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View Project Hecker-1R01NS046591-01
Project Summary
Status: Public  
Publications: 1 Published
 		 
Project Detail Data Detail
Platform: Agilent MIAME Areas Compliance
Species: Rat Array Design Detail false
Organ/Tissue Type: brain Experiment Detail false
Organ Region: hippocampus Sample Detail false
Cell Type: primary neuronal cultures Hybridization Detail false
Study Type: pharmacogenomic Measurement Detail true
Disease/Condition: Anesthetics
Replicates: 0
Expected Samples:  
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Available Actions
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Investigator Contact Detail
Name James Hecker
Street Address: 3620 Hamilton Walk
Morgan 305
City, State/Province: Philadelphia , PA
Zip/Postal Code: 19104-6112
Country: United States
Work Phone: 215-349-5343
Fax: 215-349-5078
E-mail: heckerj@uphs.upenn.edu
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Proposal Detail
Grant: 1R01NS046591-01
Status: Public
Service Type: Start to Finish Profiling
IACUC: 708632
IACUC date: 2003-11-19
Study Relevance:
Diferent classes of common anesthetics used clinically and in vivo in experimental animals appear to cause anesthesia, that is, analgesia, amnesia, and unconsciousness, by different mechanisms. It is essential to understand differences in gene expression due to the different mechanisms of anesthetic action and their interactions with normal and patho-physiology in order to separate anesthetic effects from study effects.
Hypothesis:
We exposed rats to 1 MAC (Minimum Alvolar Concentration) equivalents of halothane and isoflurane in vivo in both acute and chronic exposures. After rigorous data analysis, a limited number of genes are expressed after halothane exposure, and no genes are identified as statistically up or down regulated after acute or chronic exposure to isoflurane. We hypothesize that with exposure concentrations up to 3 MAC and an acute recovery phase, a limited number of genes will be regulated by exposure to the commonly used inhalational anesthetics, isoflurane and halothane.
Specific Aim:
We will compare gene expression after clinically relevant 6 hour exposure of primary neuronal cell cultures to two commonly used inhalational anesthetics and one commonly used intraveneous sedative/hypnotic induction agen, propofol.
Experimental Procedure and Design:
This project will use primary neuronal cultures to allow us to expose neuronal cells to higher concentrations of commonly used clinical anesthetics that is feasible in the intact animal. Due to the cardiovascular depressant effects of these potent agents, exposure in intact animals to 3 MAC anesthesia for prolonged periods would require pharmacologic interventions to support the animal. Instead, rat pup primary cultures of cortical and hippocampal neurons will be harvested from Day 18 rat pups and grown in neuron-selective medium. Primary cell cultures will be exposed at D16 to 1, 1, and 3 Minimum Alvolar Concentration (MAC) equivalents of halothane, isoflurane, and sevoflurane inhalational anesthetics for 6 hours, allowed to recover for 6 hours, and cells will be lyzed and frozen at -80. After collection of all samples, mRNA will be isolated and purified for subsequent microarray by the Microarray Consortium. Groups will consist of unexposed controls, triplicates of 1 hour and three hour exposure, for each of three anesthetics.
Experimental Factors:
Conditions that are tested in the experiment. At least one is required. Experimental factors are the independent variables in the experiment.
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Experimental Factors is empty.
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Project Samples  This section lists the samples that are associated with this project. Individual sample details can be viewed by clicking on the View Sample icon to the right of the sample. If samples are selectable for analysis or for addition to a virtual
Samples associated with this project.
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Name Description Bio-Source Extracts  
control1 rat primary cortical neurons BioSource1 0
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Project Hybridizations 
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Hybridizations is empty.
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Project Reference Files
File Name Size
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