Summary
A freeze-drying method has been developed by which fluorescein thiocarbamoyl dextrans (FITC-dextrans) can be localized in thin sections from nervous tissue and muscles. Labelled dextrans with molecular weights of 3,000, 20,000, 70,000 and 150,000 were injected intravenously (i.v.) into golden hamsters and samples from brain, trigeminal ganglia and sciatic nerves were examined 30 min or 4h later. For comparison experiments were also carried out in mice and some other tracers were tested as well.
The dextrans did not pass out of blood vessels in cerebral cortex and white matter. The blood vessels in the trigeminus ganglion were permeable to all of the tested compounds, i.e. even the FITC-dextran with mol. wt. 150,000. Little, if any, i.v. injected dextran could be detected in the endoneurium of sciatic nerve fascicles. Even very high concentrations of dextrans (mol. wt. 3,000 and 150,000) injected around the sciatic nerves did not penetrate the perineurium of the sciatic nerve.
As compared with other tracers dextrans have the advantage that they can be obtained in a wide range of molecular sizes. With the proposed technique presented at the end of this article they can be used for studies on vascular permeability in deep tissue like brain, ganglia and peripheral nerve. The use of these tracers will probably be particularly advantageous in investigations concerning the etiology of edematous conditions.
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References
Arvidson B (1977) Cellular uptake of exogenous horseradish peroxidase in peripheral nerve. Acta Neuropathol (Berl) 37: 35–41
Arvidson B (1979a) Distribution of intravenously injected protein tracers in peripheral ganglia of adult mice. Exp Neurol 63: 388–410
Arvidson B (1979b) Distribution of protein tracers in peripheral ganglia. Acta Univ Upsal 344: 1–72
De Belder AN, Granath K (1973) Preparation and properties of fluorescein labelled dextrans. Carbohydr Res 30: 375–378
Bienengräber A, Nagel K-H, Ernst B (1970) Speznischer Dextrannachweis durch Fluoreszenzmarkierung. Neue Ergebnisse zur Speicherung und Verteilung von Dextran im Rattenkörper. Exp Pathol (Jena) 4: 168–171
Bradbury M (1979) The concept of a blood-brain barrier. Wiley & Sons, New York
Brightman MW, Klatzo I, Olsson Y, Reese TS (1970) The blood-brain barrier to proteins under normal and pathological conditions. J Neurol Sci 10: 215–239
Chiroralia G, Salminen L, Baurman H, Kremer I (1976) Fluoresceinlabelled dextrans as tracer substance for experimental angiograms. Acta Ophthalmol (Copenh) 54: 665–667
Caulfield JP, Farquhar MG (1974) The permeability of glomerular capillaries to graded dextrans. Identification of the basement membrane as the primary filtration barrier. J Cell Biol 63: 883–903
van Deurs B (1980) Structural aspects of brain barriers, with special reference to the permeability of the cerebral endothelium and choroidal epithelium. Int Rev Cytol 65: 117–190
Falck B, Owman C (1965) A detailed methodological description of the fluorescence method for the cellular demonstration of biogenic monoamines. Acta Univ Lundens sectio II no 7: 1–52
Geisow MJ, Hart PD, Young MR (1981) Temporal changes of lysome and phagosome pH during phagolysosome formation in macrophages studies by fluorescence spectroscopy. J Cell Biol 89: 645–652
Graham RC, Karnovsky MJ (1966) The early stages of absorbtion of injected horseradish peroxidase in the proximal tubules of mouse kidney. J Histochem Cytochem 14: 291–302
Hodgman CD, Weast RC, Selby SM (1960) Handbook of chemistry and physics. Chemical Rubber Publ, Cleveland,pp 2500–2501
Hultström D, Svensjö E (1976) Simultaneous fluorescence and electron-microscopical detection of bradykinin-induced macromolecular leakage. Abstract, IXth World Conference of the European Society of Microcirculation, Antverp, Belgium
Hultström D, Svensjö E (1979) Intravital and electron microscopy study of bradykinin-induced vascular permeability changes using FITC-dextran as a tracer. J Pathol 129: 125–133
Jacobs JM, Mcfarlane RM, Cavanagh JB (1976) Vascular leakage in the dorsal root ganglia of the rat studied with horseradish peroxidase. J Neurol Sci 29: 95–107
Jonsson J, Arfors K-E, Hint HC (1970) Studies on relationships between the blood and lymphatic systems within the microcirculation. Proceedings of the 6th European Conference on Microcirculation, Aalborg. Karger, Basel pp 214–218
Lundborg G (1975) Structure and function of the intraneural microvessels as related to trauma, edema formation and nerve function. J Bone Joint Surg [Am] 57 A: 938–948
Malmgren LT, Olsson Y (1978) A sensitive method for histochemical demonstration of horseradish peroxidase in neurons following retrograde axonal transport. Brain Res 148: 279–294
Malmgren LT, Olsson Y (1980) Differences between the peripheral and the central nervous system in permeability to sodium fluorescein. J Comp Neurol 191: 103–119
Martin KH (1964) Untersuchungen über die perineurale Diffusions-barriere an gefriergetrockneten Nerven. Z Zellforsch 64:404–428
Myers, RR, Powell HC, Shapiro HM, Costello ML, Lampert PW (1980) Changes in endoneurial fluid pressure, permeability, and peripheral nerve ultrastructure in experimental lead neuropathy. Ann Neurol 8:392–402
Nakamura Y, Wayland H (1975) Macromolecular transport in the cat mesentery. Microvasc Res 9:1–21
Oldfors A (1980) Macrophages in peripheral nerves. An ultrastructural and enzyme histochemical study on rats. Acta Neuropathol (Berl) 49:43–49
Olsson Y (1968) Topographical differences in the vascular permeability of the peripheral nervous system. Acta Neuropathol (Berl) 10:26–33
Olsson Y (1971) Studies on vascular permeability in peripheral nerves. IV. Distribution of intravenously injected protein tracers in the peripheral nervous system of various species. Acta Neuropathol (Berl) 17:124–136
Olsson Y (1975) Vascular permeability in the peripheral nervous system. In: Dyck PJ, Thomas PK, Lambert EH (eds) Peripheral neuropathy, chapt. 10. Saunders, Philadelphia London Toronto
Olsson Y, Svensjö E, Arfors KE, Hultström D (1975) Fluorescein-labelled dextrans as tracers for vascular permeability studies in the nervous system. Acta Neuropathol (Berl) 33:45–50
Olsson, Y, Kristensson K (1979) Recent applications of tracer techniques to neuropathology, with particular reference to vascular permeability and axonal flow. Rec Adv Neuropathol 1:1–26
Rapoport SI (1976) Blood-brain barrier in physiology and medicine. Raven Press, New York
Salminen L, Chiroralia G, Schreiber S (1976) Distribution of intravenously injected dextrans in the posterior part of the rat eye. Proceedings of the IXth World Conference of the European Society of Microcirculation. Bibl Anat 16:69–72
Schröder U, Arfors KE, Tangen D (1976) Stability of fluorescein-labelled dextrans in vivo and in vitro. Microvasc Res 11:33
Simionescu N, Palade GE (1941) Dextrans and glycogens as particulate tracers for studying capillary permeability. J Cell Biol 50:616–624
Simionescu N, Simionescu M, Palade GE (1972) Permeability of intestinal capillaries. Pathway followed by dextrans and glycogens. J Cell Biol 53:365–392
Steinwall O, Klatzo I (1966) Selective vulnerability of the blood-brain barrier in chemically induced lesions. J Neuropathol Exp Neurol 25:542–559
Studer RK, Welch DM, Barry BA (1974) Transient alteration of the blood-brain barrier: Effect of hypertonic solutions administered via carotid artery injection. Exp Neurol 44:266–273
Svensjö E, Sharp DE, Arfors KE (1973) Leakage induced by histamine in the postcapillary venules of the hamster check pouch. Microvasc Res 6:261
Svensjö E, Arfors KE (1974) Effect of indomethacin on FITC-dextran permeability in the hamster macrovasculature. Microvasc Res 8:260
Tervo T, Joó F, Palkama A, Salminen L (1979) Penetration barrier to sodium fluorescein and fluorescein-labelled dextrans of various molecular sizes in brain capillaries. Experientia 35:252–254
Thomas PK, Olsson Y (1975) Microscopic anatomy and function of the connective tissue components of peripheral nerve. In: Dyck J, Thomas PK, Lambert EH (eds) Peripheral neuropathy, chapt 9. Saunders, Philadelphia London Toronto
Thorball N (1981) FITC-dextran tracers in microcirculatory and permeability studies using combined fluorescence stereo microscopy, fluorescence light microscopy and electron microscopy. Histochemistry 71:209–233
Tripathi RC, Tripathi BJ (1977) A new method for light- and electron-microscopic localization of fluoresceinlabelled dextran in ocular tissue using epoxy-resin embedding. Exp Eye Res 25: 259–264
Wagner FC, Stewart WB (1981) Effects of trauma on spinal cord edema. J Neurosurg 54:802–806
Watson PD, Sloop CH, Renkin EM (1976) Disappearance of fluorescein-labelled dextran from dog plasma. Biol Anat 16: 453–456
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Supported by grants from the Swedish Medical Research Council, Project 12X-03020, Eir jubileumsfond, Trygg-Hansa and Svenska livförsäkringsbolagens nämnd for medicinsk forskning. Dr. Malmgren was supported by a grant from the United States, NINCDS (1 F 32 NS 03548-1)
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Hulström, D., Malmgren, L., Gilstring, D. et al. FITC-Dextrans as tracers for macromolecular movements in the nervous system. Acta Neuropathol 59, 53–62 (1983). https://doi.org/10.1007/BF00690317
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DOI: https://doi.org/10.1007/BF00690317