title: Low-level lead-induced neurotoxicity in children: an update on central nervous system effects.
abstract: The neurotoxicity of low-level long-term exposure to lead has a special relevance in children. An extensive database has provided a direct link between low-level lead exposure and deficits in the neurobehavioral-cognitive performance evidenced in childhood through adolescence. Electrophysiological studies showed that neurosensory processing may be affected by lead, with consequent decrease in auditory sensitivity and visuomotor performance. Lead disrupts the main structural components of the blood-brain barrier by primary injury to astrocytes with a secondary damage to the endothelial microvasculature. Within the brain, lead-induced damage occurs preferentially in the prefrontal cerebral cortex, hippocampus and cerebellum. Some characteristic clinical features of lead poisoning may be attributed to this specific anatomical pattern. The cellular, intracellular and molecular mechanisms of lead neurotoxicity are numerous, as lead impacts many biological activities at different levels of control: at the voltage-gated channels and on the first, second and third messenger systems. These effects could be related to lead's ability to interfere with the regulatory action of calcium in cell functions. Consequently, it may be assumed that lead acts as a chemical stressor and causes breakdown of the homeostatic cellular mechanisms. This is expressed in both the anatomical site and the neurotransmitter systems which are crucial in modulating emotional response, memory and learning. There is no threshold below which lead remains without effect on the central nervous system; thus, symptoms could simply be a clinical reflection of the brain regions preferentially involved. In integrating these physiological and clinical data, it may be suggested that the different mechanisms of low level lead neurotoxicity have a final common functional pathway.
authors.affiliation: Department of Neurology, Shaare Zedek Medical Center, P.O. Box 3235, Jerusalem 91031, Israel. yfinkel@md2.huji.ac.il
authors.forename: Y
authors.initials: Y
authors.lastname: Finkelstein
authors.forename: M E
authors.initials: ME
authors.lastname: Markowitz
authors.forename: J F
authors.initials: JF
authors.lastname: Rosen
mesh_terms: D000818:Animals; D001822:Body Burden; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D002648:Child; D003071:Cognition / Q000187:drug effects*; D006801:Humans; D007854:Lead / Q000633:toxicity*; D007855:Lead Poisoning / Q000503:physiopathology*; D008959:Models, Neurological; D009498:Neurotoxins; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D009498:Neurotoxins; D007854:Lead