The blood-brain barrier to endogenous serum albumin labeled with Evans blue was studied by standard fluorescence microscopic techniques in cats. Systematic studies confirm that, except in certain well-known loci (hypothalmic median eminence, subfornical organ, area postrema, etc.), blood vessels within brain tissue are impermeable to endogenous albumin. But studies also demonstrate that in virtually all arteries at the base and over the surface of the brain and brain stem, labeled albumin passes readily through endothelium and the vascular wall to the adventitia. These observations are discussed in the context of current concepts of intracranial vascular permeability and, in terms of general biology, the possible consequences of the permeability to serum albumin of intracranial, extraparenchymal blood vessels on the composition and physiology of cerebrospinal fluid and in the pharmacokinetics of antibiotics, anticonfulsants, and antineoplastic and vasoactive agents.
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References
1.
Oldendorf WH : Overview of blood-brain barrier transport . In: Blood-brain barrier: Interface between internal medicine and the brain, Pardridge WM, moderator. Ann Int Med105:82-95, 1986.
2.
Rapoport SI: Sites and functions of the blood-brain barrier. In: Blood-Brain Barrier in Physiology and Medicine. New York : Raven Press, 1976, pp 43-86.
3.
Fishman RA: Physiology of the cerebrospinal fluid. In: Cerebrospinal Fluid in Disease of the Nervous System. Philadelphia: WB Saunders Co, 1980, pp 19-62.
4.
Broman T.: The Permeability of the Cerebrospinal Vessels in Normal and Pathological Conditions . Copenhagen: Ejnar Munksgaard , 1949, pp 17-19.
5.
Steinwall 0, Klatzo I: Selective vulnerability of the blood-brain barrier to chemically induced lesions. J Neuropath Exp Neurol25:542-549, 1966.
6.
Heck AF, Hasuo M., Furuse M., et al: Distribution of serum protein labeled with Evans blue in the walls of extra- and intracranial blood vessels of the cat. Atherosclerosis23:227-238, 1976.
7.
Heck AF, Kretschmann HJ, Zilles K., et al: Weight, volume and specific gravity of the cat brain: Effects of experimental procedure and formalin fixation. Stroke6:232, 1975.
8.
Reinoso-Suarez F.: Topagraphischer Himatlas der Katze fur experimental-physiologische Untersuchungen . Darmstadt: E Merck A.G., 1961.
9.
Kretschman HJ : Fluoreszenz-polarisationmikroskopische Analyse der Urtrastruktur von Elasticalamellen und Elasticafasem. Z Zellforsch60:7-68, 1963.
10.
Klatzo I., Miquel J., Otenasek R.: The application of fluorescein labeled serum proteins (FLSP) to the study of vascular permeability of the brain. Acta Neuropath2:144-160, 1962.
11.
Friedman M. , Byers SA: Endothelial permeability in atherosclerosis . Arch Path76:99-105, 1963.
12.
McGill HC, Greer JC, Holman RL: Sites of vascular vulnerability in dogs demonstrated by Evans blue . Arch Path64:303-311, 1957.
13.
Adams Cwm, Tugan NA: Elastic degeneration as a source of lipids in the early lesion of atherosclerosis . J Path Bact82:131-139, 1961.
14.
Rawson RA: The binding of T-1824 and structurally related diazo dyes by the plasma proteins . Am J Physiol138:708-717, 1942-43.
15.
Markus G., Baumberger JP: A polarigraphic study of Evans blue and its combination with plasma proteins . J Biol Chem206:59-65, 1959.
16.
Windholz M (ed): Merck Index, ed. 10, Rahway, NJ: Merck & Co Inc, 1983, pp 33, 564.
17.
Altman PL, Dittmer DS (eds): Blood and Other Body Fluids. Bethesda, Md: Fed Am Soc Exp Biol, 1971 , pp 3, 59.
18.
Westergaard E., Brightman MW: Transport of proteins across normal cerebral arterioles. J ComparNeurol152:17-44, 1973.
19.
Fishman RA: Cerebrospinal Fluid in Diseases of the Nervous System. Philadelphia: WB Saunders Co, 1980 , pp 205, 206.
20.
Pardridge WM : Carrier-mediated transport of thyroid hormones through the rat blood-brain barrier: Primary role of albumin-bound hormone . Endocrinology105:605-612, 1979.
21.
Pardridge WM , Landaco EM: Tracer kinetic model of blood-brain barrier transport of plasma protein-bound ligands. J Clin Invest74:745-752, 1984.
22.
Pardridge WM : Misconceptions about the blood-brain barrier . In: Blood-brain barrier: Interface between internal medicine and the brain, Pardridge WM, moderator. Ann Intern Med105:82-95, 1986.
23.
Pardridge WM , Mietus LJ: Transport of steroid hormones through the rat blood-brain barrier. J Clin Invest64:145-154, 1979.
24.
Schaltenbrand G., Putnam T.: Untersuchungen zum Kreislauf des Liquor cerebrospinalis mit Hilfe intravenoser Fluorescinein Sprinzungen. Deut Z Nervenheilk96:923-132, 1927.
25.
Rapoport SI: Permeability and osmotic properties of the blood-brain barrier; pathological alterations of the blood-brain barrier. In: Blood-Brain Barrier in Physiology and Medicine. New York: Raven Press, 1976, pp 87-152.
26.
Watanabe M. , Rosenblum WI: In vivo studies of pial vascular permeability to sodium fluorescein. Stroke18:1157-1159, 1987.
27.
Unterberg A. , Wahl M., Baethmann A., et al: Studies of pial vascular permeability (letter to the editor and response). Stroke19:1306-1307, 1988.
28.
Rapoport SI: Regulation of drug entry into the nervous system. In: Blood-Brain Barrier in Physiology and Medicine. New York : Raven Press, 1976, pp 153-176.
29.
Koch-Weser J., Sellers EM: Binding of drugs to serum albumin . N Engl J Med294:311-3216, 526-531, 1976.
30.
Cornford EM , Pardridge WM, Braun LD, et al: Increased blood-brain barrier transport of protein-bound anticonsulvant drugs in the newborn. J Cereb Blood Flow Metab3:280-286, 1983.
