Alterations in Cerebral Metabolomics and Proteomic Expression during Sepsis

Hinkelbein, Jochen; Feldmann, Robert; Peterka, Anna; Schubert, Charlotte; Schelshorn, Dominik W.; Maurer, Martin H.; Kalenka, Armin

doi:10.2174/156720207782446388

Cited by 29 publications

(34 citation statements)

References 38 publications

(69 reference statements)

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“…These differences and changes can also be linked to biological events that provide clues to the pathogenesis of disease or mechanisms of drug action or toxicity using computational or bioinformatics models that can map and visualize network interactions (21)(22)(23)(24). Alternatively, as a complimentary approach to genomics and proteomics, metabolic imaging techniques (such as positron emission tomography or magnetic resonance spectroscopic imaging) can be used to translate noninvasive imaging protocols in humans (Figure 2).…”

Section: Metabolomics As a Component Of A Systems Biology Approach Tomentioning

confidence: 99%

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The Emerging Field of Quantitative Blood Metabolomics for Biomarker Discovery in Critical Illnesses

Serkova

Standiford²,

Stringer

2011

Am J Respir Crit Care Med

166

124

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Metabolomics, a science of systems biology, is the global assessment of endogenous metabolites within a biologic system and represents a "snapshot" reading of gene function, enzyme activity, and the physiological landscape. Metabolite detection, either individual or grouped as a metabolomic profile, is usually performed in cells, tissues, or biofluids by either nuclear magnetic resonance spectroscopy or mass spectrometry followed by sophisticated multivariate data analysis. Because loss of metabolic homeostasis is common in critical illness, the metabolome could have many applications, including biomarker and drug target identification. Metabolomics could also significantly advance our understanding of the complex pathophysiology of acute illnesses, such as sepsis and acute lung injury/acute respiratory distress syndrome. Despite this potential, the clinical community is largely unfamiliar with the field of metabolomics, including the methodologies involved, technical challenges, and, most importantly, clinical uses. Although there is evidence of successful preclinical applications, the clinical usefulness and application of metabolomics in critical illness is just beginning to emerge, the advancement of which hinges on linking metabolite data to known and validated clinically relevant indices. In addition, other important aspects, such as patient selection, sample collection, and processing, as well as the needed multivariate data analysis, have to be taken into consideration before this innovative approach to biomarker discovery can become a reliable tool in the intensive care unit. The purpose of this review is to begin to familiarize clinicians with the field of metabolomics and its application for biomarker discovery in critical illnesses such as sepsis.

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Section: Metabolomics As a Component Of A Systems Biology Approach Tomentioning

confidence: 99%

“…To date, most metabolomic data have been generated in experimental models, including sepsis (24,40,41) and inflammatory lung injury (42)(43)(44). These preclinical animal data provide clear Figure 4.…”

Section: Clinical Application Of Nmr-based Blood Quantitative Metabolmentioning

confidence: 99%

The Emerging Field of Quantitative Blood Metabolomics for Biomarker Discovery in Critical Illnesses

Serkova

Standiford²,

Stringer

2011

Am J Respir Crit Care Med

166

124

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“…In einer kürzlich publizierten Untersuchung konnte gezeigt werden, dass zahlreiche Proteine, die im Zusammenhang mit Zellmetabolismus, Signaltransduktion oder Stress stehen, im Rahmen einer späten Sepsis nach 24 und 48 h im Gehirn verändert sind und daher auch als potenzielle Markerproteine dienen könnten [16]. Wenngleich die Diagnose einer Sepsis per se nicht durch den Nachweis erhöhter Biomarker gestellt wird, können C-reaktives Protein (CRP), Prokalzitonin (PCT), S100β oder "neutron-specific enolase" (NSE) dennoch wichtige Hinweise auf eine vorhandene systemische Infektion bzw.…”

Section: Sepsisbezogene Veränderungen Im Gehirnunclassified

“…1). Für beide Versuchsansät-ze wurde die Gruppengröße von 16 Versuchstieren (Sepsisgruppe: n=10; ShamGruppe: n=6) aufgrund der in der Sepsisgruppe zu erwartenden Mortalitäts-rate [36] und der bisherigen Erfahrung im eigenen Labor gewählt [16,17]. Hierdurch wurde eine Anzahl von 6 Tieren/ Gruppe angestrebt.…”

Section: Sepsismodellunclassified

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Frühzeitige Veränderungen der Proteinexpression im Gehirn der Ratte bei Sepsis

2008

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The role of proteomics in understanding biological mechanisms of sepsis

Cao

Robinson

2014

Proteomics Clinical Apps

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Sepsis is a systemic inflammatory state caused by infection. Complications of this infection with multiple organ failure lead to more lethal conditions, such as severe sepsis and septic shock. Sepsis is one of the leading causes of US deaths. Novel biomarkers with high sensitivity and specificity may be helpful for early diagnosis of sepsis and for improvement of patient outcomes through the development of new therapies. Mass spectrometry-based proteomics offers powerful tools to identify such biomarkers and furthermore to give insight to fundamental mechanisms of this clinical condition. In this review, we summarize findings from proteomics studies of sepsis and how their applications have provided more understanding into the pathogenesis of septic infection. Literatures related to "proteomics", "sepsis", "systemic inflammatory response syndrome", "severe sepsis", "septic infection", and "multiple organ dysfunction syndrome" were searched using PubMed. Findings about neonatal and adult sepsis are discussed separately. Within the adult sepsis studies, results are grouped based on the models (e.g., human or animal). Across investigations in clinical populations and in rodent and mammalian animal models, biological pathways, such as inflammatory and acute phase response, coagulation, complement, mitochondrial energy metabolism, chaperones, and oxidative stress, are altered at the protein level. These proteomics studies have discovered many novel biomarker candidates of septic infection. Validation the clinical use of these biomarker candidates may significantly impact the diagnosis and prognosis of sepsis. In addition, the molecular mechanisms revealed by these studies may also guide the development of more effective treatments.

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Alterations in Cerebral Metabolomics and Proteomic Expression during Sepsis

Cited by 29 publications

References 38 publications

The Emerging Field of Quantitative Blood Metabolomics for Biomarker Discovery in Critical Illnesses

The Emerging Field of Quantitative Blood Metabolomics for Biomarker Discovery in Critical Illnesses

Frühzeitige Veränderungen der Proteinexpression im Gehirn der Ratte bei Sepsis

The role of proteomics in understanding biological mechanisms of sepsis

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