Abstract
The uptake and incorporation by brain of blood-borne free fatty acids (FFA) is a topic with important physiological and diagnostic ramifications. The passage of FFA from blood into brain requires penetration through the blood-brain barrier (BBB). We review here the basic principles that underlie the concept of the BBB as they apply to FFA permeability and how such principles can be used to study brain FFA metabolism in health and disease.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Alberghina, M., Lupo, G., Anfuso, C. D., and Infarinato, S. (1994) Differential transport of docosahexaenoate and palmitate through the blood-retina and blood-brain barrier of the rat. Neurosci. Lett. 171, 133–136.
Anderson, G. J. and Connor, W. E. (1988) Uptake of fatty acids by the developing rat brain. Lipids 23, 286–290.
Arai, T., Wakabayashi, S., Channing, M. A., Dunn, B. B., Der, M. G., Bell, J. M., Herscovitch, P., Eckelman, W. C., Rapoport, S. I., and Chang, M. C. (1995) Incorporation of [1-carbon-11]palmitate in monkey brain using positron emission tomography. J. Nuclear Med. 36, 2261–2267.
Banks, W. A. and Kastin, A. J. (1990) Editorial review: peptide transport systems for opiates across the blood-brain barrier. Am. J. Physiol. 259, El-E10.
Banks, W. A. and Kastin, A. J. (1993) Peptide binding in blood and passage across the blood-brain barrier, in Proceedings of the International Symposium on Blood Binding and Drug Transfer ( Tillement, J. P., Eckert, H., Albengres, E., Barre, J., Baumann, P., Belpare, F., and Lemaire, M., eds.), Fort and Clair, Paris, pp. 223–242.
Begley, D. J. (1992) The interaction of some centrally active drugs with the blood- brain barrier and circumventricular organs. Prog. Brain Res. 91, 163–169.
Betz, A. L. and Goldstein, G. W. (1978) Polarity of the blood-brain barrier: neutral amino acid transport into isolated brain capillaries. Science (Washington, DC) 202, 225–227.
Bradbury, M. W. B., Segal, M. B., and Wilson, J. (1972) Transport of potassium at the blood-brain barrier. J. Physiol. (Lond.) 221, 617–632.
Chang, M. C. J., Arai, T., Freed, L. M., Wakabayashi, S., Channing, M. A., Dunn, B. B., Der, M. G., Bell, J. M., Herscovitch, P., Eckelman, W. C., and Rapoport, S. I. (1996) Brain incorporation of [1-11C] arachidonate in normocapnic and hypercapnic monkeys: a PET study. J. Cereb. Blood Flow Metab. (in press).
Chikhale, E. G., Ng, K. Y., Burton, P. S., and Borchardt, R. T. (1994) Hydrogen bonding potential as a determinant of the in vitro and in situ blood-brain barrier permeability of peptides. Pharm. Res. 11, 412–419.
Cordon-Cardo, C., O’Brien, J. P., Casals, D., Rittman-Grauer, L., Biedler, J. L., Melamed, M. R., and Bertino, J. R. (1989) Multidrug-resistance gene (P-glycoprotein) is expressed by endothelial cells at blood-brain barrier sites. Proc. Nat. Acad. Sci. USA 86, 695–698.
Dayson, H., Welch, K., and Segal, M. B. (1987a) Blood-brain-CSF relations, in The Physiology and Pathophysiology of the Cerebrospinal Fluid, Churchill Livingstone, Edinburgh, pp. 375–451.
Dayson, H., Welch, K., and Segal, M. B. (1987b) Morphological aspects of the barriers, in The Physiology and Pathophysiology of the Cerebrospinal Fluid, Churchill Livingstone, Edinburgh, pp. 105–188.
DeGeorge, J. J., Nariai, T., Yamazaki, S., Williams, W. M., and Rapoport, S. I. (1991) Arecoline-stimulated brain incorporation of intravenously administered fatty acids in unanesthetized rats. J. Neurochem. 56, 352–355.
DeGeorge, J. J., Noronha, J. G., Bell, J., Robinson, P., and Rapoport, S. I. (1989) Intravenous injection of [1–14C] arachidonate to examine regional brain lipid metabolism in unanesthetized rats. J. Neurosci. Res. 24, 413 423.
Dhopeshwarkar, G. A. (1973) Uptake and transport of fatty acids into the brain and the role of the blood-brain barrier system. Adv. Lipid Res. 11, 109–142.
