Transcriptomics

Dataset Information

3

Common molecular signature of two neuroprotective agents


ABSTRACT: The current lack of proven pharmacological treatment options for traumatic brain injury (TBI) patients reflects the poor translation of successful preclinical studies in clinical trials. This may be due to poor choice of therapeutic agents based on incomplete knowledge of critical elements of neuroprotection. Our goal is to expedite discovery and translation of therapeutic agents that can improve functional outcome by identifying the common molecular profile of neuroprotective drugs. Since damage to the hippocampus is associated with TBI-induced deficits in learning and memory, we analyzed of the hippocampal transcriptional profiles of TBI rats treated with two clinically used drugs metyrapone and carbenoxolone, which have been shown to improve cognitive deficits in previous studies. Despite their different structures, we found that MT and CB have similar effects on several known biological pathways. The neuroprotective effects of these drugs are associated with a distinctive molecular signature which is characterized not by changes in expression of any individual gene but by a common global effect on multiple cell signaling pathways. These data suggest that drug treatments that induce a coordinated attenuation of multiple injury-induced cell signaling networks, both deleterious and protective, have high translational potential. There were 16 samples for array analysis, two biological replicates each for control (4 and 24 hour), TBI (4 and 24 hour), TBI plus MT (4 and 24 hour) and TBI plus CB (4 and 24 hour). Each biological sample, which is a pooled RNA sample (laser captured CA3 pyramidal neurons) from the hippocampus of 3-6 rats, was hybridized to duplicate arrays so that there were 32 gene arrays in this study.

ORGANISM(S): Rattus norvegicus  

SUBMITTER: Bridget Capra   Jeanna Crookshanks  Daniel Rojo  Helen Hellmich  Donald Prough  Brent Masel  Kristine Eidson  Deborah Boone  Douglas DeWitt  Michael Falduto 

PROVIDER: E-GEOD-31357 | ArrayExpress | 2012-12-23

SECONDARY ACCESSION(S): GSE31357PRJNA145945

REPOSITORIES: GEO, ArrayExpress

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