Summary
The distribution of horseradish peroxidase (HRP) in hypothalamic and cortical brain tissues was studied at different time intervals after injection into the lateral ventricle of adult Wistar rats. A preferential penetration of the tracer was found along the perivascular spaces of blood vessels. Their importance for the exchange between CSF and extracellular space of the brain is discussed. It is suggested that the preferential penetration route extends beyond the range of the Virchow-Robin space down to the level of the capillaries.
Although the intercellular clefts between endothelial cells are sealed by tight junctions there is a retrograde vesicular transport of the tracer to the blood stream which contributes to the removal of HRP from the brain tissue. This indicates that in this case one has to distinguish between a blood-brain barrier and a brain-blood barrier.
One of the main factors in the removal and degradation of the foreign protein is shown to be the perivascular microglia the identity of which is readily established by comparing its appearance in the light and electron microscope.
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References
Barón, M., Gallego, A.: The relation of the microglia with the pericytes in the cat cerebral cortex. Z. Zellforsch.128, 42–57 (1972)
Becker, N. H., Almazan, R.: Evidence for the functional polarization of micropinocytotic vesicles in the rat choroid plexus. J. Histochem. Cytochem.16, 278–280 (1968)
Becker, N. H., Hirano, A., Zimmerman, H. M.: Observations of the distribution of exogenous peroxidase in the rat cerebrum. J. Neuropath. exp. Neurol.27, 439–452 (1968)
Blinzinger, K.: Elektronenmikroskopische Beobachtungen bei experimentell erzeugter Randzonensiderose des Kaninchengehirns. Acta neuropath. (Berl.) Suppl. IV, 146–157 (1968)
Blinzinger, K., Hager, H.: Elektronenmikroskopische Untersuchungen über die Feinstruktur ruhender und progressiver Mikrogliazellen im Säugetiergehirn. Beitr. path. Anat.127, 173–192 (1962)
Brightman, M. W.: The distribution within the brain of ferritin injected into cerebrospinal fluid compartments. II. Parenchymal distribution. Amer. J. Anat.117, 193–219 (1965)
Brightman, M. W., Reese, T. S., Feder, N.: Assessment with the electronmicroscope of the permeability to peroxidase of cerebral endothelium and epithelium in mice and sharks. In: C. Crone and N. A. Lassen, eds.: Capillary permeability, pp. 468–476. Copenhagen: Munksgaard 1970
Cancilla, P. A., Baker, R. N., Pollok, P. S., Frommes, S. P.: The reaction of pericytes of the central nervous system to exogenous protein. Lab. Invest.26, 376–383 (1972)
Cappell, D. F.: Intravitam and supravital staining. II. Blood and organs. J. Path. Bact.32, 629–675 (1929)
Davidoff, M.: Über die Glia im Hypoglossuskern der Ratte nach Axotomie. Z. Zellforsch.141, 427–442 (1973)
Davson, H.: Physiology of the cerebrospinal fluid. London: Churchill 1967
Dempsey, E. W., Wislocki, G. B.: An electron microscopic study of the blood-brain barrier in the rat, employing silver nitrate as a vital stain. J. biophys. biochem. Cytol.1, 245–256 (1955)
Eberhardt, H. G.: Supravitale Farbstoffversuche zur Frage der Stoffverteilung im ZNS der Ratte, besonders im Hypothalamus und Infundibulum. Z. mikr.-anat. Forsch.83, 525–534 (1971)
Graham, R. C., Karnovsky, M. J.: The early stages of absorption of injected horseradish peroxidase in the proximal tubules of mouse kidney: Ultrastructural cytochemistry by a new technique. J. Histochem. Cytochem.14, 291–301 (1966)
Hager, H.: Die feinere Cytologie und Cytopathologie des Nervensystems. Stuttgart: Fischer 1964
Hager, H.: Pathologie der Makro- und Mikroglia im elektronenmikroskopischen Bild. Acta neuropath. (Berl.) Suppl.VI, 86–97 (1968)
Hoffman, H. J., Olszewski, J.: Spread of sodium fluorescein in normal brain tissue. Neurology (Mineap.)11, 1081–1085 (1961)
Kitamura, T.: The origin of brain macrophages—some considerations on the microglia theory of del Rio-Hortega. Acta path. jap.23, 11–26 (1973)
Klatzo, I., Miquel, J., Otenasek, R.: The application of fluorescein labeled serum proteins (FLSP) to the study of vascular permeability in the brain. Acta neuropath. (Berl.)2, 144–160 (1962)
Klatzo, I., Wiśniewski, H., Smith, D. E.: Observations on penetration of serum proteins into the central nervous system. In: E. D. P. De Robertis and R. Carrea, eds.: Biology of Neuroglia. Progr. in Brain Res., Vol. 15, pp. 73–88. Amsterdam-London-New York: Elsevier 1965
Kubie, L. S.: A study of the perivascular tissues of the central nervous system, with the supravital technique. J. exp. Med.46, 615–626 (1927)
Lee, J. C., Olszewski, J.: Penetration of radioactive bovine albumin from cerebrospinal fluid into brain tissue. Neurology (Minneap.)10, 814–822 (1960)
Leonhardt, H.: Über die topographische Verteilung der subependymalen Basalmembranlabyrinthe im Ventrikelsystem des Kaninchengehirns. Z. Zellforsch.127, 392–406 (1972)
Luse, S.: Microglia. In: J. Minckler, ed.: Pathology of the nervous system, pp. 531–538, Vol. 1. New York-Toronto-Sydney-London: Mc Graw-Hill Book Co. 1968
Mandelstamm, M., Krylow, L.: Vergleichende Untersuchungen über die Farbenspeicherung im Zentralnervensystem bei Injektionen der Farbe ins Blut und in den Liquor cerebrospinalis. II. Mitteilung. Z. ges. ex. Med.60, 63–85 (1928)
Matthews, M. A., Kruger, L.: Electron microscopy of non neuronal cellular changes accompanying neuronal degeneration in thalamic nuclei of the rabbit. I. Reactive hematogenous and perivascular elements within the basal lamina. J. comp. Neurol.148, 285–311 (1973a)
Matthews, M. A., Kruger, L.: Electron microscopy of non neuronal cellular changes accompanying neuronal degeneration in thalamic nuclei of the rabbit. II. Reactive elements within the neuropil. J. comp. Neurol.148, 313–345 (1973b)
Mori, S., Leblond, C. P.: Identification of microglia in light and electron microscopy. J. comp. Neurol.135, 57–80 (1969)
Nelson, E., Blinzinger, K., Hager, K.: Electron microscopic observations on subarachnoid and perivascular spaces of the Syrian hamster brain. Neurology (Minneap.)11, 285–295 (1961)
Oehmichen, M., Groninger, H., Saebisch, R., Narita, Y.: Mikroglia und Perizyten als Transformationsformen der Blutmonozyten mit erhaltener Proliferationstätigkeit. Acta neuropath. (Berl.)23, 200–218 (1973)
Pilgrim, Ch.: Altersbedingte Anhäufung von lysosomalen Residualkörpern in neurosekretorischen Zellfortsätzen. Z. Zellforsch.109, 573–582 (1970)
Pilgrim, Ch., Wagner, H.-J., Brandl, J.: Uptake and transport of horseradish peroxidase (HRP) in the hypothalamo-neurohypophysial system of rats. Proc. VI Int. Symp. on Neurosecretion, London 1973
Reese, T. S., Brightman, M. W.: Similarity in structure and permeability to peroxidase of epithelia overlying fenestrated cerebral capillaries. Anat. Rec.160, 414 (1968)
Reese, T. S., Karnovsky, M. J.: Fine structural localization of a blood-brain barrier to exogenous peroxidase. J. Cell Biol.34, 207–214 (1967)
Richardson, K. C., Jarett, L., Finke, E. H.: Embedding in epoxy resins for ultrathin sectioning in electron microscopy. Stain Technol.35, 313–323 (1960)
Schaltenbrand, G.: Plexus und Meningen. In: W. Bargmann, ed.: Handb. mikr. Anat. d. Menschen, Vol. IV/2, pp. 1–139. Berlin-Göttingen-Heidelberg: Springer 1955
Schwarzberg, H., Schulz, H., Unger, H.: Hirnventrikelsystem und Liquorströmung bei Kaninchen. Acta biol. med. germ.26, 341–345 (1971)
Shimoda, A.: Elektronenmikroskopische Untersuchungen über den perivasculären Aufbau des Gehirns unter Berücksichtigung der Veränderungen bei Hirnödem und Hirnschwellung. Dtsch. Z. Nervenheilk.183, 78–98 (1961)
Spatz, H.: Die Bedeutung der vitalen Färbung für die Lehre vom Stoffaustausch zwischen dem Zentralnervensystem und dem übrigen Körper. Arch. Psychiat. (Nervenkr.)101, 267–358 (1934)
Srebro, Z.: Ultrastructural localization of peroxidase activity in Gomori-positive glia. Acta anat. (Basel)83, 388–397 (1972)
Srebro, Z., Cichocki, T.: A system of periventricular glia in brain characterized by large peroxisome-like cell organelles. Acta histochem. (Berl.)41, 108–114 (1971)
Vaughn, J. E., Skoff, R. P.: Neuroglia in experimentally altered central nervous system. In: G. H. Bourne, ed.: The structure and function of nervous tissue, Volume V, pp. 39–72. New York-London: Academic Press 1972
Vollrath, L.: Über Bau und Funktion von Basalmembranen. Dtsch. med. Wschr.93, 360–365 (1968)
Wislocki, G. B., Leduc, E. H.: Vital staining of the hematoencephalic barrier by silver nitrate and trypan blue, and cytological comparisons of the neurohypophysis, pineal body, area postrema, intercolumnar tubercle and supraoptic crest. J. comp. Neurol.96, 371–412 (1952)
Wolff, J.: Beiträge zur Ultrastruktur der Kapillaren in der normalen Großhirnrinde. Z. Zellforsch.60, 409–431 (1963)
Woollam, D. H. M., Millen, J. W.: Perivascular spaces of the mammalian central nervous system. Biol. Rev.29, 251–283 (1954)
Woollam, D. H. M., Millen, J. W.: The perivascular spaces of the mammalian central nervous system and their relation to the perineuronal and subarachnoid spaces. J. Anat. (Lond.)89, 193–200 (1955)
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Wagner, H.J., Pilgrim, C. & Brandl, J. Penetration and removal of horseradish peroxidase injected into the cerebrospinal fluid: Role of cerebral perivascular spaces, endothelium and microglia. Acta Neuropathol 27, 299–315 (1974). https://doi.org/10.1007/BF00690695
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DOI: https://doi.org/10.1007/BF00690695