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• W2324514343 abstract "BACKGROUND We have previously shown that addition of valproic acid (VPA; a histone deacetylase inhibitor) to hetastarch (Hextend [HEX]) resuscitation significantly decreases lesion size in a swine model of traumatic brain injury (TBI) and hemorrhagic shock (HS). However, the precise mechanisms have not been well defined. As VPA is a transcriptional modulator, the aim of this study was to investigate its effect on brain gene expression profiles. METHODS Swine were subjected to controlled TBI and HS (40% blood volume), kept in shock for 2 hours, and resuscitated with HEX or HEX + VPA (n = 5 per group). Following 6 hours of observation, brain RNA was isolated, and gene expression profiles were measured using a Porcine Gene ST 1.1 microarray (Affymetrix, Santa Clara, CA). Pathway analysis was done using network analysis tools Gene Ontology, Ingenuity Pathway Analysis, and Parametric Gene Set Enrichment Analysis. Real-time polymerase chain reaction was used to verify the key microarray findings. RESULTS A total of 1,668 probe sets mapping to 370 known genes were differentially expressed between the HEX and HEX + VPA groups. Expression of apoptotic genes differed between groups, and biologic function analysis predicted a significant downregulation of apoptosis (p = 1.29 × 10−12), cell death (p = 8.46 × 10−12), and necrosis (p = 9.07 × 10−11). Pathway analysis indicated a significant modulation of pathways involved in cell signaling, dendritic cell response, and the complement system. CONCLUSION This is the first high-throughput analysis of cerebral gene profiling following TBI + HS. It shows that treatment with VPA significantly alters early transcription of pathways related to cell survival, which may explain its neuroprotective effects." @default.
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• W2324514343 date "2014-12-01" @default.
• W2324514343 modified "2023-09-23" @default.
• W2324514343 title "Effect of pharmacologic resuscitation on the brain gene expression profiles in a swine model of traumatic brain injury and hemorrhage" @default.
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• W2324514343 doi "https://doi.org/10.1097/ta.0000000000000345" @default.
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