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Changes in the integrity of the blood-brain barrier in suckling rats with low dose lead encephalopathy

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Previous studies on the toxic effects of lead on the brains of young animals have shown damage to the blood-brain barrier (BBB) which in severe forms appears as hemorrhagic encephalopathy. In those studies the doses of lead have been of such magnitude that lead-induced anorexia resulting in growth retardation has contributed to the extent of the injury (Sundström et al. 1984). The growth retardation can be prevented by using low lead doses (Sundström et al. 1983). Consequently, we have examined to which extent the BBB is injured in suckling rats with low dose lead encephalopathy. This was done by a) testing the permeability of the BBB to plasma proteins and b) assessing the possible occurrence of vasogenic edema by measuring the specific gravity of brain tissue. Low dose lead encephalopathy was induced by daily i.p. injections of lead nitrate 10 mg/kg body weight (b.wt.) for the first 15 days. The lead contents of the blood and homogenates of the cerebrum and cerebellum were assayed by atomic absorption spectrophotometry.

The brains were examined at 15, 20, or 30 days of age. When Evans blue-albumin (EBA) was injected i.v. 2 h before killing, most 15-day-old rats exposed to lead displayed a bluish discoloration in their cerebellum. Microscopically, red fluorescence of EBA was seen in the blue-stained regions. Immunohistochemically, extravasation of albumin, fibrinogen, and fibronectin was demonstrated as positive staining in the cerebellar cortex, with diffuse spread to the white matter of the corresponding folium. Neither lead-exposed rats aged 20 or 30 days nor any non-exposed rats revealed macroscopic or microscopic leakage of plasma proteins in the brain parenchyma. The specific gravity of the cerebral and cerebellar cortices and the hippocampus of control and lead-exposed rats aged 15 and 20 days was determined using density gradients of Percoll. No increment in the water content was encountered. Rather, the specific gravity of cerebellum of lead-treated rats aged 15 days was slightly higher than that of the controls, though statistical significance for this difference was reached only when nonparametric tests were applied. Our results indicate that low dose lead encephalopathy results in a breakdown of the BBB to plasma proteins without marked vasogenic brain edema. The hypothesis is advanced that the leakage of plasma results in rapid normalization of the tissue water content, whereas proteins remain longer in the parenchyma.

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  1. Blackman SS, Jr (1937) The lesions of lead encephalitis in children. Bull Johns Hopkins Hosp 61:1–61

  2. Carmichael NG, Winder C, Lewis PD (1981) Dose response relationships during perinatal lead administration in the rat: A model for the study of lead effects on brain development. Toxicology 21:117–128

  3. Cavanagh JB (1979) The neuropathology of lead poisoning. In: Cavanagh JB, Thomas Smith W (eds) Recent advances in neuropathology. Churchill Livingstone, Edinburgh London New York, pp 255–265

  4. Chisolm (1971) Lead poisoning. Sci Am 224:15–23

  5. Chui E, Wilmes F, Sotelo JE, Horie R, Fujiwara K, Suzuki R, Klatzo I (1981) Immunocytochemical studies on extravasation of serum proteins in cerebrovascular disorders. In: Cervos-Navarro J, Fritschka E (eds) Cerebral microcirculation and metabolism. Raven Press, New York, pp 121–127

  6. Clasen RA, Hartman JF, Coogan PS, Pandolfi S, Laing I, Becker RA (1974a) Experimental acute lead encephalopathy in the juvenile rhesus monkey. Environ Health Perspect 7:175–185

  7. Clasen RA, Hartman JF, Coogan PS, Pandolfi S, Laing I, Becker RA, Hass G (1974b) Microscopic and chemical studies of the vascular changes and edema of lead encephalopathy. Am J Pathol 74:215–234

  8. Gazendam J, Gwan-Go K, van Zanten AK (1979) Composition of isolated edema fluid in cold-induced brain edema. J Neurosurg 51:70–77

  9. Holtzmann D, Herman MM, Shen Hsu J, Mortell P (1980) The pathogenesis of lead encephalopathy. Effects of lead carbonate feedings on morphology, lead content, and mitochondrial respiration in brains of immature and adult rats. Virchows Arch [Pathol Anat] 387:147–164

  10. Holtzmann D, de Vries C, Hung Nguyen BA, Jameson N, Olson J, Carrithers M, Bensch K (1982) Development of resistance to lead encephalopathy during maturation in the rat pup. J Neuropathol Exp Neurol 41:652–663

  11. Hossmann KA, Blöink M, Wilmes F, Wechsel W (1980) Experimental peritumoral edema of the cat brain. In: Cervos-Navarro J, Ferszt R (eds) Advances in neurology, vol 28. Raven Press, New York, pp 323–340

