Hypothermia and valproic acid activate prosurvival pathways after hemorrhage

The Journal of Surgical Research
Ted BambakidisHasan B Alam

Abstract

Therapeutic hypothermia (hypo) and valproic acid (VPA, a histone deacetylase inhibitor) have independently been shown to be protective in models of trauma and hemorrhagic shock but require logistically challenging doses to be effective. Theoretically, combined treatment may further enhance effectiveness, allowing us to use lower doses of each modality. The aim of this study was to determine whether a combination of mild hypo and VPA treatments would offer better cytoprotection compared with that of individual treatments in a hemorrhage model. Male Sprague-Dawley rats were subjected to 40% volume-controlled hemorrhage, kept in shock for 30 min, and assigned to one of the following treatment groups: normothermia (36°C-37°C), hypo (30 ± 2°C), normothermia + VPA (300 mg/kg), and hypo + VPA (n = 5 per group). After 3 h of observation, the animals were sacrificed, liver tissue was harvested and subjected to whole cell lysis, and levels of key proteins in the prosurvival Akt pathway were measured using Western blot. Activation of the proapoptotic protein cleaved caspase-3 was significantly lower in the combined treatment group relative to normothermia (P < 0.05). Levels of the prosurvival Bcl-2 was significantly higher in the combined...Continue Reading

References

Feb 1, 1995·The Journal of Trauma·A SauaiaP T Pons
Aug 30, 2003·Journal of the American College of Surgeons·Vadim GushchinElena Koustova
Dec 8, 1956·Nature·J GIAJA, J RADULOVIC
Jul 28, 2004·Journal of Molecular and Cellular Cardiology·Gavin Y OuditPeter H Backx
May 25, 2007·Annals of Surgery·John B HolcombFrank K Butler
Apr 9, 2008·Journal of Inherited Metabolic Disease·M F B SilvaI Tavares de Almeida
Jul 25, 2009·Surgery·Hasan B AlamGeorge C Velmahos
Aug 5, 2009·Journal of the American College of Surgeons·Fahad ShujaHasan B Alam
Oct 3, 2012·The Journal of Trauma and Acute Care Surgery·Hasan B AlamUNKNOWN HYPOSTAT workshop participants
Nov 29, 2012·The Journal of Trauma and Acute Care Surgery·Guang JinHasan B Alam
May 21, 2013·The Journal of Surgical Research·Marlin Wayne CauseyMatthew Martin
Oct 2, 2013·Journal of Pediatric Neurosciences·Neera ChaudhryVinod Puri
Oct 19, 2013·The Journal of Surgical Research·John O HwabejireHasan B Alam
Jul 23, 2014·The Journal of Trauma and Acute Care Surgery·Ting ZhaoHasan B Alam

❮ Previous
Next ❯

Citations

Feb 6, 2018·The Journal of Trauma and Acute Care Surgery·Panpan ChangHasan B Alam
Aug 10, 2019·Anesthesia and Analgesia·Ettore CrimiClaudio Napoli
Jan 3, 2019·Shock·Aaron M WilliamsHasan B Alam

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adherens Junctions

An adherens junction is defined as a cell junction whose cytoplasmic face is linked to the actin cytoskeleton. They can appear as bands encircling the cell (zonula adherens) or as spots of attachment to the extracellular matrix (adhesion plaques). Adherens junctions uniquely disassemble in uterine epithelial cells to allow the blastocyst to penetrate between epithelial cells. Discover the latest research on adherens junctions here.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Cadherins and Catenins

Cadherins (named for "calcium-dependent adhesion") are a type of cell adhesion molecule (CAM) that is important in the formation of adherens junctions to bind cells with each other. Catenins are a family of proteins found in complexes with cadherin cell adhesion molecules of animal cells: alpha-catenin can bind to β-catenin and can also bind actin. β-catenin binds the cytoplasmic domain of some cadherins. Discover the latest research on cadherins and catenins here.

Brain Injury & Trauma

brain injury after impact to the head is due to both immediate mechanical effects and delayed responses of neural tissues.

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis