Bioenergetics of cerebral ischemia: A cellular perspective

Hertz, Leif

doi:10.1016/j.neuropharm.2008.05.023

Cited by 166 publications

(146 citation statements)

References 411 publications

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“…This is in line with previous reports of severe brain injury [81]. Traumatic brain insult can lead to injury in both grey and white matter by application of severe physical pressure on neuronal cell bodies and axons, leading to disrupted cell integrity, such as rupture and shearing.…”

Section: Aetiology-related Injurysupporting

confidence: 93%

“…Traumatic brain insult can lead to injury in both grey and white matter by application of severe physical pressure on neuronal cell bodies and axons, leading to disrupted cell integrity, such as rupture and shearing. Axonal injury can lead to Wallerian degeneration and related processes [82], while severe white matter disturbance can also include injury to non-neuronal cells that support axonal and synaptic functioning, thereby affecting axon survival [81]. Non-traumatic insults can lead to structural brain injury via disruption of metabolic needs or other vital cell mechanisms in both grey and white matter [81].…”

Section: Aetiology-related Injurymentioning

confidence: 99%

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Structural brain injury in patients with disorders of consciousness: A voxel-based morphometry study

et al. 2016

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Main objective: Disorders of consciousness (DOC; encompassing coma, vegetative state/unresponsive wakefulness syndrome (VS/UWS) and minimally conscious state minus/plus (MCS-/+)) are associated with structural brain injury. The extent of this damage remains poorly understood and merits a detailed examination using novel analysis techniques. Research design/methods and procedures: This study used voxel-based morphometry (VBM) on structural magnetic resonance imaging scans of 61 patients with DOC to examine grey and white matter injury associated with DOC, time spent in DOC, aetiology and diagnosis. Main outcomes and results: DOC and time spent in DOC were found to be associated with widespread structural brain injury, although the latter did not correlate strongly with injury in the right cerebral hemisphere. Traumatic, as compared to non-traumatic aetiology, was related to more injury in the brainstem, midbrain, thalamus, hypothalamus, basal forebrain, cerebellum, and posterior corpus callosum. Potential structural differences were found between VS/ UWS and MCS and between MCS-and MCS+, but need further examination. Conclusions: The findings indicate that both traumatic and non-traumatic DOC are associated with widespread structural brain injury, although differences exist that could lead to aetiologyspecific treatment strategies. Furthermore, the high degree of atrophy occurring after initial brain injury prompts the development and use of neuroprotective techniques to potentially increase patients' chances of recovery. KeywordsVegetative state/unresponsive wakefulness syndrome, minimally conscious state, structural brain injury, voxel-based morphometry History

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Section: Aetiology-related Injurysupporting

confidence: 93%

Section: Aetiology-related Injurymentioning

confidence: 99%

Structural brain injury in patients with disorders of consciousness: A voxel-based morphometry study

et al. 2016

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“…Glucose is the main substrate for cerebral energy production (Hofmeijer and van Putten, 2012) and during stroke the oxygen carried by the blood is much less than that required for complete oxidation of its content of glucose. Under these conditions, glycolysis may persist after oxygen has been depleted, but the reduction of oxidative metabolism of glucose leads to decreased ATP levels, while ADP and AMP levels increase (Hertz, 2008), causing a disruption of ionic homeostasis (Hansen, 1985), opening of anion channels (Kimelberg and Mongin, 1998), plasma membrane depolarization (Lipton, 1999), release of glutamate through astrocytic hemichannels (Ye et al, 2003) and downregulation of glutamate transporters (Harvey et al, 2011). The impairment of glutamate transporters, in addition to their operation in the reverse mode, leads to an accumulation of glutamate in the extracellular space (Grewer et al, 2008) and a consequent overactivation of postsynaptic glutamate receptors.…”

Section: Brain Ischemiamentioning

confidence: 99%

Role of the ubiquitin–proteasome system in brain ischemia: Friend or foe?

Caldeira

Salazar

Curcio

et al. 2014

Progress in Neurobiology

114

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A B S T R A C TThe ubiquitin-proteasome system (UPS) is a catalytic machinery that targets numerous cellular proteins for degradation, thus being essential to control a wide range of basic cellular processes and cell survival. Degradation of intracellular proteins via the UPS is a tightly regulated process initiated by tagging a target protein with a specific ubiquitin chain. Neurons are particularly vulnerable to any change in protein composition, and therefore the UPS is a key regulator of neuronal physiology. Alterations in UPS activity may induce pathological responses, ultimately leading to neuronal cell death. Brain ischemia triggers a complex series of biochemical and molecular mechanisms, such as an inflammatory response, an exacerbated production of misfolded and oxidized proteins, due to oxidative stress, and the breakdown of cellular integrity mainly mediated by excitotoxic glutamatergic signaling. Brain ischemia also damages protein degradation pathways which, together with the overproduction of damaged proteins and consequent upregulation of ubiquitin-conjugated proteins, contribute to the accumulation of ubiquitincontaining proteinaceous deposits. Despite recent advances, the factors leading to deposition of such aggregates after cerebral ischemic injury remain poorly understood. This review discusses the current knowledge on the role of the UPS in brain function and the molecular mechanisms contributing to UPS dysfunction in brain ischemia with consequent accumulation of ubiquitin-containing proteins. Chemical inhibitors of the proteasome and small molecule inhibitors of deubiquitinating enzymes, which promote the degradation of proteins by the proteasome, were both shown to provide neuroprotection in brain ischemia, and this apparent contradiction is also discussed in this review. ß

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“…After reperfusion, oxygen levels may be restored but the brain remains vulnerable to further injury that can be perpetuated by multiple biological pathways, commonly referred to as secondary energy failure [14]. Neuronal and glial cells die as a result of one or more cell death pathways, for example, excitotoxicity, oxidative stress, cellular oedema and inflammation [15]. This brain damage develops over a period of days to weeks; therefore, a therapeutic window exists for treatment or intervention [16].…”

Section: Introductionmentioning

confidence: 99%

Phosphorylation of GFAP is Associated with Injury in the Neonatal Pig Hypoxic-Ischemic Brain

Sullivan

Miller

et al. 2012

Neurochem Res

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Glial fibrillary acidic protein (GFAP) is an intermediate filament protein expressed in the astrocytecytoskeleton that plays an important role in the structure and function of the cell. GFAP can be phosphorylated at six serine (Ser) or threonine (Thr) residues but little is known about the role of GFAP phosphorylation in physiological and pathophysiological states. We have generated antibodies against two phosphorylated GFAP (pGFAP) proteins: p8GFAP, where GFAP is phosphorylated at Ser-8 and p13GFAP, where GFAP is phosphorylated at Ser-13. We examined p8GFAP and p13GFAP expression in the control neonatal pig brain and at 24h and 72h after an hypoxic-ischemic (HI) insult. Immunohistochemistry demonstrated pGFAP expression in astrocytes with an atypical cytoskeletal morphology, even in control brains. Semi-quantitative western blotting revealed that p8GFAP expression was significantly increased at 24h post-insult in HI animals with seizures in frontal, parietal, temporal and occipital cortices. At 72h post-insult, p8GFAP and p13GFAP expression were significantly increased in HI animals with seizures in brain regions that are vulnerable to cellular damage (cortex and basal ganglia), but no changes were observed in brain regions that are relatively spared following an HI insult (brain stem and cerebellum). Increased pGFAP expression was associated with poor neurological outcomes such as abnormal encephalography (EEG) and neurobehaviour, and increased histological brain damage.Phosphorylation of GFAP may play an important role in astrocyte remodelling during development and disease and could potentially contribute to the plasticity of the central nervous system. 3

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Bioenergetics of cerebral ischemia: A cellular perspective

Cited by 166 publications

References 411 publications

Structural brain injury in patients with disorders of consciousness: A voxel-based morphometry study

Structural brain injury in patients with disorders of consciousness: A voxel-based morphometry study

Role of the ubiquitin–proteasome system in brain ischemia: Friend or foe?

Phosphorylation of GFAP is Associated with Injury in the Neonatal Pig Hypoxic-Ischemic Brain

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