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Acta Neuropathologica

, Volume 69, Issue 1–2, pp 1–16 | Cite as

The blood-brain barrier to horseradish peroxidase at the onset of bicuculline-induced seizures in hypothalamus, pallidum, hippocampus, and other selected regions of the rabbit

  • C. Nitsch
  • G. Goping
  • H. Laursen
  • I. Klatzo
Original Works

Summary

Rabbits were subjected to bicuculline-induced generalized seizures of 15-min duration to elucidate the mechanism by which the macromolecule horseradish peroxidase (HRP) traverses the blood-brain barrier (BBB) in specific brain areas. Transendothelial pinocytosis at the level of arterioles was the main route of passage. In addition, in thalamus and hippocampus pinocytotic vesicles were observed in capillaries. In thalamus, hypothalamus and septum vesicles in the endothelium of venules were also present. Repeatedly, pinocytotic vesicles were ejecting their content into the interendothelial clefts, so that the presence of HRP reaction product between adjacent tight junctions cannot be considered a conclusive evidence for their opening.

The HRP, which had reached the neuropil due to the seizure-evoked BBB opening, accumulated in the interstitial spaces and penetrated the synaptic cleft. Uptake of the tracer in vesicular form into presynaptic boutons, presumably excitatory ones as diagnosed by their ultrastructural features, was observed in all brain regions. The uptake was rare in septum, periaqueductal gray, hypothalamus, and cerebellar cortex; frequent in pallidum, hippocampus, and medulla oblongata; and very intense in thalamus. Uptake in postsynaptic dendrites was present mostly in the vicinity of boutons. Incorporation into glial processes was rare and confined to perivascular astrocytes.

It is suggested, that HRP traverses the BBB by regionally selective, transmitter-controlled pinocytotic transport and that the neuronal uptake of the foreign protein is at least partially dependent on the involvement of synapses of particular brain regions in the paroxysmal activity during the generalized seizures.

Key words

Blood-brain barrier Epileptic seizures Pinocytosis Hypothalamus Pallidum Hippocampus Septum Thalamus Periaque-ductal gray Cerebellar cortex 

