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Lead-induced abnormalities in blood-brain barrier permeability in experimental chronic toxicity

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Molecular and Chemical Neuropathology

Abstract

The aim of this paper was to determine whether prolonged drinking of lead acetate-containing water by adult rats, which imitates environmental exposure to lead (Pb), affects some morphological and biochemical properties of rat brain microvessels. We noted a significant increase of lead level in capillaries and synaptosomes obtained from brains of rats under chronic toxicity conditions. Intravenously injected horseradish peroxidase (HRP) was used to evaluate the functional state of the blood-brain barrier (BBB). The results indicate that, systematically administered at low doses, lead induces BBB dysfunction. The changes, revealed in light microscopy and confirmed by electron microscopic studies, are typical for “leaky” microvessels, reported for variety of neuropathological conditions associated with BBB damage. Enhanced pinocytotic activity of the endothelial cells and the opening of interendothelial tight junctions, together with enormous phagocytizing action of the pericytes, are the most characteristic ultrastructural features noted. The presence of specific type of perivascular cells containing droplets of lipids in the cytoplasm, together with changes in phospholipid profile in brain capillaries, suggest that altered lipid composition of membranes may, at least in part, be responsible for changes in observed membrane permeability.

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References

  • Bär T. (1987) Difference in mitochondrial content and cytochrome oxidase activity between pericytes and endothelial cells of rat brain capillaries, inStroke and Microcirculation (Cervos-Navarro, J. and Ferszt R. eds.), Raven, New York, pp. 27–33.

    Google Scholar 

  • Bligh E. G. and Dyer W. J. (1959) A rapid method of total lipid extraction and purification.Can. J. Biochem. Physiol. 37, 911–917.

    CAS  PubMed  Google Scholar 

  • Booth R. F. G. and Clark J. B. (1978) A rapid method for the preparation of relatively pure, metabolically competent synaptosomes from rat brain.Biochem. J. 176, 365–370.

    CAS  PubMed  Google Scholar 

  • Cory-Slechta D. A. and Wichowski D. V. (1991) Low level lead exposure increases sensitivity to the stimulus properties of dopamine D1 and D2 agonists.Brain Res. 553, 65–74.

    Article  CAS  PubMed  Google Scholar 

  • Davies I. M., Elias R. W., and Grant L. D. (1993) Current issues in human lead exposure and regulation of lead.NeuroToxicology 14(2–3), 15–28.

    Google Scholar 

  • Dąbrowska-Bouta B., Strużyńska L., and Rafałowska U. (1996) Does lead provoke the peroxidation porocess in rat brain synaptosomes?Mol. Chem. Neuropathol. 29, 127–139.

    PubMed  Google Scholar 

  • Deane R. and Bradbury M. W. B. (1990) Transport of lead-203 at the blood-brain barrier during short cerebrovascular perfusion with saline in the rat.J. Neurochem. 54, 905–914.

    Article  CAS  PubMed  Google Scholar 

  • Dermietzel R. and Krause D. (1991) Molecular anatomy of the blood-brain barrier as defined by immunocytochemistry, inInternational Review of Cytology. A Survey of Cell Biology, vol. 127 (Jeon K. W. and Friedlander M., eds.), Academic, San Diego, CA, pp. 57–109.

    Google Scholar 

  • Deutsch C., Drown C., Rafałowska U., and Silver I. A. (1981) Synaptosomes from rat brain: morphology, compartmentation and transmembrane pH and electrical gradients.J. Neurochem. 36, 2063–2071.

    Article  CAS  PubMed  Google Scholar 

  • Donaldson W. E. and Knowles S. O. (1993) Mini review. Is lead toxicosis a reflection of altered fatty acid composition of membranes?Comp. Biochem. Physiol. 104C,3, 377–379.

    Google Scholar 

  • Donaldson W. E. and Leeming T. K. (1984) Dietary lead: effects on hepatic fatty acid composition in chicks.Toxicol. Appl. Pharmacol. 73, 119–123.

    Article  CAS  PubMed  Google Scholar 

  • Gehrmann J., Matsumoto Y., and Kreutzberg G. W. (1995) Microglia: instrinsic immuno-effector cell of the brain.Brain Res. Rev. 20, 269–287.

    Article  CAS  PubMed  Google Scholar 

  • Goldstein G. W., Asbury A. K., and Diamond, I. (1974) Pathogenesis of lead encephalopathy: Uptake of lead and reaction of brain capillaries.Arch. Neurol. 31, 382–389.

