Neurotoxicity, of lead

With disruption of this barrier, molecules such as albumin freely enter the brain and ions and water follow. Because the brain lacks a well-developed lymphatic system, clearance of plasma constituents is slow, edema occurs, and intracranial pressure rises. At lower levels of exposure, subtle dysfunction of the blood-brain barrier may contribute to neurobehavioral deficits in children (Bressler and Goldstein 1991 Goldstein 1993). The particular vulnerability of the fetus and infant to the neurotoxicity of lead may be due in part to immaturity of the blood-brain barrier and to the lack of the high-affinity leadbinding protein in astroglia, which is discussed later in this section. Results of measurements of transendothelial electrical resistance across the blood-brain barrier from mice of various ages showed that lead potentiates cytokines-induced increase in ion permeability of the blood-brain barrier (Dyatlov et al. 

One of the most sensitive systems affected by lead exposure is the nervous system. Encephalopathy is characterized by symptoms such as coma, seizures, ataxia, apathy, bizarre behavior, and incoordination (CDC 1985). Children are more sensitive to neurological changes. In children, encephalopathy has been associated with PbB levels as low as 70 pg/dL (CDC 1985). The most sensitive peripheral index of neurotoxicity of lead is reported to be slowed conduction in small motor libers of the ulnar nerve in workers with 30-40 pg/dL lead in blood (Landrigan 1989). Other potential biomarkers of lead suggested for neurotoxicity in workers are neurological and behavioral tests, as well as cognitive and visual sensory function tests (Williamson and Teo 1986). However, these tests are not specific to elevated lead exposure... 

Davis JM, Otto DA, Weil DE, et al. 1990. The comparative development neurotoxicity of lead in humans and animals. Neurotoxicol Teratol 12 215-229. 

Davis MJ. 1990. Risk assessment of the developmental neurotoxicity of lead. Neurotoxicology 11 285-292. 

Once absorbed, foreign compounds may react with plasma proteins and distribute into various body compartments. In both neonates and elderly human subjects, both total plasma-protein and plasma-albumin levels are decreased. In the neonate, the plasma proteins may also show certain differences, which decrease the binding of foreign compounds, as will the reduced level of protein. For example, the drug lidocaine is only 20% bound to plasma proteins in the newborn compared with 70% in adult humans. The reduced plasma pH seen in neonates will also affect protein binding of some compounds as well as the distribution and excretion. Distribution of compounds into particular compartments may vary with age, resulting in differences in toxicity. For example, morphine is between 3 and 10 times more toxic to newborn rats than adults because of increased permeability of the brain in the newborn. Similarly, this difference in the blood-brain barrier underlies the increased neurotoxicity of lead in newborn rats. 

Rajanna, B Alcorn State University Lorman, MS Developmental neurotoxicity of lead and methyl nercury. NIGMS... 

In all, the reported neurochemical effects tend to confuse, rather than aid comprehension of the neurotoxicity of lead. Some effects appear to be seen in the catecholaminergic systems at relatively low doses of lead. As lead-induced changes in other major neurotransmitter systems are generally seen at moderate to high exposures, the question of what is a relevant or justifiable level of lead must again be asked. 

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