Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcriptional effects of a 6h treatment with 2% isoflurane in the anterior cingulate cortex of the 24h old neonatal piglet brain

ABSTRACT: Exposure of the developing brain to general anesthesia during early infancy may adversely affect its neural and cognitive development. In a range of animal species early developmental exposure to general anaesthesia without surgery, induces an increase in brain cell death, reductions in neuro and synapto-genesis, a disruption to the expression of cognitively salient genes and deficits in cognitive function that persist throughout life. We examined the effects of the anesthetic isoflurane (2% concentration for 6h) without surgery on gene expression in the anterior cingulate cortex of the neonatal male piglet brain. The developing piglet brain demonstrates remarkable neurodevelopmental similarities to that seen in the human infant, which has led to extensive use as models of perinatal neural injury. Isoflurane induced significant disruption to the expression of 79 gene transcripts, of these 26 are important for the control of transcription and 23 are important for the mediation of neural plasticity, memory formation and recall. Overall this data may suggest novel additional mechanisms by which isoflurane may induce adverse neural and cognitive development by disrupting the expression of genes mediating activity dependent development of neural circuits, the predictive adaptive responses of the brain, memory formation and recall.

ORGANISM(S): Sus scrofa

SUBMITTER: Prof Nikki Robertson

PROVIDER: E-MTAB-5129 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Similar Datasets

Project description:Enterotoxigenic Escherichia coli (ETEC) strains that produce both heat-stable (ST) and heat-labile (LT) enterotoxins cause severe post-weaning diarrhea in piglets. However, the relative importance of the individual enterotoxins to the pathogenesis of ETEC infection is poorly understood. In this study, we investigated the effect on virulence of an F4+ ETEC strain when removing some or all of its enterotoxins. Several isogenic mutant strains were constructed that lack the expression of LT in combination with one or both types of ST enterotoxins (STa and/or STb). Host early immune responses induced by these mutant strains 4h after infection were compared to the wild type strain GIS26 Â (O149:F4ac+, Â LT+ Â STa+ Â STb+). At the same time, the immune response of this wild type ETEC strain was compared to the mock-infected control, demonstrating the expression of porcine inflammatory response genes. For these purposes, the small intestinal segment perfusion (SISP) technique and microarray analysis were used and results were validated by qRT-PCR. We also measured net fluid absorption of pig small intestinal mucosa 4h after infection with wild type ETEC, the mutant strains and PBS (mock-infected). These data indicate an important role for STb in inducing small intestinal secretion early after infection. The microarray analysis of the different mutant strains also revealed an important role for STb in ETEC-induced immune response by the significant differential regulation of immune mediators like matrix metalloproteinase 3, interleukin 1 and interleukin 17. We conclude that STb can play a prominent role in ETEC-induced secretion and early immune response. In three pigs, 6 different treatments were performed. These treatments consisted of 4 mutant enterotoxigenic Escherichia coli GIS26 strains, GIS26 wild type strain, or PBS control. Per pig, the small intestine was divided into 6 loops with an interloop in between to avoid cross-contamination. In conclusion, every pig received each of the 6 treatments ad random.

