Molecular Mechanisms of Acidosis-Mediated Damage

Siesjö, Bo K.; Katsura, Ken‐ichiro; Kristián, Tibor; Li, P.-A.; Siesjö, Peter

doi:10.1007/978-3-7091-9465-2_2

Cited by 75 publications

(88 citation statements)

References 52 publications

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“…The intracellular acidification by excess CO 2 , and the dysfunction of active ion pumps by the loss of ATP, is considered a primary cause of cell death (Siesjo et al, 1996). The possibility has been raised that the intracellular acidification comprises an event in the process of apoptosis, such as an increase of ICE-like protease activity (Furlong et al, 1997;Matsuyama et al, 2000).…”

Section: Acidosismentioning

confidence: 99%

Cellular and Molecular Pathways of Ischemic Neuronal Death

Won¹,

Kim²,

Gwag³

2002

BMB Reports

201

172

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Three routes have been identified triggering neuronal death under physiological and pathological conditions. Excess activation of ionotropic glutamate receptors cause influx and accumulation of Ca 2+ and Na + that result in rapid swelling and subsequent neuronal death within a few hours. The second route is caused by oxidative stress due to accumulation of reactive oxygen and nitrogen species. Apoptosis or programmed cell death that often occurs during developmental process has been coined as additional route to pathological neuronal death in the mature nervous system. Evidence is being accumulated that excitotoxicity, oxidative stress, and apoptosis propagate through distinctive and mutually exclusive signal transduction pathway and contribute to neuronal loss following hypoxic-ischemic brain injury. Thus, the therapeutic intervention of hypoxic-ischemic neuronal injury should be aimed to prevent excitotoxicity, oxidative stress, and apoptosis in a concerted way.

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Section: Acidosismentioning

confidence: 99%

Cellular and Molecular Pathways of Ischemic Neuronal Death

Won¹,

Kim²,

Gwag³

2002

BMB Reports

201

172

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show abstract

“…75,81 Acidosis can accelerate free radical production, interfere with the intracellular signal transduction pathway, activate endonucleases, and contribute to mitochondrial damage. 82 Mitochondrial dysfunction during ischemia leads to further production of free radicals, which may then trigger secondary mitochondrial failure and cell death. 75 Secondary damage to mitochondria and brain tissue may occur after a delay of hours or days.…”

Section: Bioenergetic Failurementioning

confidence: 99%

Pathophysiology and therapeutic targets for ischemic stroke

Levine

2004

Clin Cardiol

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Summary:The increased risk for stroke among those who have had a previous stroke or transient ischemic attack (TIA) and the tremendous burden of disability among stroke sufferers make both primary and secondary preventative strategies imperative. An understanding of the pathophysiology of stroke and TIA can help identify appropriate therapeutic targets. Stroke and Heart Disease Shared Pathology and Risk FactorsUnderlying atherosclerosis, which plays a significant role in both ischemic stroke and myocardial infarction (MI), is similar in both conditions. Despite this similarity, however, these two disease states are characterized by distinct differences in pathophysiology that go beyond the mere location of the thrombus. Coronary artery lesions tend to be more fibrotic than those found in the cerebral vasculature. 1, 2 Stroke patients are an extremely heterogeneous group compared with those who have had an MI. There is a variety of sources for the thrombus as well as numerous areas in which ischemic occlusion can occur. The evolution of the consequences of the ischemic event also differs in stroke and MI. Stroke pathology pursues a much longer course than MI, with secondary damage and metabolic sequelae occurring at times up to a month after the initial event. 3 The neurological complications and clinical manifestations following a stroke vary considerably as well, depending upon which areas of the brain were affected and to what degree. Patients may suffer from any combination of cognitive, motor, visual, sensory, language, speech, or mood deficits. Deficits can be discrete or global. Finally, despite the pervasive notion that stroke patients are at increased risk for acute MI, in up to 75% of stroke survivors a subsequent cardiovascular event could be another stroke. 4 However, both stroke and MI share many risk factors. Hypertension and diabetes mellitus are important modifiable risk factors for both stroke and heart failure. 5 In fact, cardiovascular disease, including stroke and heart disease, is the primary cause of death in persons with diabetes. 6 Hyperlipidemia is an accepted risk factor for coronary artery disease, and its contribution to ischemic stroke is also important. 7-10 Data from studies indicate that use of the beta-hydroxy-betamethylglutaryl-CoA reductase inhibitors or statins (cholesterol-lowering drugs) offers stroke protection and reduces the amount of carotid atheroma, although the mechanisms involved are unclear. [7][8][9][10] Lifestyle factors, such as obesity and smoking, and use of a number of chemical substances, including alcohol and both legal and illegal drugs, have been associated with cardiovascular disease in general and stroke in particular. 7,11,12 Some prescription medications have been associated with an increased incidence of stroke. In the past, early-generation oral contraceptives were found to increase stroke risk, 13 and controversy has surrounded hormone replacement therapy (HRT), with recent findings from the Hormone and Estrogen/progestin Replacement Study (HERS) a...

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“…17 From a pathophysiologic basis, elevated glucose levels allow a higher substrate availability for the production of lactate during the anaerobic metabolism consequent with cerebral ischemia. 18,19 Intracellular lactic acidosis interferes with glycolysis, protein synthesis, and enzyme function, among other intracellular processes. 20 In addition, hyperglycemia has also been demonstrated during cerebral ischemia to increase the release of the excitotoxic amino acids glutamate and aspartate.…”

mentioning

confidence: 99%

“…17 D'un point de vue physiopathologique, les niveaux élevés de glucose permettent une disponibilité des substrats plus élevée pour la production de lactate pendant un métabolisme anaérobique suite à une ischémie cérébrale. 18,19 L'acidose lactique intracellulaire interfère avec la glycolyse, la synthèse des protéines et la fonction enzymatique, parmi d'autres processus intracellulaires. 20 En outre, il a également été démontré que l'hyperglycémie facilite la libération des acides aminés excitotoxiques glutamate et aspartate pendant l'ischémie cérébrale.…”

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Hyperglycemia and postoperative cognitive dysfunction: another call for better glycemic control?

Grocott

2008

Can J Anesth/J Can Anesth

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Molecular Mechanisms of Acidosis-Mediated Damage

Cited by 75 publications

References 52 publications

Cellular and Molecular Pathways of Ischemic Neuronal Death

Cellular and Molecular Pathways of Ischemic Neuronal Death

Pathophysiology and therapeutic targets for ischemic stroke

Hyperglycemia and postoperative cognitive dysfunction: another call for better glycemic control?

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