipids augment adenovirus-mediated gene transfer to cerebral arteries in vivoJ. Cereb. Blood Flow Metab.2111251131Google Scholar
  197. 197.
    Ghodsi, A., Stein, C., Derksen, T., Martins, I., Anderson, R. D., Davidson, B. L. 1999Systemic hyperosmolality improves beta-glucuronidase distribution and pathology in murine MPS VII brain following intraventricular gene transferExp. Neurol.160109116Google Scholar
  198. 198.
    Rosenfeld, M. R., Bergman, I., Schramm, L., Griffin, J. A., Kaplitt, M. G., Meneses, P. I. 1997Adeno-associated viral vector gene transfer into leptomeningeal xenograftsJ. Neuro-oncol.34139144Google Scholar
  199. 199.
    Ono, S., Komuro, T., Macdonald, R. L. 2002Heme oxygenase-1 gene therapy for prevention of vasospasm in ratsJ. Neurosurg.9610941102Google Scholar
  200. 200.
    Benraiss, A., Chmielnicki, E., Lerner, K., Roh, D., Goldman, S. A. 2001Adenoviral brain-derived neurotrophic factor induces both neostriatal and olfactory neuronal recruitment from endogenous progenitor cells in the adult forebrainJ. Neurosci.2167186731Google Scholar
  201. 201.
    Matsuoka, N., Nozaki, K., Takagi, Y., Nishimura, M., Hayashi, J., Miyatake, S., Hashimoto, N. 2003Adenovirus-mediated gene transfer of fibroblast growth factor-2 increases BrdU-positive cells after forebrain ischemia in gerbilsStroke3415191525Google Scholar
  202. 202.
    Yoshimura, S., Morishita, R., Hayashi, K., Kokuzawa, J., Aoki, M., Matsumoto, K., Nakamura, T., Ogihara, T., Sakai, N., Kaneda, Y. 2002Gene transfer of hepatocyte growth factor to subarachnoid space in cerebral hypoperfusion modelHypertension3910281034Google Scholar
  203. 203.
    Shimamura, M., Sato, N., Oshima, K., Aoki, M., Kurinami, H., Waguri, S., Uchiyama, Y., Ogihara, T., Kaneda, Y., Morishita, R. 2004Novel therapeutic strategy to treat brain ischemia: overexpression of hepatocyte growth factor gene reduced ischemic injury without cerebral edema in rat modelCirculation109424431Google Scholar
  204. 204.
    Hayashi, K., Morishita, R., Nakagami, H., Yoshimura, S., Hara, A., Matsumoto, K., Nakamura, T., Ogihara, T., Kaneda, Y., Sakai, N. 2001Gene therapy for preventing neuronal death using hepatocyte growth factor: in vivo gene transfer of HGF to subarachnoid space prevents delayed neuronal death in gerbil hippocampal CA1 neuronsGene Ther.811671173Google Scholar
  205. 205.
    Oshima, K., Shimamura, M., Mizuno, S., Tamai, K., Doi, K., Morishita, R., Nakamura, T., Kubo, T., Kaneda, Y. 2004Intrathecal injection of HVJ-E containing HGF gene to cerebrospinal fluid can prevent and ameliorate hearing impairment in ratsFASEB J.18212214Google Scholar
  206. 206.
    Larocca, D., Burg, M. A., Jensen-Pergakes, K., Ravey, E. P., Gonzalez, A. M., Baird, A. 2002Evolving phage vectors for cell targeted gene deliveryCurr. Pharm. Biotechnol.34557Google Scholar
  207. 207.
    Larocca, D., Witte, A., Johnson, W., Pierce, G. F., Baird, A. 1998Targeting bacteriophage to mammalian cell surface receptors for gene deliveryHum. Gene Ther.923932399Google Scholar
  208. 208.
    Szmydynger-Chodobska, J., Chun, Z. G., Johanson, C. E., Chodobski, A. 2002Distribution of fibroblast growth factor receptors and their co-localization with vasopressin in the choroid plexus epitheliumNeuroReport13257259Google Scholar
  209. 209.
    Petito, C. K. 2004Human immunodeficiency virus type 1 compartmentalization in the central nervous systemJ. Neurovirol.102124Google Scholar
  210. 210.
    Chen, H., Wood, C., Petito, C. K. 2000Comparisons of HIV-1 viral sequences in brain, choroid plexus and spleen: potential role of choroid plexus in the pathogenesis of HIV encephalitisJ. Neurovirol.6498506Google Scholar
  211. 211.
    Levine, S. 1987Choroid plexus: target for systemic disease and pathway to the brainLab. Invest.56231233Google Scholar
  212. 212.
    Bragg, D. C., Hudson, L. C., Liang, Y. H., Tompkins, M. B., Fernandes, A., Meeker, R. B. 2002Choroid plexus macrophages proliferate and release toxic factors in response to feline immunodeficiency virusJ. Neurovirol.8225239Google Scholar
  213. 213.
    Bragg, D. C., Childers, T. A., Tompkins, M. B., Tompkins, W. A., Meeker, R. B. 2002Infection of the choroid plexus by feline immunodeficiency virusJ. Neurovirol.8211224Google Scholar
  214. 214.
    Chodobski, A., Chung, I., Kozniewska, E., Ivanenko, T., Chang, W., Harrington, J. F., Duncan, J. A., Szmydynger-Chodobska, J. 2003Early neutrophilic expression of vascular endothelial growth factor after traumatic brain injuryNeuroscience122853867Google Scholar
  215. 215.
    Oldstone, M. B., Southern, P. J. 1993Trafficking of activated cytotoxic T lymphocytes into the central nervous system: use of a transgenic modelJ. Neuroimmunol.462531Google Scholar
  216. 216.
    Thibeault, I., Laflamme, N., Rivest, S. 2001Regulation of the gene encoding the monocyte chemoattractant protein 1 (MCP-1) in the mouse and rat brain in response to circulating LPS and proinflammatory cytokinesJ. Comp. Neurol.434461477Google Scholar
  217. 217.
    Liu, Y., Tang, X. P., McArthur, J. C., Scott, J., Gartner, S. 2000Analysis of human immunodeficiency virus type 1gp160 sequences from a patient with HIV dementia: evidence for monocyte trafficking into brainJ. Neurovirol.6S70S81Google Scholar
  218. 218.
    Brew, B. J., Pemberton, L., Ray, J. 2004Can the peripheral blood monocyte count be used as a marker of CSF resistance to antiretroviral drugs?J. Neurovirol.103843Google Scholar
  219. 219.
    Cwirla, S. E., Peters, E. A., Barrett, R. W., Dower, W. J. 1990Peptides on phage: a vast library of peptides for identifying ligandsProc. Natl. Acad. Sci. USA8763786382Google Scholar
  220. 220.
    Cortese, R., Monaci, P., Luzzago, A., Santini, C., Bartoli, F., Cortese, I., Fortugno, P., Galfre, G., Nicosia, A., Felici, F. 1996Selection of biologically active peptides by phage display of random peptide librariesCurr. Opin. Biotechnol.7616621Google Scholar
  221. 221.
    Sidhu, S. S., Lowman, H. B., Cunningham, B. C., Wells, J. A. 2000Phage display for selection of novel binding peptidesMethods Enzymol.328333363Google Scholar
  222. 222.
    Buchli, P. J., Wu, Z., Ciardelli, T. L. 1997The functional display of interleukin-2 on filamentous phageArch. Biochem. Biophys.3397984Google Scholar
  223. 223.
    Larocca, D., Jensen-Pergakes, K., Burg, M. A., Baird, A. 2001Receptor-targeted gene delivery using multivalent phagemid particlesMol. Ther.3476484Google Scholar
  224. 224.
    Kassner, P. D., Burg, M. A., Baird, A., Larocca, D. 1999Genetic selection of phage engineered for receptor-mediated gene transfer to mammalian cellsBiochem. Biophys. Res. Commun.264921928Google Scholar
  225. 225.