Project description:Background: The aim of this study is to improve our understanding of the mechanisms underlying the function of corticosteriods in the limb muscles of ICU patients with acute quadriplegic myopathy (AQM) by using a unique porcine ICU model, i.e., 5-day longitudinal experiments where animals are sedated, mechanically ventilated and exposed to factor triggering AQM that is hydrocortisone. Results: An increased expression of genes involved in kinase activity, cell cycle regulation and transcriptional regulation. A decreased expression in genes regulating heat shock proteins, cytoskeletal & sarcomeric and oxidative stress response were also apparent. Therefore, it appears that CS has an additive deleterious role in acute quadriplegic myopathywere also apparent. Conclusions: CS induced molecular mechanisms involving kinase activity and heat shock protein genes were forwarded as probable mechanisms underlying the decreased force generating capacity. Eight female domestic piglets (Sus scrofa, average body weight 26.4 kg) were used in this study. Piglets were immobilized by anesthesia and mechanically ventilated via a tracheotomy for a period of five days. During this study period, the animals were sedated using isoflurane inhalation (Abbott Laboratories, Chicago, Il, USA, 0.8 - 1.3% end-tidal concentration) supplemented by intravenous bolus doses of morphine and ketamine as needed. Core body temperature (blood) was maintained in the range of 38.5 - 40M-BM-0C by a servo controlled heating pad. The animals received intravenous crystalloid fluid (Ringeracetat) to maintain stable blood pressure and urinary output and a glucose infusion (Rehydrex, Fresenius Kabi, Stockholm, Sweden, 25 mg glucose /mL) in the range of 0.5 - 1.5 mg/kg/minute to decrease the effects of catabolism. Each animal received prophylactic streptomycin 750 mg/d and bensylpenicillin 600 mg/d (Streptocillin Vet, Boeringer-Ingelheim, Hellerup, Denmark). Arterial blood gas analysis as well as electrolytes and blood glucose levels were monitored regularly and kept in the normal range throughout the study period. A neuromuscular blocking agent (NMBA) was administered as a continuous infusion of pancuronium bromide 0.1mg/kg/h (Pavolun; Organon, Boxtel, The Netherlands) for 5days while a corticosteroid (CS) was given as bolus doses of hydrocortisone. Keywords: Treatment, immobilization, muscle function.

Project description:Background: Skeletal muscle wasting and impaired muscle function in response to mechanical ventilation and immobilization in intensive care unit (ICU) patients are clinically challenging partly due to (i) the poorly understood intricate cellular and molecular networks; and (ii) the unavailability of an animal model mimicking this condition. By employing a unique porcine model mimicking the conditions in the ICU with long-term mechanical ventilation and immobilization, we have analyzed the expression profile of skeletal muscle biopsies taken at three time points during a five-day period. Results: We have analyzed the expression profile of skeletal muscle biopsies taken at three time points during a five-day period. Among the differentially regulated transcripts, extracellular matrix, energy metabolism, sarcomeric proteins and LIM protein mRNA levels were down-regulated while ubiquitin proteasome system, cathepsins, oxidative stress responsive genes and heat shock proteins (HSP) mRNAs were up-regulated Conclusions: We conclude that induction of HSPs may play an inherent temporary protective mechanism in skeletal muscle in the early stages of immobilization and mechanical ventilation. The proposed molecular events leading to our final hypothesis are illustrated in the manuscript. Keywords: Treatment, immobilization, muscle function. Sixteen female domestic piglets (Sus scrofa, average body weight 26.5 kg) were used in this study. All piglets were immobilized by anesthesia and mechanically ventilated (Servo 900C, Siemens-Elema, Solna, Sweden). The first m. biceps femoris biopsies (day 1) were obtained from all animals, after administering anesthetics. During the five day study period, four animals were sedated using isoflurane inhalation (Abbott Laboratories, Chicago, Il, USA, 0.8 – 1.3% end-tidal concentration) supplemented by intravenous bolus doses of morphine and ketamine as needed. Biopsies from the m. biceps femoris were obtained on two further separate occasions (days 3 and 5) in these animals. Core body temperature (blood) was maintained in the range of 38.5 – 40°C by a servocontrolled heating pad. The animals received intravenous crystalloid fluid (Ringer’s acetate) to maintain stable blood pressure and urinary output and a glucose infusion (Rehydrex, Fresenius Kabi, Stockholm, Sweden, 25 mg glucose /mL) in the range of 0.5 – 1.5 mg/kg/minute to decrease the effects of catabolism. Each animal received prophylactic streptomycin 750 mg/d and benzylpenicillin 600 mg/d (Streptocillin Vet, Boeringer-Ingelheim, Hellerup, Denmark). Arterial blood gas analysis as well as electrolytes and blood glucose levels were monitored regularly and kept in the normal range throughout the study period.

Dataset Information

Transcriptional effects of a 6h treatment with 2% isoflurane in the anterior cingulate cortex of the 24h old neonatal piglet brain

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets