Mitochondrial Function in Apoptotic Neuronal Cell Death

Haeberlein, Samantha L. Budd

doi:10.1023/b:nere.0000014823.74782.b7

Cited by 57 publications

(34 citation statements)

References 114 publications

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“…Consistent with the loss of complex V, we found that mitochondrial ATP was also decreased during hypoxia. Mitochondria provide almost all the ATP necessary for normal neuronal functions and ATP has been identified as one of the key factors determining cellular apoptosis or necrosis: maintenance of ATP production is associated with apoptosis, whereas a rapid decline of mitochondrial function and ATP is associated with necrosis (20). In our case, normal ATP production was not restored after incubation of synaptosomes in 2% O 2 and in anoxia.…”

Section: Discussioncontrasting

confidence: 51%

The Effect of Mild and Severe Hypoxia on Rat Cortical Synaptosomes

2005

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Brain ischemia results in neuronal injury and neurological disability. The present study examined the effect of mild (6% O2) and severe (2% O2) hypoxia on mitochondria of rat cortical synaptosomes. During mild and severe hypoxia, JO2 and ATP production significantly decreased and mitochondrial membranes depolarized. Synaptosomal calcium concentration increased slightly, albeit not significantly. After a 1 h re-oxygenation period, JO2, ATP production and mitochondrial membrane potential returned to control levels in synaptosomes incubated in 6% O2. In synaptosomes incubated in 2% O2, however, the ATP production was not restored after re-oxygenation and intrasynaptosomal Ca2+ significantly increased. The results indicate that both mild and severe hypoxia influence the physiology of synaptosomal mitochondria; the modifications are reversible after mild hypoxia and but partly irreversible after severe hypoxia.

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Section: Discussioncontrasting

confidence: 51%

The Effect of Mild and Severe Hypoxia on Rat Cortical Synaptosomes

2005

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“…The mitochondrion has been shown to be a key participant in TBI-induced neuropathology, 16 and its dysfunction has serious implications for outcome following head injury. Indeed, compared with patients with marginal mitochondrial impairment, who demonstrate a good outcome, TBI patients with profound mitochondrial impairment have a poor prognosis.…”

Section: Mitochondriamentioning

confidence: 99%

Multifunctional Drugs for Head Injury

2009

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Summary: Traumatic brain injury (TBI) remains one of the leading causes of mortality and morbidity worldwide in individuals under the age of 45 years, and, despite extensive efforts to develop neuroprotective therapies, there has been no successful outcome in any trial of neuroprotection to date. In addition to recognizing that many TBI clinical trials have not been optimally designed to detect potential efficacy, the failures can be attributed largely to the fact that most of the therapies investigated have been targeted toward an individual injury factor. The contemporary view of TBI is that of a very heterogenous type of injury, one that varies widely in etiology, clinical presentation, severity, and pathophysiology. The mechanisms involved in neuronal cell death after TBI involve an interaction of acute and delayed anatomic, molecular, biochemical, and physiological events that are both complex and multifaceted. Accordingly, neuropharmacotherapies need to be targeted at the multiple injury factors that contribute to the secondary injury cascade, and, in so doing, maximize the likelihood of a successful outcome. This review focuses on a number of such multifunctional compounds that have shown considerable success in experimental studies and that show maximum promise for success in clinical trials.

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“…Ischemia-induced decrease in MPT is coupled with the release of cytochrome c from mitochondria to cytoplasm (Budd-Haeberlein, 2004). In this study, the hippocampal CA1 region was dissected at 48 hr after I/R and homogenized in buffer (20 mM HEPES, pH 7.5, 0.25 M sucrose, 10 mM KCl, 1.5 mM MgCl 2 , 1 mM EDTA, 1 mM EGTA, and 1 mM dithiothreitol) together with a protease inhibitor cocktail.…”

Section: Measurement Of Cytochrome C Releasementioning

confidence: 99%

“…V Cessation of blood flow and lack of oxygen supply in cerebral ischemia are known to cause neuronal excitation together with release of excitatory neurotransmitters (Ikemune et al, 1999). In turn, this can trigger a series of cellular events, including synaptic membrane depolarization, influx of calcium, increase in production of reactive oxygen species (ROS), mitochondrial dysfunction, and finally neuronal apoptosis (Nitatori et al, 1995;Nakamura et al, 1999;Hara et al, 2000;Kirino, 2000;Won et al, 2001;Budd-Haeberlein, 2004). Increase in ROS is known to cause oxidative damage to lipids, proteins, and DNA (Sun and Chen, 1998;Love, 1999;Lewen et al, 2000;Chan, 2001) and has been an important underlying factor in ischemia/reperfusion (I/R)-induced delayed neuronal death (DND; Kirino, 2000).…”

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confidence: 99%

Neuroprotective mechanisms of curcumin against cerebral ischemia-induced neuronal apoptosis and behavioral deficits

et al. 2005

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Increased oxidative stress has been regarded as an important underlying cause for neuronal damage induced by cerebral ischemia/reperfusion (I/R) injury. In recent years, there has been increasing interest in investigating polyphenols from botanical source for possible neuroprotective effects against neurodegenerative diseases. In this study, we investigated the mechanisms underlying the neuroprotective effects of curcumin, a potent polyphenol antioxidant enriched in tumeric. Global cerebral ischemia was induced in Mongolian gerbils by transient occlusion of the common carotid arteries. Histochemical analysis indicated extensive neuronal death together with increased reactive astrocytes and microglial cells in the hippocampal CA1 area at 4 days after I/R. These ischemic changes were preceded by a rapid increase in lipid peroxidation and followed by decrease in mitochondrial membrane potential, increased cytochrome c release, and subsequently caspase-3 activation and apoptosis. Administration of curcumin by i.p. injections (30 mg/kg body wt) or by supplementation to the AIN76 diet (2.0 g/kg diet) for 2 months significantly attenuated ischemia-induced neuronal death as well as glial activation. Curcumin administration also decreased lipid peroxidation, mitochondrial dysfunction, and the apoptotic indices. The biochemical changes resulting from curcumin also correlated well with its ability to ameliorate the changes in locomotor activity induced by I/R. Bioavailability study indicated a rapid increase in curcumin in plasma and brain within 1 hr after treatment. Together, these findings attribute the neuroprotective effect of curcumin against I/R-induced neuronal damage to its antioxidant capacity in reducing oxidative stress and the signaling cascade leading to apoptotic cell death.

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Mitochondrial Function in Apoptotic Neuronal Cell Death

Cited by 57 publications

References 114 publications

The Effect of Mild and Severe Hypoxia on Rat Cortical Synaptosomes

The Effect of Mild and Severe Hypoxia on Rat Cortical Synaptosomes

Multifunctional Drugs for Head Injury

Neuroprotective mechanisms of curcumin against cerebral ischemia-induced neuronal apoptosis and behavioral deficits

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