Heme and Iron Metabolism: Role in Cerebral Hemorrhage

Abstract

Heme and iron metabolism are of considerable interest and importance in normal brain function as well as in neurodegeneration and neuropathologically following traumatic injury and hemorrhagic stroke. After a cerebral hemorrhage, large numbers of hemoglobin-containing red blood cells are released into the brain's parenchyma and/or subarachnoid space. After hemolysis and the subsequent release of heme from hemoglobin, several pathways are employed to transport and metabolize this heme and its iron moiety to protect the brain from potential oxidative stress. Required for these processes are various extracellular and intracellular transporters and storage proteins, the heme oxygenase isozymes and metabolic proteins with differing localizations in the various brain-cell types. In the past several years, additional new genes and proteins have been discovered that are involved in the transport and metabolism of heme and iron in brain and other tissues. These discoveries may provide new insights into neurodegenerative diseases like Alzheimer's, Parkinson's, and Friedrich's ataxia that are associated with accumulation of iron in specific brain regions or in specific organelles. The present review will examine the uptake and metabolism of heme and iron in the brain and will relate these processes to blood removal and to the potential mechanisms underlying brain injury following cerebral hemorrhage.

Role of Red Blood Cell Lysis and Iron in Hydrocephalus after Intraventricular Hemorrhage

“…10 It is well known that brain iron overload can stimulate free radical production and cause oxidative injury, including lipid peroxidation and DNA damage. 18,24,25 The current study shows that injection of lysed RBCs, but not packed RBCs, can mimic the acute ventricular enlargement induced by IVH. …”

Heme: a versatile signaling molecule controlling the activities of diverse regulators ranging from transcription factors to MAP kinases

“…Hemopexin, albumin, a-1-microglobulin, and reduced glutathione are the most well-known heme-binding molecules [15,141]. Hemopexin is an intravascular protein that binds free heme with a very high affinity and protects against heme toxicity in vitro [141][142][143].…”

BilirubinOxidation Products (BOXes) and Their Role in Cerebral Vasospasm after Subarachnoid Hemorrhage

“…Heme oxygenase-2 is constitutively expressed in many cells including neurons and vascular endothelial cells (Govindaraju et al, 2005;Maines, 2000). Heme oxygenase-1 is the inducible heat-shock protein that is induced by heme, iron, heat shock, free radicals, and other stimuli in a variety of cells, including macrophages, brain microglia, and vascular smooth muscle cells (Foresti et al, 1999;Govindaraju et al, 2005;Maines, 2000;Sharp et al, 1999;Wagner et al, 2003). Injection of blood (Matz et al, 1996a, b, c), or injections of pure Hb into the subarachnoid space induces HO-1 in microglia throughout the brain (Turner et al, 1998).…”