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References

  1. Bolwig TG, Hertz MM, Westergaard E (1977) Acute hypertension causing blood-brain barrier breakdown during epileptic seizures. Acta Neurol Scand 56:335–342Google Scholar
  2. Brightman MW, Klatzo I, Olsson Y, Reese TS (1970) The blood-brain barrier to proteins under normal and pathological conditions. J Neurol Sci 10:215–239Google Scholar
  3. Brightman MW, Hori M, Rapoport SI, Reese TS, Westergaard E (1973) Osmotic opening of tight junctions in cerebral endothelium. J Comp Neurol 52:317–326Google Scholar
  4. Broadwell RD, Brightman MW (1979) Cytochemistry of undamaged neurons transporting exogenous protein in vivo. J Comp Neurol 185:31–74Google Scholar
  5. Curtis DR, Duggan AW, Felix D, Johnston GAR (1971) Bicuculline, an antagonist of GABA and synaptic inhibition in the spinal cord of the cat. Brain Res 32:69–96Google Scholar
  6. Diemer NH, von Lubitz DKJE (1983) Cerebral ischaemia in the rat: increased permeability of post-synaptic membranes to horseradish peroxidase in the early postischaemic period. Neuropathol Appl Neurobiol 9:403–414Google Scholar
  7. Domer FR, Boertje SB, Bing EG, Reddix I (1983) Histamine-and acetylcholine-induced changes in the permeability of the blood-brain barrier of normotensive and spontaneously hypertensive rats. Neuropharmacology 22:615–619Google Scholar
  8. Dux E, Joó F (1982) Effects of histamine on brain capillaries. Exp Brain Res 47:252–258Google Scholar
  9. Edvinsson L, Hardebo JE, Owman C (1978) Pharmacological analysis of 5-hydroxytryptamine receptors in isolated intracranial and extracranial vessels of cat and man. Circ Res 42:143–151Google Scholar
  10. Edvinsson L, Högestätt ED, Uddman R, Auer LM (1983) Cerebral veins: Fluorescence histochemistry, electron microscopy, and in vitro reactivity. J Cereb Blood Flow Metab 3:226–230Google Scholar
  11. Evans JA, Liscum L, Hood DC, Holtzman E (1981) Uptake of horseradish peroxidase by presynaptic terminals of bipolar cells and photoreceptors of the frog retina. J Histochem Cytochem 29:511–518Google Scholar
  12. Grammas P, Diglio CA, Marks BH, Giacomelli F, Wiener J (1983) Identification of muscarinic receptors in rat cerebral cortical microvessels. J Neurochem 40:645–651Google Scholar
  13. Harik SI, Sharma VK, Weatherbe JR, Warren RH, Banergee SP (1980) Adrenergic receptors of cerebral microvessels. Eur J Pharmacol 61:207–209Google Scholar
  14. Hedley-Whyte ET, Lorenzo AV, Hsu DW (1977) Protein transport across cerebral vessels during metrazole-induced convulsions. Am J Physiol 233:C74–C85Google Scholar
  15. Huang M, Rorstad OP (1983) Effects of vasoactive intestinal polypeptide, monoamines, prostaglandins, and 2-chloroadenosine on adenylate cyclase in rat cerebral microvessels. J Neurochem 40:719–726Google Scholar
  16. Johansson B, Nilsson B (1977) The pathophysiology of the blood-brain barrier dysfunction induced by severe hypercapnia and by epileptic brain activity. Acta Neuropathol (Berl) 38:153–158Google Scholar
  17. Joó F (1972) Effect of N6O2-dibutyryl cyclic 3′,5′-adenosine monophosphate on the pinocytosis of brain capillaries of mice. Experientia 28:1470–1471Google Scholar
  18. Joó F, Rakonczay Z, Wollemann M (1975) cAMP-mediated regulation of the permeability in the brain capillaries. Experientia 31:582–584Google Scholar
  19. Kurnushina IL, Palacios JM, Barbin G, Dux E, Joó F, Schwarz JC (1980) Studies on capillary-rich fraction isolated from brain. Histaminic components and characterization of the histamine receptors linked to adenylate cyclase. J Neurochem 34:1201–1208Google Scholar
  20. Krause DN, Wong E, Degener P, Roberts E (1980) GABA receptors in bovine cerebral blood vessels: binding studies with3H-muscimol. Brain Res 185:51–57Google Scholar
  21. Lange W, Halata Z (1979) Comparative studies on the pre- and post-terminal blood vessels in the cerebellar cortex of rhesus monkey, cat, and rat. Anat Embryol 158:51–62Google Scholar
  22. Laursen H, Westergaard E (1977) Enhanced permeability to horseradish peroxidase across cerebral vessels in the rat after portocaval anastomosis. Neuropathol Appl Neurobiol 3:29–43Google Scholar
  23. LaVail JH, LaVail MM (1974) The retrograde intra-axonal transport of horseradish peroxidase in the chick visual system: A light- and electron-microscopic study. J Comp Neurol 157:303–358Google Scholar
  24. Lehtosalo J, Panula P, Laitinen LA (1982) The permeability alteration of brain and spinal cord vasculature to horseradish peroxidase during experimental decompression sickness as compared to the alteration in permeability induced by hyperosmolar solution. Acta Neuropathol (Berl) 57:179–187Google Scholar
  25. Nagy Z, Mathieson G, Hüttner I (1979) Blood-brain barrier opening to horseradish peroxidase in acute arterial hypertension. Acta Neuropathol (Berl) 48:45–53Google Scholar
  26. Nauta HJW, Kaiserman-Abramof IR, Lasek RJ (1975) Electron-microscopic observations of horseradish peroxidase transported from the caudoputamen to the substantia nigra in the rat: possible involvement of the agranular reticulum. Brain Res 85:373–384Google Scholar
  27. Nitsch C, Klatzo I (1983) Regional patterns of blood-brain barrier breakdown during epileptiform seizures induced by various convulsive agents. J Neurol Sci 59:305–322Google Scholar
  28. Nitsch C, Rinne U (1981) Large dense-core vesicle exocytosis and membrane recycling in the mossy fibre synapses of the rabbit hippocampus during epileptiform seizures. J Neurocytol 10:201–219Google Scholar
  29. Nitsch C, Suzuki R, Fujiwara K, Klatzo I (1985) Incongruence of regional cerebral blood flow and blood-brain barrier opening in rabbits at the onset of seizures induced by bicuculline, methoxypyridoxine, and kainic acid. J Neurol Sci 67:67–79Google Scholar
  30. Petito CK, Levy DE (1980) The importance of cerebral arterioles in alterations of the blood-brain barrier. Lab Invest 43:262–268Google Scholar
  31. Petito CK, Schaefer JA, Plum F (1977) Ultrastructural characteristics of the brain and blood-brain barrier in experimental seizures. Brain Res 127:251–267Google Scholar
  32. Rapoport SI (1976) Blood-brain barrier in physiology and medicine. Raven Press, New YorkGoogle Scholar
  33. Turner PT (1977) Effect of pentobarbital on uptake of horseradish peroxidase by rabbit cortical synapses. Exp Neurol 54:24–52Google Scholar
  34. Westergaard E (1980) Ultrastructural permeability properties of cerebral microvasculature under normal and experimental conditions after application of tracers. Adv Neurol 28:55–74Google Scholar
  35. Westergaard E, van Deurs B, Brandsted HE (1977) Increased vesicular transfer of horseradish peroxidase across cerebral endothelium, evoked by akute hypertension. Acta Neuropathol (Berl) 37:141–152Google Scholar
  36. Westergaard E, Hertz MM, Bolwig TG (1978) Increased permeability to horseradish peroxidase across cerebral vessels, evoked by electrically induced seizures in the rat. Acta Neuropathol (Berl) 41:73–80Google Scholar

Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • C. Nitsch
    • 1
  • G. Goping
    • 1
  • H. Laursen
    • 1
  • I. Klatzo
    • 1
  1. 1.Laboratory of Neuropathology and Neuroanatomical SciencesNational Institute of Neurological and Communicative Disorders and StrokeBethesdaUSA

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