Skip Navigation LinksHome > Published Ahead-of-Print > Effect of pharmacologic resuscitation on the brain gene expr...
Journal of Trauma and Acute Care Surgery:
doi: 10.1097/TA.0000000000000345
Original Article: PDF Only

Effect of pharmacologic resuscitation on the brain gene expression profiles in a swine model of traumatic brain injury and hemorrhage.

Dekker, Simone E. BSc; Bambakidis, Ted MSc; Sillesen, Martin MD; Liu, Baoling MD; Johnson, Craig N. PSM; Jin, Guang MD, PhD; Li, Yongqing MD, PhD; Alam, Hasan B. MD

Published Ahead-of-Print
Collapse Box

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 x 10-12), cell death (p = 8.46 x 10-12), and necrosis (p = 9.07 x 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.

(C) 2014 Lippincott Williams & Wilkins, Inc.

Follow Us


Login

Article Tools

Share

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.