Drewes, L. R., Conway, W. P., and Gilboe, D. D. (1977) Net amino acid transport between plasma and erythrocytes and perfused dog brain. Am. J. Physiol. 2, E320 - E325.
Hussain, S. T. and Roots, B. I. (1994) Effect of essential fatty acid deficiency and immunopathological stresses on blood brain barrier (B-BB) in Lewis rats: a biochemical study. Biochem. Soc. Trans. 22, 338S.
Jacques, L. and Couture, R. (1990) Studies on the vascular permeability induced by intrathecal substance p and bradykinin in the rat. Eur. J. Pharm. 184, 9–20.
Johanson, C. E. (1988) The choroid plexus-arachnoid membrane-cerebrospinal fluid system, in Neuromethods: The Neuronal Microenvironment ( Boulton, A. A., Baker, G. B., and Walz, W., eds.), Humana Press, Clifton, NJ, pp. 33–104.
Jones, C. R., Arai, T., Bell, J. M., and Rapoport, S. I. (1995) Selective in vivo incorporation of [3H] arachidonic acid into rat brain synaptosomal fractions before and after cholinergic stimulation. Unpublished manuscript.
Kety, S. S. (1987) Cerebral circulation and its measurement by inert diffusible tracers, in Encyclopedia of Neuroscience vol. 1 ( Adelman, G., ed.), Birkhäuser, Boston, pp. 206–208.
Nariai, T., DeGeorge, J. J., Greig, N. H., and Rapoport, S. I. (1991) In vivo incorporation of [9,10–3H] palmitate into a rat metastatic brain-tumor mode. J. Neurosurg. 74, 643–649.
Nariai, T., DeGeorge, J. J., Lamour, Y., and Rapoport, S. I. (1991) In vivo brain incorporation of [1–14C] arachidonate in awake rats, with or without cholinergic stimulation, following unilateral lesioning of nucleus basalis magnocellularis. Brain Res. 559, 1–9.
Nariai, T., Greig, N. H., DeGeorge, J. J., Genka, S., and Rapoport, S. I. (1993) Intravenously injected radiolabelled fatty acids image brain tumour phospholipids in vivo: differential uptakes of palmitate, arachidonate and docosahexaenoate. Clin. Exp. Metastasis, 11, 141–149.
Nilsson, C., Lindvall-Axelsson, M., and Owman, C. (1992) Neuroendocrine regulatory mechanisms in the choroid plexus-cerebrospinal fluid system. Brain Res. Rev. 17, 109–138.
Noronha, J. G., Larson, D. M., and Rapoport, S. I. (1989) Regional cerebral incorporation of plasma [14C] palmitate, and cerebral glucose utilization, in water-deprived Long-Evans and Brattleboro rats. Exp. Neurol. 103, 267–276.
Oldendorf, W. H. (1973) Carrier-mediated blood-brain barrier transport of short-chain monocarboxylic organic acids. Am. J. Physiol., 224, 1450–1453.
Oldendorf, W. H. (1974) Lipid solubility and drug penetration of the blood-brain barrier. Proc. Soc. Exp. Biol. Med., 147, 813–816.
Pardridge, W. M. and Mietus, L. J. (1980) Palmitate and cholesterol transport through the blood-brain barrier. J. Neurochem. 34, 463–466.
Purdon, A. D., Arai, T., and Rapoport, S. I. (1995) No evidence for direct incorporation of esterified palmitic acid from plasma into brain lipids of awake adult rat. Unpublished manuscript.
Rapoport, S. I. (1976) Blood Brain Barrier in Physiology and Medicine. Raven, New York.
Rapoport, S. I. (1996) In vivo labeling of brain phospholipids by long-chain fatty acids: relation to turnover and function. Lipids (in press).
Rapoport, S. I. and Robinson, P. J. (1995) Long-chain fatty acid transport at the blood-brain barrier and incorporation into brain phospholipids: a new in vivo method for examining neuroplasticity, and brain second messenger systems involving phospholipase A2 activation, in New Concepts of a Blood-Brain Barrier ( Greenwood, J., ed.), Plenum, New York, pp. 119–140.
Robinson, R. J., Noronha, J. G., DeGeorge, J. J., Freed, L. M., Nariai, T., and Rapoport, S. I. (1992) A quantitative method for measuring regional in vivo fatty-acid incorporation into and turnover within brain phospholipids: review and critical analysis. Brain Res. Rev. 17, 187–214.
