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Postoperative cognitive dysfunction (POCD) is a known phenomenon occurring after anesthesia with volatile anesthetics (VA), such as isoflurane. Recent reports suggest that VA interact with neurodegenerative disease-associated proteins including compounds with pathogenic relevance in Alzheimer disease (AD) and induce processes that may be linked to AD neuropathology. Unfortunately, our present understanding of the exact anesthetics' molecular mechanisms of action, their side effects on the brain, and their catenation with AD pathology is still limited. The present study analyzes the differential proteome of the hippocampus immediately after and 3 days after a 3-hour 1 minimal alveolar concentration isoflurane anesthesia in rats. Differential 2-dimensional electrophoresis, mass spectrometry, and functional network mapping were used to identify and functionally classify 12 different hippocampal proteins, which were significantly regulated after isoflurane anesthesia (6 up-regulated, 11 down-regulated with P<0.01). Induction of differential expression ranged from 0.05 (25-fold down-regulation) to 4.4 (4.4-fold up-regulation). Ten proteins were regulated immediately after and 7 proteins 3 days after isoflurane exposure. The proteome displays isoflurane-responsive protein candidates, which have also been shown to play a role in AD. They were grouped according to their key biologic activities, which showed that isoflurane affects selected biologic processes including synaptic plasticity, stress response, detoxification, and cytoskeleton in early and late recovery phases after anesthesia. These processes are also affected in AD. Results are discussed in view of AD, the toxicity mechanisms of isoflurane as well as the implications for our present understanding and conduction of clinical anesthesia.

During the course of sepsis, heart and liver dysfunction occurs in 20-30 of patients. Both septic cardiomyopathy and septic liver dysfunction have a high mortality and the underlying molecular pathophysiology remains unclear. The present study investigated changes in both cardiac and liver protein expression after cecal ligature and puncture (CLP) in a model of rat sepsis during a post-induction time course of 12, 24, and 48 hours. After approval by the local institutional review board, 62 male Wistar rats were investigated and assigned to three sham groups (n16) and three sepsis groups (n46). Rats of the sepsis groups and control groups were analyzed at specific time points after sepsis induction. Sepsis was induced by CLP and both heart and liver were removed after decapitation and prepared for proteomics. 2D-gel electrophoresis (2D-GE) and mass spectrometry (MS) as well as bioinformatic network pathway analysis (Ingenuity Pathways Analysis, IPA) were used to identify changes in protein expression between septic and non-septic samples. N27 rats of the sepsis group died (mortality 59 ) and no rat of the sham group died. More than 1,100 proteins could be discriminated with the proteomic method in both organs, of which 12 and 13 proteins were significantly regulated in heart and liver, respectively. 82 of the cardiac proteins could be associated with mitochondrial function. Both heart and liver proteins were primarily down-regulated in the course of sepsis. IPA associated the sets of differentially regulated proteins with proteins of heart and liver with compromised energy production. Sepsis induced significant alterations in the cardiac and liver proteome at 12, 24, and 48 hours after sepsis induction. Differentially regulated proteins of both organs mainly play a role in energy production. The diverse protein regulation indicates metabolic derangement and severely compromised cellular energy production following sepsis. Here, protein alterations may reflect septic organ dysfunction.

Parkinson's disease is the second most prevalent neurodegenerative disease and presents a particular anaesthetic challenge. The clinical features are described in detail, and recent advances in medical management and neurosurgical treatment options are highlighted.

Despite a decreased mortality from sepsis, the absolute number of sepsis-related deaths has actually increased during the last years. At present, there are no biological markers available that can reliably assist early clinical diagnosis and the prompt initiation of therapy. This study investigated the changes in serum protein expression in a coecal ligature and puncture model of rat sepsis at 12, 24, and 48 hours after the induction of sepsis using differential proteomics.

The cause of brain dysfunction during sepsis and septic encephalopathy is still under ongoing research. Sepsis induced changes in cerebral protein expression may play a significant role in the understanding of septic encephalopathy. The aim of the present study was to explore cerebral proteome alterations in septic rats. Fifty-six male Wistar rats were randomly assigned to a sepsis group (coecal ligature and puncture, CLP) or a control group (sham). Surviving rats were killed 24 or 48 hours after surgery and whole-brain lysates were used for two-dimensional gel electrophoresis and subsequent protein identification. Differentially expressed proteins were identified by mass spectrometry. Using the Ingenuity Pathways Analysis (IPA) tool, the relationship and interaction between the identified proteins was analyzed. Mortality was 53 % in septic rats. No rat of the control group was lost. More than 1,100 spots per gel were discriminated of which 29 different proteins were significantly (2-fold, P &lt; 0.01) changed: 24 proteins down-regulated after 24 hours; two proteins up-regulated and three down-regulated after 48 hours. IPA identified 11 of 35 differentially regulated proteins allocating them to an existing inflammatory pathway. In the analysis of septic rat brains, multiple differentially expressed proteins associated with metabolism, signaling, and cell stress can be identified via proteome analysis, that may help to understand the development of septic encephalopathy.

Sepsis is often complicated by encephalopathy, neuroendocrine dysfunction and cardiovascular autonomic failure. The cause of septic brain dysfunction is not fully understood. The aim of the present study is to explore whether septic brain dysfunction in a common septic model in the rat correlates with abnormalities either of local cerebral blood flow (LCBF) of defined brain areas or of whole brain blood flow (CBF). 45 male Wistar rats (320± 13 g) were randomly assigned to a sepsis group (31 rats, cecal ligature and puncture, CLP) or a control group (14 rats, sham operation). Of these 45 rats, 16 rats were used for blood analysis; the remaining 29 rats were used for CBF/LCBF measurements. LCBF measurements were performed 24h after initial surgery using quantitative autoradiography with 4-iodo[N-methyl-14C]antipy- rine, which allows to analyze CBF on a regional/local and global basis. In 42 different brain regions bilateral optical density measurements were performed. Septic rats (vs. control) presented tachycardia (507± 37 vs. 452± 44 min-1, P &lt; 0.05), leukocytopenia (2.96± 2.37 vs. 8.83± 2.97•109•L-1, P &lt; 0.05), hypocapnia (29.3± 4.6 vs. 36.4± 3.9 mmHg, P &lt; 0.05), and higher serum lactate concentrations (5.7± 3.9 vs. 2.2± 2.0 mmol•L-1, P &lt; 0.05). LCBF of all 42 areas, as well as, CBF (116± 59 vs. 115±52 mL•100g-1•min-1, n.s.) did not differ. The results showed that severe sepsis (mortality rate of 43 %) did not induce alterations in mean CBF and LCBF. It is concluded that brain dysfunction is not reflected in changes of CBF during severe sepsis.