Summary
Retardation of growth has often confounded the interpretation of the results from experimental studies on lead intoxication. An attempt was therefore made to establish a daily dose of lead which, when given to suckling rags, results in a lead encephalopathy without concomitant reduction in body weight. Lead was administered i.p. as lead nitrate. Experimental animals were given 25, 10, or 5 mg lead nitrate/kg b.wt. daily during the first 20 days postnatally (p.n.). One group was given 10 mg/kg daily during the first 15 days. Controls were injected with vehicle without lead nitrate. Mortality was high in the group given 25 mg/kg b.wt. daily. Animals in this group exhibited a marked weight loss after 10 days. A slight but significant reduction in body weight was seen at 20 days in animals receiving 10 mg/kg b.wt. from day 1 to 20. The body weight gain of animals given 10 mg/kg during 15 days and of animals given 5 mg/kg during 20 days did not significantly differ from that of controls. Lead content in blood and brain was determined using a Carbon Rod Atomizer. Lead levels were elevated in all experimental animals. Light-microscopic findings in the cerebellum of animals given 25 and 10 mg/kg b.wt. daily were similar to those previously reported in experimental lead encephalopathy. The changes were dose-dependent, lesions being devastating in rats given 25 mg/kg b.wt. daily and discrete in rats given 10 mg/kg b.wt. daily. No pathologic change could be demonstrated on the light-microscopic level in the cerebellum or cerebrum of rats given 5 mg/kg b.wt. daily. The lack of growth retardation in encephalopathic rats makes the model valuable for further investigations on lead neurotoxicity.
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References
Adler MW, Adler CH (1977) Toxicity to heavy metals and relationship to seizure thresholds. Clin Pharmacol Ther 22:774–779
Akelaitis AJ (1941) Lead encephalopathy in children and adults: a clinico-pathological study. J Nerv Ment Dis 93:313–322
Alling C, Bruce Å, Karlsson I, Svennerholm L (1974) The effect of different levels of essential fatty acids on growth rate of the rat. Nutr Metab 16:38–50
Blackman SS Jr (1937) The lesions of lead encephalitis in children. Bull Johns Hopkins Hosp 61:1–61
Browder AA, Joselow MM, Louria DB (1973) The problem of lead poisoning. Medicine 52:121–135
Castellino N, Aloj S (1964) Kinetics of the distribution and excretion of lead in the rat. Br J Ind Med 21:208–214
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
Chisolm JJ Jr (1971) Lead poisoning. Sci Am 224:15–23
Choie DD, Richter GW (1972) Lead poisoning: rapid formation in intranuclear inclusions. Science 177:1194–1195
Choie DD, Richter GW (1980) Effects of lead on the kidney. In: Singhal RL, Thomas JA (eds) Lead toxicity. Urban & Schwarzenberg, München Baltimore, pp 187–212
Clasen RA, Hartman F, Starr A, Coogan PS, Pandolfi S, Laing I, Becker R, Hass G (1974a) Microscopic and chemical studies of the vascular changes and oedema of lead encephalopathy. Am J Pathol 74:215–234
Clasen RA, Hartman JF, Coogan PS, Pandolfi S, Laing I, Becker RA (1974b) Experimental acute lead encephalopathy in the juvenile Rhesus monkey. Environ Health Perspect 7:175–185
Damstra T (1977) Toxicological properties of lead. Environ Health Perspect 19:297–307
Forbes GB, Reina JC (1972) Effect of age on gastrointestinal absorption (Fe, Sr, Pb) in the rat. J Nutr 102:647–652
Gabbiani G, Baic D, Deziel C (1967) Toxicity of cadmium for the central nervous system. Exp Neurol 18:154–160
Gelman BB, Michaelson IA (1979) Neonatal lead toxicity and in vitro lipid peroxidation of the rat brain. J Toxicol Environ Health 5:671–682
Goldstein GW, Asbury AK, Diamond I (1974) Pathogenesis of lead encephalopathy. Uptake of lead and reaction of brain capillaries. Arch Neurol 31:382–389
Govoni S, Memo M, Spano PF, Trabucchi M (1979) Chronic lead treatment differentially affects dopamine synthesis in various rat brain areas. Toxicology 12:343–349
Goyer RA (1971) Lead and the kidney. Curr Top Pathol 55:147–176
Graef J (1979) Clinical aspects of lead poisoning. In: Vinken PJ, Bruyn GW (eds) Handbook of clinical neurology, vol 36. North Holland, Amsterdam Oxford, American Elsevier, New York, pp 1–34
Hirano A, Iwata M (1979) Neuropathology of lead intoxication. In: Vinken PJ, Bruyn GW (eds) Handbook of clinical neurology, vol 36. North Holland, Amsterdam Oxford, American Elsevier, New York, pp 35–64
Holtzman D, Herman MM, Shen Hsu J, Mortell P (1980) The pathogenesis of lead encephalopathy. Effects of lead carbonate feeding on morphology, lead content, and mitochondrial respiration in brains of immature and adult rats. Virschows Arch [Pathol Anat] 387:147–164
Horita N, Okuno A, Izumiyama Y (1982) Neuropathological changes obtained in perinatal and mature rats by treatment with vitamin B1-deficient diet and pyrithiamine. IXth Int Congr Neuropathol, Vienna [Abstr], p 70, B3–6
Jason KM, Kellogg CK (1980) Behavioral neurotoxicity of lead. In: Singhal RL, Thomas JA (eds) Lead toxicity. Urban & Schwarzenberg, München Baltimore, pp 241–272
