Iron, Oxidative Stress and Early Neurological Deterioration in Ischemic Stroke

Abstract

Ischemic stroke is characterized by the disruption of cerebral blood flow, which produces a central core of dead neurons surrounded by a penumbra of damaged but partially functional neurons. Many factors are associated with such brain injury, including excitotoxicity and free radicals. Recent clinical studies have shown that high plasma ferritin levels are detrimental in acute ischemic stroke. As an iron-storage protein, ferritin can act both as a scavenger and as a donor of free iron, which is a source of hydroxyl radicals. Following disruption of the blood-brain barrier, the ferritin and the free iron that have accumulated in endothelial cells in brain capillaries, together with plasma ferritin, can enter the penumbra. Iron-dependent oxidative stress in the penumbra can lead to necrosis and further neurological deterioration following ischemic stroke. An excess of iron should be considered pathological in the ischemic brain. Therapeutic strategies for ischemic stroke should attempt to restore brain function within the penumbra. Consequently, the iron content of systemic stores should be measured, and anti-oxidant treatment should be considered when it is excessive.

Effect of Estrogen on Mitochondrial Function and Intracellular Stress Markers in Rat Liver and Kidney following Trauma-Hemorrhagic Shock and Prolonged Hypotension

“…This was not observed in E2-treated animals. Accumulation of free iron is known to be a potent inducer of oxidative stress (26). The combination of elevated electron transfer capacity and increased free iron levels was not accompanied by either activation of lipid peroxidation or increased nitrosylation/carbonylation of proteins in our samples.…”

Prevention of Both Neutrophil and Monocyte Recruitment Promotes Recovery after Spinal Cord Injury

“…Whereas excess nonheme iron is sequestered by intracellular iron storage and regulatory proteins, such as ferritin, ribonucleotide reductase, transferrin, and ceruloplasmin (Ponka, 2004), excessive accumulation may overwhelm these systems. Abnormal accumulation of nonheme iron occurs in a variety of pathological conditions such as ischemia (Carbonell and Rama, 2007;Davalos et al, 2000), hemorrhage Lee et al, 2010), Alzheimer's disease (Ong and Farooqui, 2005), Parkinson's disease (Crichton et al, 2010), traumatic brain injury (Yoneyama-Sarnecky et al, 2010), and SCI (Rathore et al, 2008). Moreover, antioxidants such as deferoxamine reduce nonheme iron accumulation, oxidative stress, and neuronal cell death in subarachnoid hemorrhage (Lee et al, 2010).…”

Blood-derived iron mediates free radical production and neuronal death in the hippocampal CA1 area following transient forebrain ischemia in rat

“…Iron overload has been implicated in free radical production and neuronal death in neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease (PD), and in stroke [5,33,44,53,61]. Under these pathological conditions, iron released from ironbinding proteins such as ferritin and cytochromes can catalyze free radical reactions by Fenton chemistry and Haber-Weiss cycle, resulting in damage to all types of biomolecules [24,31,39].…”