Toxic effects of lead in the developing nervous system: in oculo experimental models

Modern man is chronically exposed to lead in the biosphere at levels several orders of magnitude higher than the natural level that once existed. There is much concern about the possible adverse effects of this population-wide, low-level lead exposure, particularly on the developing organism, wherein the central nervous system may be one primary target. We have developed in oculo test systems, which permit temporal and spatial discrimination of possible effects of lead and other potential neurotoxic agents in the environment on the developing central nervous system as well as on different types of peripheral nerves in the adult. In one experimental protocol, defined areas of the fetal rat brain are grafted to the anterior chamber of the eye of adult rat recipients that are exposed to lead. Such grafts will become vascularized from the host iris and continue developing in oculo. Thus, grafted brain tissue and host brain will share circulation and therefore be exposed to similar amounts of lead. Studies of cerebellar grafts revealed that, although there was a normal gross cytological development in the presence of lead, there was a marked and permanent impairment of spontaneous discharge rates of the grafted Purkinje neurons as observed with electrophysiological techniques long after cessation of lead treatment. The host Purkinje neurons were not affected. A similar, although less dramatic, impairment of cerebellar function could be subsequently demonstrated in intact animals when newborn rats were given lead during the first 20 days of life and studied as adults.(ABSTRACT TRUNCATED AT 250 WORDS)