Biochemical changes associated with selective neuronal death following short-term cerebral ischaemia

Sims, Neil R.; Zaidan, Emad

doi:10.1016/1357-2725(95)00026-l

Cited by 92 publications

(72 citation statements)

References 136 publications

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“…3A), while corresponding CMRO 2 measurements were considerably lower than baseline (1.75 Ϯ 0.18 compared with 2.61 Ϯ 0.11 ml O 2 ⅐min Ϫ1 ⅐100 g Ϫ1 ). These results suggest that the reductions in CMRO 2 cannot be explained solely by reductions in electrocortical activity and may imply that basic cellular mechanisms, such as protein synthesis, may be downregulated following hypoxiaischemia (34).…”

Section: Discussionmentioning

confidence: 84%

Cerebral metabolic rate of oxygen and amplitude-integrated electroencephalography during early reperfusion after hypoxia-ischemia in piglets

Tichauer¹,

Elliott²,

Hadway³

et al. 2009

Journal of Applied Physiology

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Tichauer KM, Elliott JT, Hadway JA, Lee T, St. Lawrence KS. Cerebral metabolic rate of oxygen and amplitude-integrated electroencephalography during early reperfusion after hypoxia-ischemia in piglets. J Appl Physiol 106: 1506 -1512. First published March 19, 2009 doi:10.1152/japplphysiol.91156.2008.-The therapeutic window following perinatal hypoxia-ischemia is brief, and early clinical signs of injury can be subtle. Electroencephalography (EEG) represents the most promising early diagnostic of hypoxia-ischemia; however, some studies have questioned the sensitivity and specificity of EEG. The present study investigated the use of both near-infrared spectroscopy (NIRS) measurements of the cerebral metabolic rate of oxygen (CMRO 2) and amplitude-integrated EEG (aEEG) to detect the severity of hypoxia-ischemia after 1 h of reperfusion in newborn piglets (10 insult, 3 control). The CMRO2 was measured before and after 1 h of reperfusion from hypoxia-ischemia, the duration of which was varied from piglet to piglet with a range of 3-24 min, under fentanyl/nitrous oxide anesthesia to mimic awake-like levels of cerebral metabolism. EEG data were collected throughout the study. On average, the CMRO2 and mean aEEG background signals were significantly depressed following the insult (P Ͻ 0.05). Mean CMRO 2 and mean aEEG background were 2.61 Ϯ 0.11 ml O2 ⅐ min Ϫ1 ⅐ 100 g Ϫ1 and 20.4 Ϯ 2.7 V before the insult and 1.58 Ϯ 0.09 ml O2⅐min Ϫ1 ⅐100 g Ϫ1 and 11.8 Ϯ 2.9 V after 1 h of reperfusion, respectively. Both CMRO2 and aEEG displayed statistically significant correlations with duration of ischemia (P Ͻ 0.05; r ϭ 0.71 and r ϭ 0.89, respectively); however, only CMRO2 was sensitive to milder injuries (Ͻ5 min). This study highlights the potential for combining NIRS measures of CMRO2 with EEG in the neonatal intensive care unit to improve early detection of perinatal hypoxia-ischemia. near-infrared spectroscopy; piglet; hypoxia-ischemia; electroencephalography PERINATAL HYPOXIC-ISCHEMIC encephalopathy is a substantial cause of infant mortality and morbidity. It remains a detrimental factor in roughly 1 of every 500 live term births in developed nations, leading to long-term neurological and developmental disabilities (20). Recent clinical trials have demonstrated that the incidence of death and disability from hypoxia-ischemia in newborns can be significantly reduced by initiating treatment strategies, hypothermia, for example, after birth and within a 6-h therapeutic window (9,11,14,32). Due to the brevity of the therapeutic window, early detection of injury and early determination of those infants who are likely candidates for treatment are crucial (15). In this regard, traditional early indicators of brain injury, including Apgar scores, umbilical artery acidosis, and fetal heart rate monitoring, suffer from poor specificity (7, 31), and more specific indicators of injury, such as magnetic resonance imaging and spectroscopy, are insensitive or difficult to implement within the therapeutic window (6, 21).To this point, the most...

