Neurotoxic effects of metals on blood brain barrier impairment and possible therapeutic approaches.

Abstract

Exposure to neurotoxic and heavy metals (Pb²⁺, As³⁺, Mn²⁺, Cd²⁺, etc) has increased over time and has shown to negatively affect brain health. Heavy metals can cross the blood brain barrier (BBB) in various ways including receptor or carrier-mediated transport, passive diffusion, or transport via gaps in the endothelial cells of the brain. In high concentrations, these metals have been shown to cause structural and functional impairment to the BBB, by inducing oxidative stress, ion dyshomeostasis, tight junction (TJ) loss, astrocyte/pericyte damage and interference of gap junctions. The structural and functional impairment of the BBB results in increased BBB permeability, which ultimately leads to accumulation of these heavy metals in the brain and their subsequent toxicity. As a result of these effects, heavy metals are correlated with various neurological disorders. The pathological effects of these heavy metals can be effectively mitigated via chelation. In addition, it is possible to treat the associated disorders by counteracting the molecular mechanisms associated with the brain and BBB impairment.