Scott, B. L. and Bazan, N. G. (1989) Membrane docosahexaenoate is supplied to the developing brain and retina by the liver. Proc. Natl. Acad. Sci. USA 86, 2903–2907.
Spector, R. (1988) Fatty acid transport through the blood-brain barrier. J. Neurochem. 50, 639–643.
Spector, R. and Lorenzo, A. V. (1974) The effects of salicylate and probenecid on the cerebrospinal fluid transport of penicillin, aminosalicylic acid and iodide. J. Pharm. Exp. Ther. 188, 55–65.
Tabata, H., Bell, J. M., Miller, J. C., and Rapoport, S. I. (1986) Incorporation of plasma palmitate into the brain of the rat during development. Devel. Brain Res. 29, 1–8.
Thiès, F., Delachambre, M. C., Bentejac, M., Lagarde, M., and Lecerf, J. (1992) Unsaturated fatty acids esterified in 2-acyl-1-lysophosphatidylcholine bound to albumin are more efficiently taken up by the young rat brain than the unesterified form. J. Neurochem. 59, 1110–1116.
Tone, O., Matsushima, Y., Inaba, Y., and Rapoport, S. I. (1990) Regional [14C] palmitate incorporation into the hippocampus after transient cerebral ischemia in awake gerbils. Adv. Neurol., 52, 141–148.
Tone, O., Miller, J. C., Bell, J. M., and Rapoport, S. I. (1988) Regional cerebral palmitate incorporation after unilateral auditory deprivation in immature and adult Fischer-344 rats. Exp. Neurol. 100, 491–505.
Tsuji, A., Terasaki, T., Takabatake, Y., Tenda, Y., Tamai, I., Yamashima, T., Moritani, S., Tsuruo, T., and Yamashita, J. (1992) P-glycoprotein as the drug efflux pump in primary cultured bovine brain capillary endothelial cells. Life Sci. 51, 1427–1437.
Wakabayashi, S., Freed, L. M., Bell, J. M., and Rapoport, S. I. (1994) In vivo cerebral incorporation of radiolabeled fatty acids after acute unilateral orbital enucleation in adult hooded Long-Evans rats. J. Cereb. Blood Flow Metab. 14, 312–323.
Wakabayashi, S., Freed, L. M., Chang, M., and Rapoport, S. I. (1995) In vivo imaging of brain incorporation of fatty acids and of 2-deoxy-D-glucose demonstrates functional and structural neuroplastic effects of chronic unilateral visual deprivation in rats. Brain Res. 679, 110–122.
Washizaki, K., Purdon, D., DeGeorge, J., Robinson, R. J., Rapoport, S. I., and Smith, Q. R. (1991) Fatty acid uptake and esterification by the in situ perfused rat brain. Soc. Neurosci. Abst. 17, 864.
Washizaki, K., Smith, Q. R., Rapoport, S. I., and Purdon, A. D. (1994) Brain arachidonic acid incorporation and precursor pool specific activity during intravenous infusion of unesterified [3H] arachidonate in the anesthetized rat. J. Neurochem. 63, 727–736.
Yamazaki, S., Noronha, J. G., Bell, J. M., and Rapoport, S. I. (1989) Incorporation of plasma [14C] palmitate into the hypoglossal nucleus following unilateral axotomy of the hypoglossal nerve in adult rat, with and without regeneration. Brain Res. 477, 19–28.
Ziylan, Z. Y., Bernard, G. C., Lefauconnier, J. M., Durand, G. A., and Bourre, J. M. (1992) Effect of dietary n-3 fatty acid deficiency on blood-to-brain transfer of sucrose, alpha-aminoisobutyric acid and phenylalanine in the rat. Neurosci. Lett. 137, 9–13.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1997 Springer Science+Business Media New York
About this chapter
Cite this chapter
Banks, W.A., Kastin, A.J., Rapoport, S.I. (1997). Permeability of the Blood-Brain Barrier to Circulating Free Fatty Acids. In: Yehuda, S., Mostofsky, D.I. (eds) Handbook of Essential Fatty Acid Biology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-4757-2582-7_1
Download citation
DOI: https://doi.org/10.1007/978-1-4757-2582-7_1
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-61737-017-5
Online ISBN: 978-1-4757-2582-7
eBook Packages: Springer Book Archive