    Quan, N., Herkenham, M. 2002Connecting cytokines and brain: a review of current issuesHistol. Histopathol.17273288Google Scholar
  226. 226.
    Rivest, S. 2003Molecular insights on the cerebral innate immune systemBrain Behav. Immun.171319Google Scholar
  227. 227.
    Quan, N., Sundar, S. K., Weiss, J. M. 1994Induction of interleukin-1 in various brain regions after peripheral and central injections of lipopolysaccharideJ. Neuroimmunol.49125134Google Scholar
  228. 228.
    Herkenham, M., Lee, H. Y., Baker, R. A. 1998Temporal and spatial patterns of c-fos mRNA induced by intravenous interleukin-1: a cascade of non-neuronal cellular activation at the blood–brain barrierJ. Comp. Neurol.400175196Google Scholar
  229. 229.
    Zekki, H., Feinstein, D. L., Rivest, S. 2000The clinical course of experimental autoimmune encephalomyelitis is associated with a profound and sustained transcriptional activation of the genes encoding Toll-like receptor 2 and CD14 in the mouse CNSBrain Pathol.12308319Google Scholar
  230. 230.
    Laflamme, N., Rivest, S. 2001Toll-like receptor 4: the missing link of the cerebral innate immune response triggered by circulating gram-negative bacterial cell wall componentsFASEB J.15155163Google Scholar
  231. 231.
    Meeker, R. B., Boles, J. C., Bragg, D. C., Robertson, K., Hall, C. 2004Development of neuronal sensitivity to toxins in cerebrospinal fluid from HIV-type 1-infected individualsAIDS Res. Hum. Retrovir.2010721086Google Scholar
  232. 232.
    Benjelloun, N., Charriaut-Marlangue, C., Hantaz-Ambroise, D., Menard, A., Pierig, R., Alliel, P. M., Rieger, F. 2002Induction of cell death in rat brain by a gliotoxic factor from cerebrospinal fluid in multiple sclerosisCell. Mol. Biol.48205212Google Scholar
  233. 233.
    Liu, Y., Tang, X. P., McArthur, J. C., Scott, J., Gartner, S. 2000Analysis of human immunodeficiency virus type 1 gp160 sequences from a patient with HIV dementia: evidence for monocyte trafficking into brainJ. Neurovirol.6S70S81Google Scholar
  234. 234.
    Banks, W. A., Freed, E. O., Wolf, K. M., Robinson, S. M., Franko, M., Kumar, V. B. 2001Transport of human immunodeficiency virus type 1 pseudoviruses across the blood–brain barrier: role of envelope proteins and adsorptive endocytosisJ. Virol.7546814691Google Scholar
  235. 235.
    Gibbs, J. E., Thomas, S. A. 2002The distribution of the anti-HIV drug, 2′3′-dideoxycytidine (ddC), across the blood–brain and blood–cerebrospinal fluid barriers and the influence of organic anion transport inhibitorsJ. Neurochem.80392404Google Scholar
  236. 236.
    Gibbs, J. E., Jayabalan, P., Thomas, S. A. 2003Mechanisms by which 2′,3′-dideoxyinosine (ddI) crosses the guinea-pig CNS barriers; relevance to HIV therapyJ. Neurochem.84725734Google Scholar
  237. 237.
    Gibbs, J. E., Rashid, T., Thomas, S. A. 2003Effect of transport inhibitors and additional anti-HIV drugs on the movement of lamivudine (3TC) across the guinea pig brain barriersJ. Pharmacol. Exp. Ther.30610351041Google Scholar
  238. 238.
    Strazielle, N., Belin, M. F., Ghersi-Egea, J. F. 2003Choroid plexus controls brain availability of anti-HIV nucleoside analogs via pharmacologically inhibitable organic anion transportersAIDS1714731485Google Scholar
  239. 239.
    Dogruel, M., Gibbs, J. E., Thomas, S. A. 2003Hydroxyurea transport across the blood–brain and blood–cerebrospinal fluid barriers of the guinea-pigJ. Neurochem.877684Google Scholar
  240. 240.