  12. Klatzo I (1967) Presidential address. Neuropathological aspects of brain edema. J Neuropathol Exp Neurol 26:1–14

  13. Klatzo I, Chui E, Fujiwara K, Spatz M (1980) Resolution of vasogenic brain edema. In: Cervos-Navarro J, Ferszt R (eds) Advances in neurology vol 28. Raven Press, New York, pp 350–373

  14. Krigman M (1977) An apraisal of rodent models of lead encephalopathy. In: Roizin L, Shiraki H, Grecevic N (eds) Neurotoxicology, vol 1. Raven Press, New York, pp 299–302

  15. Lampert P, Garro F, Pentschew A (1967) Lead encephalopathy in suckling rats. An electron-microscopic study. In: Klatzo I, Seitelberger F (eds) Brain edema. Springer, Berlin Heidelberg New York, pp 207–222

  16. Lefauconnier JM, Hauw JJ, Bernard G (1983) Regressive or lethal lead encephalopathy in the suckling rat. J Neuropathol Exp Neurol 42:177–190

  17. Morgane PJ, Miller M, Kemper T, Stern W, Forbes W, Hall R, Bionzino J, Kissane J, Hawrylewicz E, Resnick O (1978) The effects of protein malnutrition on the developing central nervous system in the rat. Neurosci Behav Rev 137–230

  18. McClain RM, Becker BA (1975) Teratogenicity, fetal toxicity and placental transfer of lead nitrate in rats. Toxicol Appl Pharmacol 31:72–82

  19. Michaelsson IA, Sauerhoff MW (1974) Animal models of human disease: Severe and mild lead encephalopathy in the neonatal rat. Environ Health Perspect 201–225

  20. Needleman HL (1980) Human lead exposure. In: Singhal RL, Thomas JA (eds) Lead toxicity. Urban & Schwarzenberg. München Baltimore, pp 483–504

  21. Peristein MA, Attala R (1966) Neurologic sequelae of plumbism in children. Clin Pediatr 6:292–298

  22. Pertoft H, Laurent TC (1977) Isopycnic separation of cells and cell organelles by centrifugation in modified colloidal silica gradients. In: Catsimpoolas N (ed) Methods of cell separation, vol 1. Plenum Press, New York, pp 25–65

  23. Pertoft H, Laurent TC, Låås T (1978) Density gradients prepared from colloidal silica particles coated by polyvinyl-pyrrolidone (Percoll). Ann Biochem 88:271–282

  24. Powell HC, Myers RR, Lampert PW (1980) Edema in neurotoxic injury. In: Spencer PS, Schaumburg H (eds) Experimental and clinical neurotoxicology. Williams and Wilkins, Baltimore, pp 118–138

  25. Press MF (1977) Lead encephalopathy in neonatal Long-Evans rats: Morphologic studies. J Neuropathol Exp Neurol 36:169–195

  26. Steinwall O, Klatzo I (1966) Selective vulnerability of the blood-brain barrier in chemically induced lesions. J Neuropathol Exp Neurol 25:542–559

  27. Sundström R, Conradi NG, Sourander P (1983) Low dose lead encephalopathy in the suckling rat. Acta Neuropathol (Berl) 60:1–8

  28. Sundström R, Conradi NG, Sourander P (1984) Vulnerability to lead in protein deprived suckling rats. Acta Neuropathol (Berl) 62:276–283

  29. Tengvar C, Forssén M, Hultström D, Olsson Y, Pertoft H, Pettersson Å (1982) Measurement of edema in the nervous system. Use of Percoll density gradients for determination of specific gravity in cerebral cortex and white matter under normal conditions and in experimental cytotoxic brain edema. Acta Neuropathol (Berl) 57:143–150

  30. Thomas JA, Dallenbach FD, Thomas M (1973) The distribution of radioactive lead (210Pb) in the cerebellum of developing rats. J Pathol 109:45–50

  31. Toews AD, Kolber A, Hayward J, Krigman MR, 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

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Correspondence to R. Sundström.

Additional information

Financed by grants from the Swedish Medical Research Council (project nos. 03488 and 07123), from the Medical Faculty, University of Göteborg, and from the Göteborg Royal Society for Sciences and Arts

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Sundström, R., Müntzing, K., Kalimo, H. et al. Changes in the integrity of the blood-brain barrier in suckling rats with low dose lead encephalopathy. Acta Neuropathol 68, 1–9 (1985). https://doi.org/10.1007/BF00688948

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Key words

  • Lead
  • Rat
  • Brain
  • Blood-brain barrier
  • Specific gravity