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Section: Discussionmentioning

confidence: 84%

Cerebral metabolic rate of oxygen and amplitude-integrated electroencephalography during early reperfusion after hypoxia-ischemia in piglets

Tichauer¹,

Elliott²,

Hadway³

et al. 2009

Journal of Applied Physiology

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“…It would be of interest to examine the progression of neuronal injury that occurred after a brief interruption of blood flow to the brain and define the changes associated with cerebral ischemia and reperfusion, to identify capable therapies that would modify the extent of neuronal damage. Such an investigation seems to be highly important in the clinic, because if the flow interruption is not reversed during the first hour, the cells within the most severely ischemic region will inevitably die [1]. Because there is a narrow therapeutical window after cerebral ischemia to reverse or interfere with the progression of neuronal damage, the search for effective agents capable of reducing the progression of neuronal injury occurring after ischemia further supports the research.…”

Section: Introductionmentioning

confidence: 87%

“…The pathogenesis of cerebral ischemia has been associated with depletion of cellular energy sources, a massive release of excitatory amino acids, mitochondrial dysfunction and formation of reactive oxygen species, that contribute to the oxidative damage [1]. The brain area surrounding the ischemic core, the penumbra area, is characterized by a decrement in glucose supply and further neurodegeneration resulting from hypoglycemia.…”

Section: Introductionmentioning

confidence: 99%

Influence of the antioxidants vitamin E and idebenone on retinal cell injury mediated by chemical ischemia, hypoglycemia, or oxidative stress

Rego

Santos

Oliveira

1999

Free Radical Biology and Medicine

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Abstract-A role for the antioxidants vitamin E and idebenone in decreasing retinal cell injury, after metabolic inhibition induced by chemical ischemia and hypoglycemia, was investigated and compared with oxidative stress conditions. Preincubation of the antioxidants, vitamin E (20 M) and idebenone (10 M), effectively protected from retinal cell injury after oxidative stress or hypoglycemia, whereas the protection afforded after postincubation of both antioxidants was decreased. Delayed retinal cell damage, mediated by chemical ischemia, was attenuated at 10 or 12 h postischemia, only after exposure to the antioxidants during all the experimental procedure. An antagonist of the N-methyl-D-aspartate (NMDA) receptors, an inhibitor of nitric oxide synthase (NOS) or a blocker of L-type Ca 2ϩ channels were ineffective in reducing cell injury induced by chemical ischemia, hypoglycemia or oxidative stress. Oxidative stress and hypoglycemia increased (about 1.2-fold) significantly the fluorescence of the probe DCFH 2 -DA, that is indicative of intracellular ROS formation. Free radical generation detected with the probe dihydrorhodamine 123 (DHR 123) was enhanced after oxidative stress, chemical ischemia or hypoglycemia (about 2-fold). Nevertheless, the antioxidants vitamin E or idebenone were ineffective against intracellular ROS generation. Cellular energy charge decreased greatly after chemical ischemia, was moderately affected after hypoglycemia, but no significant changes were observed after oxidative stress. Preincubation with vitamin E prevented the changes in energy charge upon 6 h posthypoglycemia. We can conclude that irreversible changes occurring during chemical ischemia mainly reflect the alterations taking place at the ischemic core, whereas hypoglycemia situations may reflect changes occurring at the penumbra area, whereby vitamin E or idebenone may help to increase cell survival, exerting a beneficial neuroprotective effect.

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“…This response is generated following an interaction of glutamate with receptors composing cation channels. Excessive activation of glutamate receptors can result in neuronal dysfunction and death, a process called excitotoxicity [5] . There is an excess of glutamate and glutamatergic activity in certain neurodegenerative diseases.…”

Section: Ionotropic and Metabotropic Glutamate Receptorsmentioning

confidence: 99%

Molecular mechanisms of excitotoxicity and their relevance to pathogenesis of neurodegenerative diseases

2009

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A pivotal role for excitotoxicity in neurodegenerative diseases is gaining increasingly more acceptance, but the underlying mechanisms through which it participates in neurodegeneration still need further investigation. Excessive activation of glutamate receptors by excitatory amino acids leads to a number of deleterious consequences, including impairment of calcium buffering, generation of free radicals, activation of the mitochondrial permeability transition and secondary excitotoxicity. Recent studies implicate excitotoxicity in a variety of neuropathological conditions, suggesting that neurodegenerative diseases with distinct genetic etiologies may share excitotoxicity as a common pathogenic pathway. Thus, understanding the pathways involved in excitotoxicity is of critical importance for the future clinical treatment of many neurodegenerative diseases. This review discusses the current understanding of excitotoxic mechanisms and how they are involved in the pathogenesis of neurodegenerative diseases.

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Biochemical changes associated with selective neuronal death following short-term cerebral ischaemia

Cited by 92 publications

References 136 publications

Cerebral metabolic rate of oxygen and amplitude-integrated electroencephalography during early reperfusion after hypoxia-ischemia in piglets

Cerebral metabolic rate of oxygen and amplitude-integrated electroencephalography during early reperfusion after hypoxia-ischemia in piglets

Influence of the antioxidants vitamin E and idebenone on retinal cell injury mediated by chemical ischemia, hypoglycemia, or oxidative stress

Molecular mechanisms of excitotoxicity and their relevance to pathogenesis of neurodegenerative diseases

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