    Anthonypillai, C., Sanderson, R. N., Gibbs, J. E., Thomas, S. A. 2004The distribution of the HIV protease inhibitor, ritonavir, to the brain, cerebrospinal fluid, and choroid plexuses of the guinea pigJ. Pharmacol. Exp. Ther.308912920Google Scholar
  241. 241.
    Engelhardt, B., Wolburg-Buchholz, K., Wolburg, H. 2001Involvement of the choroid plexus in central nervous system inflammationMicrosc. Res. Tech.52112129Google Scholar
  242. 242.
    Martino, G., Furlan, R., Comi, G., Adorini, L. 2001The ependymal route to the CNS: an emerging gene-therapy approach for MSTrends Immunol.22483490Google Scholar
  243. 243.
    Reynolds, B. A., Weiss, S. 1992Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous systemScience25517071710Google Scholar
  244. 244.
    Martens, D. J., Seaberg, R. M., Kooy, D. 2002In vivo infusions of exogenous growth factors into the fourth ventricle of the adult mouse brain increase the proliferation of neural progenitors around the fourth ventricle and the central canal of the spinal cordEur. J. Neurosci.1610451057Google Scholar
  245. 245.
    Craig, C. G., Tropepe, V., Morshead, C. M., Reynolds, B. A., Weiss, S., Kooy, D. 1996In vivo growth factor expansion of endogenous subependymal neural precursor cell populations in the adult mouse brainJ. Neurosci.1626492658Google Scholar
  246. 246.
    Aleksandrova, M. A., Poltavtseva, R. A., Revishchin, A. V., Korochkin, L. I., Sukhikh, G. T. 2004Development of neural stem/progenitor cells from human brain by transplantation into the brains of adult ratsNeurosci. Behav. Physiol.34659662Google Scholar
  247. 247.
    Uchida, K., Mukai, M., Okano, H., Kawase, T. 2004Possible oncogenicity of subventricular zone neural stem cells: case reportNeurosurgery55977978Google Scholar
  248. 248.
    Mattson, M. P., Maudsley, S., Martin, B. 2004BDNF and 5-HT: a dynamic duo in age-related neuronal plasticity and neurodegenerative disordersTrends Neurosci.27589594Google Scholar
  249. 249.
    Deguchi, Y., Naito, T., Yuge, T., Furukawa, A., Yamada, S., Pardridge, W. M., Kimura, R. 2000Blood–brain barrier transport of 125I-labeled basic fibroblast growth factorPharm. Res.176369Google Scholar
  250. 250.
    Johanson, C., McMillan, P., Tavares, R., Spangenberger, A., Silverberg, G., Stopa, E. 2004Homeostatic capabilities of the choroid plexus epithelium in Alzheimer’s diseaseCerebrospinal Fluid Res.1116Google Scholar
  251. 251.
    Dworkin, L. D., Gong, R., Tolbert, E., Centracchio, J., Yano, N., Zanabli, A. R., Esparza, A., Rifai, A. 2004Hepatocyte growth factor ameliorates progression of interstitial fibrosis in rats with established renal injuryKidney Int.65409419Google Scholar
  252. 252.
    Wyss-Coray, T., Feng, L., Masliah, E., Ruppe, M. D., Lee, H. S., Toggas, S. M., Rockenstein, E. M., Mucke, L. 1995Increased central nervous system production of extracellular matrix components and development of hydrocephalus in transgenic mice overexpressing transforming growth factor-beta 1Am. J. Pathol.1475367Google Scholar
  253. 253.
    Johanson, C. E., Gonzalez, A. M., Stopa, E. G. 2001Water-imbalance-induced expression of FGF-2 in fluid-regulatory centers: choroid plexus and neurohypophysisEur. J. Pediatr. Surg.11S37S38Google Scholar
  254. 254.
    Hakvoort, A., Johanson, C. E. 2000Growth factor modulation of CSF formation by isolated choroid plexus: FGF-2 vs. TGF-beta1Eur. J. Pediatr. Surg.104446Google Scholar
  255. 255.
