Skip to main content
SpringerLink
Log in

Cerebrovascular ultrastructural alterations after intra-arterial infusions of ouabain, scilla-glycosides, heparin and histamine

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

Summary

Cardiac glycosides which inhibit Na/K-ATPase (ouabain, scilliroside, scillirosidin) as well as heparin and histamine were infused into a cannulated branch of the middle cerebral artery or by isolated head perfusion in cats and dogs.

Ouabain permeating the blood-brain barrier (BBB) caused the same selective swelling of astrocytes and of certain presynaptic elements as after direct application to the brain tissue. The other cellular elements of brain tissue and the vascular endothelium did not react, although the latter was exposed to the highest drug concentrations (about 10−3 M ouabain). By the swelling about one third of the capillaries became more or less constricted accompanied by an increase in endothelial vesiculation and in the number of osmiophilic inclusions in all cells of the vascular wall and of the pericapillary tissue. Osmiophilic material resembling plasma proteins occurred in widened intercellular clefts indicating an increased BBB permeability after survival times (40 min). In contrast to the capillaries some terminal vessels are dilated which may correspond to shunt vessels causing an inhomogeneous, even increased cerebral blood flow after ouabain.

Scilliroside and scillirosidin cause essentially the same changes as ouabain, but of smaller intensity and extent. In the present study, neither histamine nor heparin caused any structural change of the vessels or brain tissue.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Alksne, J. F.: The passage of colloidal particles across the dermal capillary wall under the influence of histamine. Quart. J. exp. Physiol.44, 51–66 (1959)

    Google Scholar 

  • Bakay, L., Lee, J. C.: Cerebral edema. Springfield, Ill.: Ch. C. Thomas 1965

    Google Scholar 

  • Bakay, L.: Changes in barrier effect in pathological states. Progr. Brain Res.29, 315–341 (1968)

    Google Scholar 

  • Baldy-Moulinier, M.: Cerebral blood flow and membrane ionic pump. Europ. Neurol.6, 107 to 113 (1971/72)

    Google Scholar 

  • Basu Ray, B. N., Booker, W. M., Dutta, S. N.: Effects of microinjection of ouabain into the hypothalamus in cats. Brit. J. Pharmacol.45, 197–207 (1972)

    Google Scholar 

  • Boardman, L. J., Lamb, J. F., McCall, D.: Uptake of (3H) ouabain and Na pump turnover rates in cells cultured in ouabain. J. Physiol. (Lond.)225, 619–636 (1972)

    Google Scholar 

  • Brightman, M. W., Klatzo, I., Olsson, Y., Reese, T. S.: The blood-brain barrier to proteins under normal and pathological conditions. J. neurol. Sci.10, 215–239 (1970)

    Google Scholar 

  • Cancilla, P. A., Baker, R. N., Pollock, P. S.: The reaction pericytes of the central nervous system to exogenous protein. Lab. Invest.26, 376–383 (1972)

    Google Scholar 

  • Chiang, J., Kowada, M., Ames, A. III., Wright, R. L., Majno, G.: Cerebral ischemia. III. Vascular changes. Amer. J. Path.52, 455–476 (1968)

    Google Scholar 

  • Clawson, C. C., Hartmann, J. F., Vernier, R. L.: Electron microscopy of the effect of gram negative endotoxin on the blood-brain barrier. J. comp. Neurol.127, 183–197 (1966)

    Google Scholar 

  • Cornog, J. L., Jr., Gonatas, N. K., Freierman, J. R.: Effects of intracerebral injection of ouabain on the fine structure of rat cerebral cortex. Amer. J. Path.51, 672–690 (1967)

    Google Scholar 

  • Cummins, J., Hydén, H.: Adenosine triphosphate levels and adenosine triphosphatase in neurons, glia and neuronal membranes of the vestibular nucleus. Biochim. biophys. Acta (Amst.)60, 271–283 (1962)

    Google Scholar 

  • Dhopeshwarkar, G. A., Subramanian, C.: Fatty acid transport into the brain (BBA 75831). Biochim. biophys. Acta (Amst.)255, 572–581 (1972)

    Google Scholar 

  • Drommer, W.: Feinstrukturelle Alterationen an den Capillaren und Venulen im zentralen Nervensystem des Schweins nach experimentellem Colitoxinschock. Acta neuropath. (Berl.)22, 13–29 (1972)

    Google Scholar 

  • Eidelberg, E., Fishman, J., Hams, M. L.: Penetration of sugars across the blood-brain barrier. J. Physiol. (Lond.)191, 47–57 (1967)

    Google Scholar 

  • Eklöf, B., McMillan, V., Siesjö, B. K.: The effect of ischemia upon the energy state of the brain. Europ. Neurol.6, 60–65 (1971/72)

    Google Scholar 

  • Emmenegger, H., Taeschler, M., Cerletti, A.: Neue Möglichkeit der isolierten Hirndurch-strömung. Helv. physiol. pharmacol. Acta21, 239–244 (1963)

