Neuroimaging Studies in Carbon Monoxide Intoxication

Mechanisms of CO intoxication2.1 Tissue hypoxia CO competes with oxygen in binding with hemoglobin to form carboxyhemoglobin.The affinity between CO and hemoglobin is 200 times higher than that of oxygen (Ernst and Zibrak 1998;Piantadosi 2002;Weaver 2009).The production of carboxyhemoglobin shifts the oxygen-hemoglobin curve to the left and dissociates oxygen from hemoglobin (Ernst and Zibrak 1998).These reactions consequently reduce oxygen delivery to tissues and result in a hypoxic microenvironment. Oxidative stressIn brief, CO intoxication leads to oxidative stress through the following mechanisms: 1. CO increases cytosolic heme levels leading to increased heme oxygenase-1 protein, causing intracellular oxidative stress and direct cellular injury (Ernst and Zibrak 1998; Weaver 2009).2. CO binds to cytochrome c oxidase and impairs mitochondrial function.Cytochrome c oxidase is one of the mitochondrial complexes involved in electric chain transport and is essential for energy production.Binding of CO to cytochrome c oxidase can lead to activation of hypoxia-inducible factor 1α or production of reactive oxygen species with direct cellular injury.Related downstream reactions include apoptosis, lipid peroxidation, lymphocyte proliferation, inflammation and necrosis (Weaver 2009).3. CO binds to platelet heme protein and induces biogenesis of nitric oxide peroxynitrite, consequently leading to enhanced adhesion of neutrophils to the vascular lining, neutrophil aggregation and release of myeloperoxidase.All of these reactions not only trigger inflammatory processes but also produce more reactive oxygen species (Ernst and Zibrak 1998; Weaver 2009). Reoxygenation injuryH 2 O 2 production has been noted to increase extensively in brain tissues during reoxygenation after CO intoxication (Zhang and Piantadosi 1992).Salicylate hydroxylation products and 2,3-and 2,5-dihydroxybenzoic acid are also significantly increased during reoxygenation.During this period, CO still binds to cytochrome c oxidase and inhibits the mitochondrial electron transport chain.If the reaction exists in iron-rich regions such as the basal ganglia, it causes persistent acidosis and active iron, which can further damage cells (Zhang and Piantadosi 1992). Mechanisms related to central nervous system (CNS) injury 2.4.1 Acute CNS injuryIn animal models, an initial cerebral blood flow increment after CO exposure is thought to maintain the baseline energy state (MacMillan 1975).A change of blood flow depends on both the reaction of the cerebrovasculature and cardiac function in CO intoxication.In either failure of cerebrovasculature dilatation or impairment of cardiac pumping function, there is no compensatory blood supply increase in the status of acute carboxyhemoglobin elevation and oxyhemoglobin reduction.(Raub and Benignus 2002).After initially compensated hyperperfusion, focal hypoperfusion has been noted in several studies (Choi, Lee et al. 1992;Choi and Lee 1993) which might be related to clinical manifestation (Sesay, Bidabe et al. 1996).Hypoperfusion over the basal ganglion (Sesay, Bidabe et al. 1996;Kao, Hung et al.

Hali tarjima qilinmagan