Experimental superficial siderosis of the central nervous system: biochemical correlates
Autor: | Rosemary C. Borke, Richard C. Chu, Arnulf H. Koeppen, Andrew C. Dickson, Craig G. Hurwitz, Richard E. Dearborn |
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Rok vydání: | 1992 |
Předmět: |
Pathology
medicine.medical_specialty Siderosis Iron Central nervous system Immunocytochemistry Enzyme-Linked Immunosorbent Assay Hemosiderin Biology Cytosol Central Nervous System Diseases Cerebellum medicine Animals Iron Regulatory Protein 1 Brain Chemistry Cerebral Cortex Microglia Histocytochemistry Iron-Regulatory Proteins RNA-Binding Proteins medicine.disease Superficial siderosis Ferritin Kinetics medicine.anatomical_structure Neurology Ferritins biology.protein Electrophoresis Polyacrylamide Gel Neurology (clinical) Hemoglobin Rabbits |
Zdroj: | Journal of the neurological sciences. 112(1-2) |
ISSN: | 0022-510X |
Popis: | The pathogenesis of superficial siderosis of the central nervous system (CNS) may be examined by the repeated intracisternal injection of washed autologous red blood cells (RBC). In rabbits, the injections cause the accumulation of iron in the cytoplasm of microglial cells and astrocytes of cerebellar and cerebral cortices. Immunocytochemistry for ferritin reveals enhanced reaction product mainly in microglia but hemosiderin occurs only after extending the injections to 6 months. In an effort to determine the biochemical correlates of these morphological changes, iron, ferritin, ferritin subunits and the ferritin repressor protein (FRP) were quantitated. There was no increase of total iron or ferritin in the exposed cortical areas. However, the injections of RBC caused dramatic shifts of the relative contributions by heavy (H-) and light (L-) ferritin subunits. The initial response was a prompt increase of the H/L ratio to over 4.0 from the normal ratio near 1.0. Extended injections caused the ratio to drop to below unity, and the predominance of L-ferritin at 6 months coincided with the appearance of granular hemosiderin. This investigation also confirmed the presence of FRP in rabbit brain cytosols but the induction of experimental superficial siderosis did not change its levels or in vitro affinity for the iron-responsive element in ferritin messenger ribonucleic acid. It is proposed that the incrustation by hemosiderin which characterizes superficial siderosis of the CNS in humans occurs when prolonged exposure to hemoglobin produces persistent shifts of the H/L-ratios by accumulation of L-ferritin. |
Databáze: | OpenAIRE |
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