Although lead poisoning is an important public health problem, the pathogenesis of the neurotoxicity is not well understood. We propose to study the metabolic basis of the acute encephalopathy which is produced in young rats pups by feeding their mother lead carbonate. The young rats develop severe cerebellar edema which has the same pathological features found in human cases of lead poisoning. There is histological and chemical evidence that the primary distrubances in acute lead encephalopathy may be an increased permeability of brain capillaries to plasma. We have adapted a procedure for the isolation of capillaries from brain for use in rats. We have shown that the isolated capillaries retain enzymatic and metabolic activity and now plan to define the metabolic reaction occurring in the capillaries of rats with lead encephalopathy. In addition to preparation of the animal model and the isolated brain capillaries, methods will include measurement of the permeability of the capillary preparation to protein and lead, monitoring of cellular integrity as indicated by glucose uptake, glucose metabolism and oxygen consumption, and assay of those enzymes which may serve as biochemical markers for the different cellular and subcellular fractions of brain and of those known to be inhibited by low concentrations of lead.
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