Neurotoxicology of the Brain Barrier System: New Implications

Abstract

The concept of a barrier system in the brain has existed for nearly a century. The barrier that separates the blood from the cerebral interstitial fluid is defined as the blood-brain barrier, while the one that discontinues the circulation between the blood and cerebrospinal fluid is named the blood-cerebrospinal fluid barrier. Evidence in the past decades suggests that brain barriers are subject to toxic insults from neurotoxic chemicals circulating in blood. The aging process and some disease states render barriers more vulnerable to insults arising inside and outside the barriers. The implication of brain barriers in certain neurodegenerative diseases is compelling, although the contribution of chemical-induced barrier dysfunction in the etiology of any of these disorders remains poorly understood. This review examines what is currently understood about brain barrier systems in central nervous system disorders by focusing on chemical-induced neurotoxicities including those associated with nitrobenzenes, N-methyl-D-aspartate, cyclosporin A, pyridostigmine bromide, aluminum, lead, manganese, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and 3-nitropropionic acid. Contemporary research questions arising from this growing understanding show enormous promises for brain researchers, toxicologists, and clinicians.

Occupational Exposure to Welding Fume among Welders: Alterations of Manganese, Iron, Zinc, Copper, and Lead in Body Fluids and the Oxidative Stress Status

“…10,16,20,45 A predominant intracellular overload of iron and subsequent iron-mediated oxidative stress may lead to damage of neurons. Results in this study showed that exposure to the welding fume significantly increased the concentration of iron in serum.…”

“…In the current human study, the career welders did show a significantly higher Although the precise mechanism by which manganese induces neurodegenerative toxicity is poorly understood, evidence suggests that manganese toxicity may be partly the result of its action on iron homeostasis. 10,16,20,45 A predominant intracellular overload of iron and subsequent iron-mediated oxidative stress may lead to damage of neurons. Results in this study showed that exposure to the welding fume significantly increased the concentration of iron in serum.…”

“…13,15,18 Particularly regarding manganese-induced neurotoxicity, studies have shown that chronic exposure to manganese appears to be associated with altered iron concentrations in blood as well as in the cerebrospinal fluid, presumably the result of Mn-Fe interaction at certain [Fe-S]-containing proteins, which regulate the homeostasis of iron. 10,16,[19][20][21] The excess accumulation of iron in neurons may consequently produce cellular oxidative stress, leading to neuronal damage.…”

“…13,15,18 Particularly regarding manganese-induced neurotoxicity, studies have shown that chronic exposure to manganese appears to be associated with altered iron concentrations in blood as well as in the cerebrospinal fluid, presumably the result of Mn-Fe interaction at certain [Fe-S]-containing proteins, which regulate the homeostasis of iron. 10,16,[19][20][21] The excess accumulation of iron in neurons may consequently produce cellular oxidative stress, leading to neuronal damage.Superoxide dismutase (SOD), a cytoplasmic enzyme, catalyzes the reaction to decompose superoxide free radicals generated due to the cellular oxidative stress and thus has been described as a specific superoxide radical scavenger. 22 The activity of SOD in erythrocytes is directly associated with the oxidative status and has been used as the marker for systemic oxidative stress.…”

Macromolecules involved in production and metabolism of beta-amyl oid at the brain barriers

“…Brain barriers contribute to the etiology of AD mainly in three aspects: (i) the aging of cerebral vascular structure in the overall aging process of the brain, (ii) as the site of transport of extracerebral Aβ into the brain, and (iii) the ability to prevent Aβ aggregation by removing it (Zheng, 2001). The blood-brain barrier (BBB) separates blood from the interstitial fluid surrounding the neurons and neuroglia, and the blood-CSF barrier (BCB) separates the blood and CSF in and around the brain.…”