Molecular mechanisms for protection against terminal blood loss
Research type
Research Study
Full title
Defining molecular mechanisms and new therapeutics for protection against terminal blood loss
IRAS ID
161018
Contact name
Robin Simon Brooke Williams
Contact email
Sponsor organisation
Royal Holloway University of London
Research summary
Trauma or injury is often associated with bleeding, providing the leading cause of death in trauma patients in both civilian and military populations. This highlights a need for the development of a treatment that can stabilize hemorrhaging patients between injury and hospital care. Several recent studies have suggested that pharmacological intervention can prevent terminal blood loss-related death over 4 hours. One of these drugs, valproic acid, has been shown to protect against terminal blood loss in several animal models. The mechanism of valproic acid in this role is unclear, although it has been suggested to act via the regulation of cell signalling and by histone modification.
We have sought to characterize the molecular mechanism of valproic acid in protection against terminal blood loss. These experiments have identified a likely molecular pathway activated during terminal blood loss that is rescued by valproic acid. This result provides a highly significant breakthrough in defining the mechanism of action of valproic acid in the prevention of terminal blood loss.
Our data so far has provided a potentially exciting step forward in our understanding of the molecular events involved in terminal blood loss, and potential treatments. To ratify our discoveries, it is important to show similar signalling events and control through therapy is evident in human primary tissue. As such, we are requesting access to primary [placental and liver] tissue that will provide a suitable human model for experimental recapitulation. Cells derived from this tissue will be grown in cell culture for a maximum of eight weeks. Cells will then be exposed to conditions similar to that of terminal blood loss, in the presence or absence of pharmaceutical compounds, and cells will be analyzed for signalling changes. During these experiments, cell will be lysed and analyzed by Western analysis.
REC name
North of Scotland Research Ethics Committee 1
REC reference
14/NS/1050
Date of REC Opinion
17 Sep 2014
REC opinion
Further Information Favourable Opinion