Delivery of Metals to Brain and the Role of the Blood-Brain Barrier

Metals serve critical roles in brain as essential cofactors, catalysts, second messengers, and modulators of gene, enzyme, and receptor activity. Currently, eight metals, including calcium, magnesium, iron, copper, zinc, manganese, cobalt, and molybdenum, are known to be required for the normal development and function of the brian (Prohaska, 1987). Each must be supplied at specific levels to avoid signs of deficiency or toxic excess. Others, such as lead, aluminum, and mercury, are not essential, but are toxic if allowed to accumulate in the nervous system. Several metals, including iron, stimulate free radical formation and have been linked to oxidative damage in neurological disorders, including ischemia, stroke, and Parkinson’s disease (Riederer et al., 1989; Dexter et al., 1989; Griffiths and Crossman, 1993).