Metabolism and neurotoxicity of hemin and hemin-derived iron

Funded Activity Summary

Stroke is a leading cause of death and disability in industrialised countries. Much of the brain damage that follows a hemorrhagic stroke is attributable to the presence of free iron which mediates oxidative stress in brain cells. This iron originates from hemin, which in turn is derived from the hemoglobin in extravasated blood cells. The fact that iron is freed from hemin in the post-stroke period makes it an attractive therapeutic target. However, remarkably little is known about the metabolism of hemin by the different types of brain cells. The present project investigates the metabolism and neurotoxicity of hemin in brain cells and will examine the capacity of potential therapeutic agents to protect brain cells from hemin toxicity. The data obtained from this project will advance our understanding of the uptake and metabolism of hemin by the four main types of brain cell, and the factors that are likely to be involved in the neurotoxicity of hemin-derived iron following hemorrhagic stroke. The study will also provide data concerning the relative effectiveness of potential therapeutic agents, and information concerning the cell types, time points and aspects of hemin metabolism that are most effectively targeted by these agents. Such advances will guide the development of therapeutic approaches that are directed at minimising the brain damage which results from hemin-derived iron in humans.

Funded Activity Details

Start Date: 01-01-2005

End Date: 01-01-2007

Funding Scheme: NHMRC Project Grants

Funding Amount: $346,400.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Cellular Nervous System

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

Brain cell cultures | Cell death | Heme | Hemorrhagic stroke | Metal toxins | Neuroglia | Neurotoxicity | Oxidative stress | Rat cerebral cortex

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