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Hemorrhagic stroke is a common cause of permanent brain damage, with a significant amount of the damage occurring in the weeks following a stroke. This secondary damage is partly due to the toxic effects of hemin, a breakdown product of hemoglobin. The serum proteins hemopexin and albumin can bind hemin, but these natural defenses are insufficient to cope(More)
Iron is essential for the normal functioning of cells but since it is also capable of generating toxic reactive oxygen species, the metabolism of iron is tightly regulated. The present article advances the view that astrocytes are largely responsible for distributing iron in the brain. Capillary endothelial cells are separated from the neuropil by the(More)
Astrocytes are considered to play an important role in iron homeostasis of the brain, yet the mechanisms involved in the uptake of iron into astrocytes remain elusive. To investigate the uptake of iron into astrocytes, we have applied ferric ammonium citrate (FAC) to rat astrocyte-rich primary cultures. These cultures express the mRNAs of two membrane-bound(More)
Hemin is a breakdown product of the blood protein, hemoglobin and is responsible for much of the secondary damage caused following a hemorrhagic stroke. Hemin is toxic to cultured astrocytes and it is thought that this toxicity is due to iron that is liberated when hemin is degraded. However, free iron applied to astrocytes is not toxic and the reason for(More)
Brains from patients with Alzheimer disease (AD) show a disruption in the metabolism of iron, such that there is an accumulation of iron in senile plaques, and an altered distribution of iron transport and storage proteins. One of the earliest events in AD is the generation of oxidative stress, which may be related to the generation of free radicals by the(More)
Iron that is not bound to storage proteins can catalyse the generation of toxic hydroxyl radicals. Iron can be released from brain storage proteins by hypoxic conditions, such as those that accompany stroke, and the situation can be compounded by iron released from hemoglobin in extravasated blood cells. Despite the neurotoxicity of iron, there is little(More)
In epilepsy, traumatic brain injury, and ischemic stroke, toxic levels of zinc released from neurons contribute to the brain damage associated with these disorders. Zinc causes oxidative stress by increasing the generation of reactive oxygen species and by inhibiting glutathione reductase (GR). This study investigated whether naturally occurring amino acids(More)
Hemin is cytotoxic, and contributes to the brain damage that accompanies hemorrhagic stroke. In order to better understand the basis of hemin toxicity in astrocytes, the present study quantified hemin metabolism and compared it to the pattern of cell death. Heme oxygenase-1 (HO-1) expression was first evident after 2 h incubation with hemin, with maximal(More)
Neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease, and hemorrhagic stroke are associated with increased levels of non-transferrin-bound iron (NTBI) in the brain, which can promote Fenton chemistry. While all types of brain cells can take up NTBI, their efficiency of accumulation and capacity to withstand iron-mediated toxicity(More)
The release of zinc (Zn) from glutamatergic synapses contributes to the neuropathology of ischemia, traumatic brain injury, and stroke. Astrocytes surround glutamatergic synapses and are vulnerable to the toxicity of Zn, which impairs their antioxidative glutathione (GSH) system and elevates the production of reactive oxygen species (ROS). It is not known(More)