THE HISTORY OF IRON IN THE BRAIN

Brain iron research began in the late nineteenth century when Zaleski (1886) made a quantitative analysis of one human brain and correlated iron levels with observations on stained slices and some microscopic s ections. Gradually, the realization grew that the central nervous syst em (CNS) contained iron which was different from hemoglobin-iron. This non-heme iron was found in highest concentrations in globus pallidus, substantia nigra, red nucleus, and dentate nucleus. The enhancement o f the traditional histochemical stain, potassium ferrocyanide in hydro chloric acid, by incubating the reacted sections in a solution of diam inobenzidine and hydrogen peroxide, revealed iron in many cell types o f the CNS, including neurons, microglia, oligodendroglia, and some ast rocytes. A large proportion of the soluble brain iron was shown to be present in ferritin. Brain ferritin was found to be very similar to th e protein from other organs in that it contained heavy and light subun its. Several investigators reported the presence of other iron-related proteins in the central nervous system, including transferrin, transf errin receptor, and the ferritin repressor protein. Brain was shown to respond to the extravasation of blood by converting the iron in heme to hemosiderin by a sequence of steps which was quite similar to the p rocess in extracerebral organs. The methods of molecular biology have contributed greatly to our understanding of brain iron but many questi ons remain about its unique anatomical distribution and its role in de generative diseases such as Parkinson's disease and Alzheimer's dement ia.