Time-dependent mitochondrial-mediated programmed neuronal cell death prolongs survival in sepsis*

Messaris, Evangelos; Memos, Nicholas; Chatzigianni, Emmy; Konstadoulakis, Manousos M.; Menenakos, Evangelos; Katsaragakis, Stylianos; Voumvourakis, Costas; Androulakis, George

doi:10.1097/01.ccm.0000135744.30137.b4

Cited by 63 publications

(36 citation statements)

References 30 publications

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“…Previous studies by Messaris et al (2004) have shown cells with apoptotic morphology in pyramidal cells of the CA1 region of the hippocampus, the cells of the choroid plexus, and the Purkinje cells of the cerebellum by hematoxylin and eosin staining and transmission electron microscopy. These modifications started at 6 h after CLP and increased in the late phases of sepsis.…”

Section: Discussionmentioning

confidence: 99%

Sepsis-Associated Encephalopathy: A Magnetic Resonance Imaging and Spectroscopy Study

Bozza

Garteiser

Oliveira

et al. 2009

J Cereb Blood Flow Metab

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Brain dysfunction is frequently observed in sepsis as a consequence of changes in cerebral structure and metabolism, resulting in worse outcome and reduced life-quality of surviving patients. However, the mechanisms of sepsis-associated encephalopathy development and a better characterization of this syndrome in vivo are lacking. Here, we used magnetic resonance imaging (MRI) techniques to assess brain morphology and metabolism in a murine sepsis model (cecal ligation and puncture, CLP). Sham-operated and CLP mice were subjected to a complete MRI session at baseline, 6 and 24 h after surgery. Accumulation of vasogenic edematic fluid at the base of the brain was observed in T 2 -weighted image at 6 and 24 h after CLP. Also, the water apparent diffusion coefficients in both hippocampus and cortex were decreased, suggesting a cytotoxic edema in brains of nonsurvival septic animals. Moreover, the N-acetylaspartate/choline ratio was reduced in brains of septic mice, indicating neuronal damage. In conclusion, noninvasive assessment by MRI allowed the identification of new aspects of brain damage in sepsis, including cytotoxic and vasogenic edema as well as neuronal damage. These findings highlight the potential applications of MRI techniques for the diagnostic and therapeutic studies in sepsis.

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Section: Discussionmentioning

confidence: 99%

Sepsis-Associated Encephalopathy: A Magnetic Resonance Imaging and Spectroscopy Study

Bozza

Garteiser

Oliveira

et al. 2009

J Cereb Blood Flow Metab

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show abstract

“…This translocation is considered a key step in the initiation of mitochondria-dependent apoptosis, since cytochrome c, once present in the cytoplasm, comprises an upstream signal in the apoptotic cascade (Polster and Fiskum, 2004). The presence of mitochondria-dependent neuronal apoptosis in sepsis is supported by studies showing increased free intracellular Ca 2 + (Zhan et al, 1996) and enhanced cytoplasmic cytochrome c immunoreactivity (Messaris et al, 2004) in experimentally septic animals. Accordingly, apoptotic neurons with degenerating mitochondria have been observed in several brain regions of experimentally septic animals and deceased septic patients, including the cerebral cortex and hippocampus (Papadopoulos et al, 1999;Vereker et al, 2000;Semmler et al, 2005;Barichello et al, 2006;Orihuela et al, 2006;Kafa et al, 2010), the cerebellum (Messaris et al, 2004;Barichello et al, 2006), and some autonomic centers in the brain stem (Sharshar et al, 2003(Sharshar et al, , 2004.…”

Section: Apoptosismentioning

confidence: 99%

Neuro-oxidative-nitrosative stress in sepsis

Berg

Møller

Bailey

2011

J Cereb Blood Flow Metab

136

109

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Neuro-oxidative-nitrosative stress may prove the molecular basis underlying brain dysfunction in sepsis. In the current review, we describe how sepsis-induced reactive oxygen and nitrogen species (ROS/RNS) trigger lipid peroxidation chain reactions throughout the cerebrovasculature and surrounding brain parenchyma, due to failure of the local antioxidant systems. ROS/RNS cause structural membrane damage, induce inflammation, and scavenge nitric oxide (NO) to yield peroxynitrite (ONOO À ). This activates the inducible NO synthase, which further compounds ONOO À formation. ROS/RNS cause mitochondrial dysfunction by inhibiting the mitochondrial electron transport chain and uncoupling oxidative phosphorylation, which ultimately leads to neuronal bioenergetic failure. Furthermore, in certain 'at risk' areas of the brain, free radicals may induce neuronal apoptosis. In the present review, we define a role for ROS/RNS-mediated neuronal bioenergetic failure and apoptosis as a primary mechanism underlying sepsis-associated encephalopathy and, in sepsis survivors, permanent cognitive deficits.

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“…A recent study has demonstrated that changes in brain mitochondrial function are essentially related to an increase in proton permeability across the inner mitochondrial membrane [7]. In addition, another recent study has shown mitochondrial-mediated apoptosis in the rat brain during septic encephalopathy [29]. Therefore, mitochondrial dysfunction may play a crucial role in the mechanism of septic encephalopathy.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA haplogroup R in the Han population and recovery from septic encephalopathy

et al. 2011

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In the Han population, mtDNA haplogroup R is a strong independent predictor of the outcome of septic encephalopathy, conferring an increased chance of neurological recovery compared with individuals with a non-R haplogroup. Our results provide potential insights into the mechanisms involved in septic encephalopathy, and reveal that the mtDNA haplogroup R is an independent predictor of the outcome of septic encephalopathy.

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Time-dependent mitochondrial-mediated programmed neuronal cell death prolongs survival in sepsis*

Cited by 63 publications

References 30 publications

Sepsis-Associated Encephalopathy: A Magnetic Resonance Imaging and Spectroscopy Study

Sepsis-Associated Encephalopathy: A Magnetic Resonance Imaging and Spectroscopy Study

Neuro-oxidative-nitrosative stress in sepsis

Mitochondrial DNA haplogroup R in the Han population and recovery from septic encephalopathy

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