Krigman MR, Hogan EL (1974) Effect of lead intoxication on the postnatal growth of the rat nervous system. Environ Health Perspect 187–199
Krigman M, Bouldin T (1975) Acute lead encephalopathy in the Guinea pig. Acta Neuropathol (Berl) 33:185–190
Krigman M (1977) An appraisal of rodent models of lead encephalopathy. In: Roizin L, Shiraki H, Grčević N (eds) Neurotoxicology, vol 1. Raven Press, New York, pp 299–302
Lin-Fu JS (1973) Vulnerability of children to lead exposure and toxicity, Part 1. New engl J Med 1229–1233, 1289–1293
Lowry OH, Rosebrough NJ, Farr AL, Randall NJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275
Luckey TD (1975) Introduction to heavy metal safety, toxicity and hormonlogy. In: Coulston F, Korte F (eds) Heavy metal safety, toxicity and hormology. Thieme, Stuttgart/Academic Press, New York San Francisco London, pp 1–3
Markov DV, Dimova RN (1974) Ultrastructural alterations of rat brain microglial cells and pericytes after chronic lead posoning. Acta Neuropathol (Berl) 28:25–35
Mahaffey KR (1980) Nutrient-lead interactions. In: Singhal RL, Thomas JA (eds) Lead toxicity. Urban & Schwarzenberg, München Baltimore, pp 425–460
Michaelson IA, Sauerhoff MW (1974) Animal models of human disease: Severe and mild lead encephalopathy in the neonatal rat. Environ Health Perspect 201–225
Michaelson IA (1980) An appraisal of rodent studies on the behavioural toxicity of lead. In: Singhal RL, Thomas JA (eds) Lead toxicity. Urban & Schwarzenberg, München Baltimore, pp 301–366
Mortensen RA, Kellogg KE (1944) The uptake of lead by blood cells as measured with a radioactive isotope. J Cell Comp Phys 23:11–20
Needleman HL (1980) Human lead exposure. In: Singhal RL, Thomas JA (eds) Lead toxicity. Urban & Schwarzenberg, München Baltimore, pp 483–504
Nriagu JO (1980) Lead in the atmosphere and its effect on lead in humans. In: Singhal RL, Thomas JA (eds) Lead toxicity. München Baltimore, pp 483–504
Okazaki H, Aronson SM, DiMaio DJ, Olvera JE (1963) Acute lead encephalopathy of childhood. Histologic and chemical studies, with particular reference to angiopathic aspects. Am Neurol Assoc 88:248–250
Oldfors A, Sourander P (1978) Barriers of peripheral nerve towards exogenous peroxidase in normal and protein-deprived rats. Acta Neuropathol (Berl) 43:129–134
Pentschew A, Garro F (1966) Lead encephalo-myelopathy of the suckling rat and its implications on the porphyrinopathic nervous diseases, with special reference to the permeability disorders of the nervous system's capillaries. Acta Neuropathol (Berl) 6:266–278
Petit TL, Alfano DP (1979) Differential experience following developmental lead exposure. Effects on brain and behaviour. Pharmacol Biochem Behav 11:165–171
Press, MF (1977) Lead encephalopathy in neonatal Long-Evans rats: Morphologic studies. J Neuropathol Exp Neurol 36:169–195
Richardsson KC, Jarret L, Finke EH (1960) Embedding in epoxyresins for ultrathin sectioning in electron microscopy. Stain Technol 35:313–323
Rosenblum WI, Johnson MG (1968) Neuropathologic changes produced in suckling mice by adding lead to the maternal diet
Saito K (1973) Electroencephalographic studies on petrol intoxication: comparison between nonleaded and lead white petrol. Br J Ind Med 30:352–358
Silbergeld EK, Goldberg A (1980) Problems in experimental studies of lead poisoning. In: Singhal RL, Thomas JA (eds) Lead toxicity. Urban & Schwarzenberg, München Baltimore, pp 19–42
Sobotka TJ, Brodie RE, Cook MP (1975) Psychophysiological effects of early lead exposure. Toxicology 5:175–191
Stone HM (1981) Chemical of the month, Lead. J Chem Educ 58:722–724
Suzuki T, Yoshida A (1979) Effect of dietary supplementation of iron and ascorbic acid on lead toxicity in rats. J Nutr 109:982–988
Thomas JA, Dallenbach FD, Thomas M (1973) The distribution of radioactive lead (210Pb) in the cerebellum of developing rats. J Pathol 109:45–50
Toews AD, Kolber A, Hayward 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
Toews AD, Krigman MR, Thomas DJ, Morell P (1980) Effect of inorganic lead exposure on myelination in the rat. Neurochem Res 5:605–616
Tuthill R (1929) Neuropathologic changes in a case of lead encephalopathy. Buffalo Gen Hosp Bull 7:15–19
Webster WS, Valois AA (1981) The toxic effects of cadmium on the neonatal mouse CNS. J Neuropathol Exp Neurol 40:247–257
WHO (1977) Environmental health criteria. Lead. WHO, Geneva
Willes RF, Rice DC, Truelove JF (1980) Chronic effects of lead in nonhuman primates. In: Singhal RL, Thomas JA (eds) Lead toxicity. Urban & Schwarzenberg, München Baltimore, pp 213–240
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Supported by grants from the Swedish Medical Research Council, project nos. 03488 (to P. Sourander) and 6345 (to N. G. Conradi) and from the Medical Faculty, University of Göteborg, Sweden
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Sundström, R., Conradi, N.G. & Sourander, P. Low-dose lead encephalopathy in the suckling rat. Acta Neuropathol 60, 1–8 (1983). https://doi.org/10.1007/BF00685340
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DOI: https://doi.org/10.1007/BF00685340