The morphological effects of lead on the developing central nervous system.

The pathological changes found in the central nervous system of lead-exposed humans and laboratory animals are reviewed. Data in man relate to relatively high exposure levels. In human childhood lead encephalopathy, which occurs with blood lead levels in the range 100-800 micrograms Pb/100 ml, oedema, vacuolation, haemorrhage and reactive glial changes appear to be secondary to microvascular lesions. No primary neuronal lesions have yet been clearly identified. Neurological signs and a pathological picture closely resembling that seen in human lead encephalopathy are obtained in young lead-exposed rats with blood lead levels above 500 micrograms Pb/100 ml. Oedema and haemorrhage, cyst formation, reactive glial changes and nerve cell alterations are observed consequent to changes in capillary endothelial cells and basement membranes. High-level lead exposure in rats also produces disturbances in myelinated axons and may affect neural network formation in the central nervous system. With intermediate lead levels (200-500 microgram Pb/100 ml blood), vascular changes and their sequelae are not seen, but nutritional effects occur which may produce neuropathological changes. Data from recent studies on developing rats with low blood levels (up to 100 microgram Pb/100 ml) appear to show effects of lead on maturing and differentiated nerve cell populations. The relevance of these changes to human subclinical lead intoxication remains to be seen. However, the overall correspondence of findings in lead-poisoned man and rat would make further investigation in this area appear necessary.