Newborn rats that suckled mothers eating a diet containing 4 percent lead carbonate display hyperactivity, aggressiveness, and excessive stereotyped behavior starting at 4 weeks of age. There is an eightfold increase in the concentration of lead in brain, no change in norepinephrine, but a 20 percent decrease in dopamine relative to coetaneous controls. This suggests a relationship between central nervous system dysfunction due to lead and dopamine metabolism in brain.

https://science.sciencemag.org/content/sci/182/4116/1022.full.pdf

Hyperactivity and brain catecholamines in lead-exposed developing rats.

Lead entry Into the central nervous system and effects on brain metabolism were studied in immature rats. Lead 210 readily enters the brain after intravenous injection; uptake is proportional to dose. Although blood levels fall rapidly after injection, brain lead retention is prolonged and unaffected by edetic acid therapy. In individuals who ingest lead episodically, progressive accumulation in the brain can occur without detection of changes in blood. Excessive lead deposition in the brain of nursing rat pups provokes severe hemorrhagic reactions limited to the cerebellum although lead concentrations are the same as in other brain regions. A prehemorrhagic stage of lead encephalopathy could be identified in the cerebellum by monitoring brain edema. This appears to be due to capillary dysfunction and suggests that cerebellar capillaries are more vulnerable to lead than capillaries elsewhere in the brain.

Pathogenesis of Lead Encephalopathy: Uptake of Lead and Reaction of Brain Capillaries

A lead-induced behavioral disorder

Daily oral administration of lead to newborn rats has no adverse effect on their body growth. Lead-treated rats were more active than age-matched controls. Endogenous levels of brain dopamine were unchanged, whereas norepinephrine was increased, suggesting a possible relationship between lead exposure during earliest developmental periods, increased motor activity, and brain norepinephrine, and not brain dopamine as previously postulated.

https://science.sciencemag.org/content/sci/187/4174/359.full.pdf

Growth, behavior, and brain catecholamines in lead-exposed neonatal rats: a reappraisal

Neurotoxic effects of cadmium in young rats.

Experimental lead encephalopathy was produced in developing rats. The cerebellar changes that developed were studied by light and electron microscopy. Although edema was observed in all phases of the encephalopathy, changes in the blood vessels, formation of platelet thrombi, and alterations of the Purkinje cells and their dendrites warranted special attention. The lead and calcium content of the brain and of the blood in the lead poisoned and control groups were determined chemically. The results are discussed from a morphological point of view and a hypothesis of their pathogenesis is presented.

Manaroma Thomas

Papers

Considerations on the development of experimental lead encephalopathy.