    CAS  PubMed  Google Scholar 

  • Goyer R. A. and Rhyne B. C. (1973) Pathological effects of lead.Internat. Rev. Exp. Pathol. 12, 1–77.

    CAS  Google Scholar 

  • Grandjean P. (1993) International perspectives of lead exposure and lead toxicity.Neuro-Toxicology 14(2–3), 9–14.

    CAS  Google Scholar 

  • Grant L. D., Kimmel C. A., West G. L., Martinez-Vargos Ch. M., and Howard J. L. (1980) Chronic low-level lead toxicity in the rat.Toxicol. Appl. Pharmacol. 56, 42–58.

    Article  CAS  PubMed  Google Scholar 

  • Holtzman D., De Vries C., Ngunyen H., Olsen I., and Bensch V. (1984) Naturation of resistance to lead encephalopathy: Cellular and subcellular mechanisms.Neuro Toxicology 5, 97–124.

    CAS  Google Scholar 

  • Khalil-Manesh F., Gonick H. C., Weiler E., and Saldanha L. (1991) Effect of dimercaptosuccinic acid on lead-induced hypertension, inHeavy Metals in the Environment (Farmer J. G., ed.), International Conference, Edinburgh.

  • Kochen J. A., Greener Y., and Hirano A. (1977) Relationship of blood and brain lead levels to morphologic changes in lead-induced chick embryo encephalopathy. II. Biochemical studies, inNeurotoxicology (Roizin L., Shiraki H., and Grčević N., eds.), pp. 309–311, Raven, New York.

    Google Scholar 

  • Krigman M. R., Mushak P., and Bouldin T. W. (1977) An appraisal of rodent models of lead encephalopathy, inNeurotoxicology (Roizin L., Shiraki H., and Grčević N., eds.), pp. 299–302, Raven, New York.

    Google Scholar 

  • Lawton L. J. and Donaldson W. E. (1991) Lead-induced tissue fatty acid alterations and lipid peroxidation.Biol. Trace Elem. Res. 28, 83–97.

    Article  CAS  PubMed  Google Scholar 

  • Lowry O. H., Rosebrough N. J., Farr A. L., and Randall R. J. (1951) Protein measurements with Folin phenol reagent.J. Biol. Chem. 193, 265–275.

    CAS  PubMed  Google Scholar 

  • Mato M., Aikawa E., Mato T. K., and Kurihara K. (1986) Tridimensional observation of fluorescent granular perithelial (FGP) cells in rat cerebral blood vessels.Anat. Res. 215, 413–419.

    Article  CAS  Google Scholar 

  • McMurche E. J. and Raison J. K. (1979) Membrane lipid fluidity and its effects on the activation energy of membrane-associated enzymes.Biochim. Biophys. Acta 554, 364–374.

    Article  Google Scholar 

  • Mršulja B. B., Mršulja B. J., Fujimoto T., Klatzo I., and Spatz M. (1976). Isolation of brain capillaries: a simplified technique.Brain Res. 110, 361–365.

    Article  PubMed  Google Scholar 

  • Nag S. and Harik S. I. (1987) Cerebrovascular permeability to horseradish peroxidase in hypertensive rats: effects of unilateral locus ceruleus lesion.Acta Neuropathol. (Berl.) 73, 247–253.

    Article  CAS  Google Scholar 

  • Nagy Z., Peters H., and Huttner J. (1984) Fracture faces of cell junctions in cerebral endothelium during normal and hyperosmotic conditions.Lab. Invest. 50, 313–322.

    CAS  PubMed  Google Scholar 

  • Nakazawa T., Nishikawa M., Aikawa E., and Mato M. (1994) Localization of lipids and lipoprotein in perivascular FGP cells of rat cerebellar cortex.Acta Histochem. Cytochem. 27, 323–330.

    CAS  Google Scholar 

  • Needleman H. L. (1980)Low Level Lead Exposure. The Clinical Implications of Current Research. Raven, New York.

    Google Scholar 

  • O'Tuama L. A., Kim C. S., Gatzy J. T., Krigman M. R., and Mushak P. (1976). The distribution of inorganic lead in guinea pig brain and neural barrier tissues in control and lead-poisoned animals.Toxicol. Applied Pharmacol. 36, 1–9.