    Google Scholar 

  • Friede, R. L., Hu, K. H., Cechner, R.: Glial footplates in the bowfin. II. Effects of ouabain and selective damage to footplates on electrolyte composition, glycogen content, fine structure and electrophysiology of bowfin brain incubated in vitro. J. Neuropath. exp. Neurol.28, 540–570 (1969)

    Google Scholar 

  • Gabbiani, G., Badonnel, M. C., Majno, G.: Intra-arterial injections of histamine, serotonin or bradykinin: A topographic study of vascular leakage. Proc. Soc. exp. Biol. (N. Y.)135, 447–452 (1970)

    Google Scholar 

  • Giardini, V., Cartoni, C., Carpi, A.: Quantitative relationship between CSF pressure changes and CBF changes caused by vasoactive agents. Europ. Neurol.8, 69–73 (1972)

    Google Scholar 

  • Goldstein, M., Ohi, Y., Backstrom, T.: The effect of ouabain on catecholamine biosynthesis in rat brain cortex slices. J. Pharmacol. exp. Ther.174, 77–85 (1970)

    Google Scholar 

  • Gonatas, N. K., Levine, S., Shoulson, R.: Electron microscopic investigation of phagocytosis of myelin in an experimental leukoencephalopathy. Ann. N. Y. Acad. Sci.122, 6–14 (1964)

    Google Scholar 

  • Hodges, P. C., Sellers, R. D., Story, J., Stanley, P. H., Torres, F., Lillehei, C. W.: The effects of total cardiopulmonary bypass procedures upon cerebral function evaluated by the electroencephalogram and blood-brain barrier test; a clinical and experimental investigation, pp. 279–294. In: J. G. Allen (Ed.): Extracorporal circulation. Springfield, Ill.: Ch. C. Thomas 1958

    Google Scholar 

  • Jóo, F.: Increased production of coated vesicles in the brain capillaries during enhanced permeability of the blood-brain barrier. Brit. J. exp. Path.52, 646–649 (1971)

    Google Scholar 

  • Karnovsky, M. J.: The transfer of molecules and ions between capillary blood and tissue. In: Crone and Lassen: Capillary permeability. Alfred Benzon Foundation Symposium II. Kopenhagen: Munsgaard 1970

    Google Scholar 

  • Kelentey, B., Földes, I., Lipák, J., Csongor, J.: Effect of heparin on the blood, brain, cerebrospinal fluid and vitreous humor barriers. Arch. int. Pharmacodyn.150, 363–371 (1964)

    Google Scholar 

  • Klatzo, I., Miquel, J., Otenasek, R.: The application of fluorescein labelled serum proteins (FLSP) to the study of vascular permeability in the brain. Acta neuropath. (Berl.)2, 144–160 (1962)

    Google Scholar 

  • Liebaldt, G.: Tierexperimentelle Untersuchungen zur Permeabilitätswirksamkeit moderner Arzneimittel (Psychopharmaka und Antikoagulantien). Arzneimittel-Forsch.15, 1056 to 1060 (1965)

    Google Scholar 

  • Majno, G., Shea, S. M., Leventhal, M.: Endothelial contraction induced by histamine type mediators. J. Cell Biol.42, 647–672 (1969)

    Google Scholar 

  • Manz, H. J., Robertson, D. M.: Vascular permeability to horseradish peroxidase in brain stem lesions of thiamine-deficient rats. Amer. J. Path.66, 565–572 (1972)

    Google Scholar 

  • Meier-Ruge, W., Gygax, P., Iwangoff, P., Schieweck, Ch., Wolff, J. R.: The significance of pericapillary astroglia for cerebral cortical blood flow and ECoG activity. An investigation of ouabain, as an Na+/K+-ATPase inhibitor. In: Pathology of Cerebral Microcirculation, pp. 235–243. J. Cervós-Navarro (Ed.). Berlin: W. de Gruyter 1974

    Google Scholar 

  • Musilowa, H., Schieweck, Ch., Iwangoff, P., Chappuis, A., Enz, A.: The effect of scillirosidin on the Na+/K+-ATPase of the cat brain in vitro and in vivo. Experientia (Basel)29, 763 (1973)

    Google Scholar 

  • Noack, W., Wolff, J. R., Güldner, F.-H., Moritz, A.: Über die akuten Veränderungen im Parietalcortex der Ratte nach spitzem Trauma. Acta neuropath. (Berl.)19, 249–264 (1971)

    Google Scholar 

  • Orlowski, M., Sessa, G., Green, J. P.: y-glutamyl-transpeptidase in brain capillaries: Possible site of a blood-brain barrier for amino acids. Science184, 66–68 (1974)

    Google Scholar 

  • Pappas, G. D.: Some morphological considerations of the blood-brain barrier. J. neurol. Sci.10, 241–246 (1970)

    Google Scholar 

  • Pentschew, A.: Probleme der Permeabilitätspathologie im Gehirn. Acta psychiat. (Kbh.)185, 345–369 (1950)

    Google Scholar 

  • Prince, D. A., Lux, H. D., Neher, E.: Measurement of extracellular potassium activity in cat cortex. Brain Res.50, 489–495 (1973)

    Google Scholar 

  • Prosenz, P., Reinmuth, O. M., Scheinberg, P.: Experimental evidence of a different mode of action of hypercapnia and hypoxia on cerebral vessels. Europ. Neurol.6, 119–122 (1971/72)

    Google Scholar 

  • Raaflaub, J.: Über die Beziehungen zwischen der Lipidlöslichkeit von Pharmaka und ihrem pharmakokinetischen Verhalten. Experientia (Basel)26, 457–467 (1970)

    Google Scholar 

  • Reese, T. S., Karnovsky, M. J.: Fine structural localization of a blood-brain barrier to exogenous peroxidase. J. Cell Biol.34, 207–217 (1967)

    Google Scholar 

  • Renkawek, K., Palladini, G., Ieradi, L. A.: Morphologie de la glie cultivée in vitro après l'ouabaine. In: Proc. 6th Intern. Congr. Neuropath., Paris 1970, pp. 458–459. Paris: Masson & Cie 1970

    Google Scholar 

  • Schieweck, Ch., Wolff, J. R., Meier-Ruge, W., Bangerter, D.: Technique for cannulating a branch of the middle cerebral artery of the cat and dog for studying direct drug effects on the brain and the blood-brain barrier. (In press)

  • Selwood, L.: Electron microscopy of endocytic elements in the cat cerebrum. Acta neuropath. (Berl.)18, 299–310 (1971)

    Google Scholar 

  • Siesjö, B. K.: Metabolism and flow in the hypoxic brain. Europ. Neurol.6, 43–48 (1971/72)

    Google Scholar 

  • Skou, J. S.: Enzymatic basis for active transport of Na+ and K+ across cell membrane. Physiol. Rev.45, 596–617 (1965)

    Google Scholar 

  • Stefanelli, A., Palladini, G., Ieradi, L.: Effectto della ouabaina sul tessuto nervoso in coltura in vitro. Experientia (Basel)21, 717–719 (1965)

    Google Scholar 

  • Swanson, P. D., McIlwain, H.: Inhibition of the sodium-ion-stimulated adenosine triphosphatase after treatment of isolated guinea pig cerebral cortex with ouabain and other agents. J. Neurochem.12, 877–891 (1965)

    Google Scholar 

  • Tower, D. B.: Ouabain and the distribution of calcium and magnesium in cerebral tissues in vitro. Exp. Brain Res.6, 273–283 (1968)

    Google Scholar 

  • Tschirgi, R. D.: Blood-brain barrier. In: Biology of Mental Health and Disease, pp. 34–46. New York: Hoeber 1952

    Google Scholar 

  • Vegge, T.: A blood-aqueous barrier to small molecules in the ciliary processes of the velvet monkey (Cercopithecus aethiops). Z. Zellforsch.135, 483–500 (1972)

    Google Scholar 

  • Venturini, G., Palladini, G.: ATPase activity, sodium and potassium content in Guinea pig cortex after ouabain treatment in vitro. J. Neurochem.20, 237–239 (1973)

    Google Scholar 

  • Whetsell, W., Bunge, R.: Reversible vacuole formation in the Golgi region of neurons treated with an inhibitor of sodium-potassium-activated ATPase. J. Cell Biol.39, 141a (1968)

    Google Scholar 

  • Whittam, R., Wheeler, K. P.: Transport across cell membranes. Ann. Rev. Physiol.32, 21–60 (1970)

    Google Scholar 

  • Wolff, J. R.: Über die Möglichkeiten der Kapillarverengung im Zentralnervensystem. Eine elektronenmikroskopische Studie an der Großhirnrinde des Kaninchens. Z. Zellforsch.63, 593–611 (1964)

    Google Scholar 

  • Wolff, J. R.: Quantitative aspects of astroglia. In: Proc. VI Int. Congr. Neuropath., Paris 1970, pp. 327–353. Paris: Masson & Cie. 1970

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Basic Medical Research, Sandoz Ltd., Basle, Switzerland

    J. R. Wolff, Ch. Schieweck, H. Emmenegger & W. Meier-Ruge

  2. Max-Plank-Institut für Biophysikalische Chemie, Am Fassberg, D-3400, Göttingen, Germany

    J. R. Wolff

Authors
  1. J. R. Wolff
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ch. Schieweck
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. Emmenegger
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. W. Meier-Ruge
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wolff, J.R., Schieweck, C., Emmenegger, H. et al. Cerebrovascular ultrastructural alterations after intra-arterial infusions of ouabain, scilla-glycosides, heparin and histamine. Acta Neuropathol 31, 45–58 (1975). https://doi.org/10.1007/BF00696886

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00696886

Key words

Search

Navigation