Skip to main content
Log in

Penetration and removal of horseradish peroxidase injected into the cerebrospinal fluid: Role of cerebral perivascular spaces, endothelium and microglia

  • Original Investigations
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Barón, M., Gallego, A.: The relation of the microglia with the pericytes in the cat cerebral cortex. Z. Zellforsch.128, 42–57 (1972)

    Google Scholar 

  • 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)

    Google Scholar 

  • 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)

    Google Scholar 

  • 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)

    Google Scholar 

  • 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)

    Google Scholar 

  • 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

    Google Scholar 

  • 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)

    Google Scholar 

  • Cappell, D. F.: Intravitam and supravital staining. II. Blood and organs. J. Path. Bact.32, 629–675 (1929)

    Google Scholar 

  • Davidoff, M.: Über die Glia im Hypoglossuskern der Ratte nach Axotomie. Z. Zellforsch.141, 427–442 (1973)

    Google Scholar 

  • Davson, H.: Physiology of the cerebrospinal fluid. London: Churchill 1967

    Google Scholar 

  • 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)

    Google Scholar 

  • 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)

    Google Scholar 

  • 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)

    Google Scholar 

  • Hager, H.: Die feinere Cytologie und Cytopathologie des Nervensystems. Stuttgart: Fischer 1964

    Google Scholar 

  • Hager, H.: Pathologie der Makro- und Mikroglia im elektronenmikroskopischen Bild. Acta neuropath. (Berl.) Suppl.VI, 86–97 (1968)

    Google Scholar 

  • Hoffman, H. J., Olszewski, J.: Spread of sodium fluorescein in normal brain tissue. Neurology (Mineap.)11, 1081–1085 (1961)

    Google Scholar 

  • Kitamura, T.: The origin of brain macrophages—some considerations on the microglia theory of del Rio-Hortega. Acta path. jap.23, 11–26 (1973)

    Google Scholar 

  • 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)

    Google Scholar 

  • 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

    Google Scholar 

  • 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)

    Google Scholar 

  • Lee, J. C., Olszewski, J.: Penetration of radioactive bovine albumin from cerebrospinal fluid into brain tissue. Neurology (Minneap.)10, 814–822 (1960)

    Google Scholar 

  • Leonhardt, H.: Über die topographische Verteilung der subependymalen Basalmembranlabyrinthe im Ventrikelsystem des Kaninchengehirns. Z. Zellforsch.127, 392–406 (1972)

    Google Scholar 

  • 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

    Google Scholar 

  • 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)

    Google Scholar 

  • 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)

    Google Scholar 

  • 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)

    Google Scholar 

  • Mori, S., Leblond, C. P.: Identification of microglia in light and electron microscopy. J. comp. Neurol.135, 57–80 (1969)

    Google Scholar 

  • 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)

    Google Scholar 

  • 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)

    Google Scholar 

  • Pilgrim, Ch.: Altersbedingte Anhäufung von lysosomalen Residualkörpern in neurosekretorischen Zellfortsätzen. Z. Zellforsch.109, 573–582 (1970)

    Google Scholar 

  • 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)

    Google Scholar 

  • Reese, T. S., Karnovsky, M. J.: Fine structural localization of a blood-brain barrier to exogenous peroxidase. J. Cell Biol.34, 207–214 (1967)

    Google Scholar 

  • Richardson, K. C., Jarett, L., Finke, E. H.: Embedding in epoxy resins for ultrathin sectioning in electron microscopy. Stain Technol.35, 313–323 (1960)

    Google Scholar 

  • 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

    Google Scholar 

  • Schwarzberg, H., Schulz, H., Unger, H.: Hirnventrikelsystem und Liquorströmung bei Kaninchen. Acta biol. med. germ.26, 341–345 (1971)

    Google Scholar 

  • 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)

    Google Scholar 

  • 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)

    Google Scholar 

  • Srebro, Z.: Ultrastructural localization of peroxidase activity in Gomori-positive glia. Acta anat. (Basel)83, 388–397 (1972)

    Google Scholar 

  • 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)

    Google Scholar 

  • 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

    Google Scholar 

  • Vollrath, L.: Über Bau und Funktion von Basalmembranen. Dtsch. med. Wschr.93, 360–365 (1968)

    Google Scholar 

  • 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)

    Google Scholar 

  • Wolff, J.: Beiträge zur Ultrastruktur der Kapillaren in der normalen Großhirnrinde. Z. Zellforsch.60, 409–431 (1963)

    Google Scholar 

  • Woollam, D. H. M., Millen, J. W.: Perivascular spaces of the mammalian central nervous system. Biol. Rev.29, 251–283 (1954)

    Google Scholar 

  • 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)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00690695

Key words

Navigation