    Article  Google Scholar 

  • Pentschew A. (1965) Morphology and morphogenesis of lead encephalopathy.Acta Neuropathol. 5, 133–160.

    Article  CAS  PubMed  Google Scholar 

  • Pentschew A., and Garro F. (1966) Lead encephalomyelopathy of the suckling rat and its implications on the porphyrinopathic nervous diseases.Acta Neuropathol. 6, 266–278.

    Article  CAS  PubMed  Google Scholar 

  • Rafałowska U., Erecińska M., and Wilson D. W. (1980) Energy metabolism in rat brain synaptosomes from nembutal-anesthetized and nonanesthetized animals.J. Neurochem. 34, 1380–1386.

    Article  PubMed  Google Scholar 

  • Reese T. S., and Karnovsky M. J. (1967) Fine structural localization of a blood-brain barrier to exogenous peroxidase.J. Cell. Biol. 34, 207–215.

    Article  CAS  PubMed  Google Scholar 

  • Rouser G., Fleischer S., and Yamamoto A. (1970) Two dimensional thin layer chromatographic separation of polar lipid and determination of phospholipids by phosphorus analysis of spots.Lipids 5, 494–496.

    Article  CAS  PubMed  Google Scholar 

  • Silbergeld E. K. and Hruska E. (1980) Neurochemical investigations of low level lead exposure, inLow Level Lead Exposure. The Clinical Implication of Current Research (Needleman H. L., ed.), pp. 135–157, Raven, New York.

    Google Scholar 

  • Sternberger N. H. and Sternberger L. A. (1987) Blood-brain barrier protein recognized by monoclonal antibody.Proc. Natl. Acad. Sci. USA 74, 8169–8173.

    Article  Google Scholar 

  • Sundströ R., Müntzing K., Kalimo H., and Sourander P. (1985) Changes in the integrity of the blood-brain barrier in suckling rats with low dose lead encephalopathy.Acta Neuropathol. (Berl.) 68, 1–9.

    Article  Google Scholar 

  • Thomas J. A., Dallenbach F. D., and Thomas M. (1973) The distribution of radioactive lead (210Pb) in the cerebellum of developing rats.J. Pathol. 109, 45–50.

    Article  CAS  PubMed  Google Scholar 

  • Toews A. D., Kolber A., Hayward J., Krigman M. R., and Morell P. (1978) Experimental lead encephalopathy in the suckling rat: concentration of lead in cellular fractions enriched in brain capillaries.Brain Res. 147, 131–138.

    Article  CAS  PubMed  Google Scholar 

  • Van Deurs B. (1976) Observations on the blood-brain barrier in hypertensive rats with particular reference to phagocytic pericytes.J. Ultrastruct. Res. 56, 65–77.

    Article  PubMed  Google Scholar 

  • Walski M. and Borowicz J. (1995) Brain phagocytes and the microglia of the cerebral cortex of rats following an incident of total ischaemia.J. Brain Res. 36, 55–66.

    CAS  Google Scholar 

  • Walski M. and Chomicz L. (1996) Ultrastructural evaluation of brain phagocytes in the period of survival after clinical death.Eur. J. Haematol. 57, 21–27.

    Google Scholar 

  • Winder C., Carmichael N. G., and Lewis P. D. (1982) Effects of chronic low level lead exposure on brain development and function.Trends Neurosci. 6, 207–209.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Neurochemistry, Polish Academy of Sciences, 5 Pawińskiego St., 02-106, Warsaw, Poland

    Lidia Strużyńska, Beata Dabrowska-Bouta & Urszula Rafałowska

  2. Department of Electronic Microscopy, Polish Academy of Sciences, 5 Pawińskiego St., 02-106, Warsaw, Poland

    Michał Walski

  3. Neuropathology of Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego St., 02-106, Warsaw, Poland

    Roman Gadamski

Authors
  1. Lidia Strużyńska
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  2. Michał Walski
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  3. Roman Gadamski
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  4. Beata Dabrowska-Bouta
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  5. Urszula Rafałowska
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Correspondence to Urszula Rafałowska.

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Strużyńska, L., Walski, M., Gadamski, R. et al. Lead-induced abnormalities in blood-brain barrier permeability in experimental chronic toxicity. Molecular and Chemical Neuropathology 31, 207–224 (1997). https://doi.org/10.1007/BF02815125

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  • DOI: https://doi.org/10.1007/BF02815125

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