    Silverberg, G. D., Mayo, M., Saul, T., Rubenstein, E., McGuire, D. 2003Alzheimer’s disease, normal-pressure hydrocephalus, and senescent changes in CSF circulatory physiology: a hypothesisLancet Neurol.2506511Google Scholar
  256. 256.
    Silverberg, G. D., Heit, G., Huhn, S., Jaffe, R. A., Chang, S. D., Bronte-Stewart, H., Rubenstein, E., Possin, K., Saul, T. 2001The cerebrospinal fluid production rate is reduced in dementia of the Alzheimer’s typeNeurology5717631766Google Scholar
  257. 257.
    Deane, R., Wu, Z., Sagare, A., Davis, J., Du Yan, S., Hamm, K., Xu, F., Parisi, M., LaRue, B., Hu, H. W., Spijkers, P., Guo, H., Song, X., Lenting, P. J., Nostrand, W. E., Zlokovic, B. V. 2004LRP/amyloid beta-peptide interaction mediates differential brain efflux of Abeta isoformsNeuron43333344Google Scholar
  258. 258.
    Spector, R. 1981Penetration of ascorbic acid from cerebrospinal fluid into brainExp. Neurol.72645653Google Scholar
  259. 259.
    Miller, D. S. 2004Confocal imaging of xenobiotic transport across the choroid plexusAdv. Drug Deliv. Rev.5618111824Google Scholar
  260. 260.
    Gao, B., Hagenbuch, B., Kullak-Ublick, G. A., Benke, D., Aguzzi, A., Meier, P. J. 2000Organic anion-transporting polypeptides mediate transport of opioid peptides across blood–brain barrierJ. Pharmacol. Exp. Ther.2947379Google Scholar
  261. 261.
    Strikic, N., Klarica, M., Vladic, A., Bulat, M. 1994Effect of active transport on distribution and concentration gradients of (3H)benzylpenicillin in the cerebrospinal fluidNeurosci. Lett.169159162Google Scholar
  262. 262.
    Habgood, M. D., Begley, D. J., Abbott, N. J. 2000Determinants of passive drug entry into the central nervous systemCell. Mol. Neurobiol.20231253Google Scholar
  263. 263.
    Banks, W. A. 2004Are the extracellular pathways a conduit for the delivery of therapeutics to the brain?Curr. Pharm. Des.1013651370Google Scholar
  264. 264.
    Saunders, N. R., Habgood, M. D., Dziegielewska, K. M. 1999Barrier mechanisms in the brain: I. Adult brainClin. Exp. Pharmacol. Physiol.261119Google Scholar
  265. 265.
    Shen, D. D., Artru, A. A., Adkison, K. K. 2004Principles and applicability of CSF sampling for the assessment of CNS drug delivery and pharmacodynamicsAdv. Drug Deliv. Rev.5618251857Google Scholar
  266. 266.
    Zheng, W., Deane, R., Redzic, Z., Preston, J. E., Segal, M.B. 2003Transport of l-[125I]thyroxine by in situ perfused ovine choroid plexus: inhibition by lead exposureJ. Toxicol. Environ. Health A66435451Google Scholar
  267. 267.
    Spector, R. 2000Drug transport in the mammalian central nervous system: multiple complex systems. A critical analysis and commentaryPharmacology605873Google Scholar

Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Conrad E. Johanson
    • 1
    • 5
  • John A. Duncan
    • 1
  • Edward G. Stopa
    • 2
  • Andrew Baird
    • 3
    • 4
  1. 1.Department of Clinical NeurosciencesRhode Island Hospital, Brown Medical SchoolProvidenceUSA
  2. 2.Department of PathologyRhode Island Hospital, Brown Medical SchoolProvidenceUSA
  3. 3.Human BioMolecular Research InstituteSan DiegoUSA
  4. 4.Molecular Neuroscience Group, School of MedicineUniversity of BirminghamEdgbastonUK
  5. 5.Department of NeurosurgeryRhode Island HospitalProvidenceUSA

Personalised recommendations