Host - HIF- 1alpha Pathway And Hypoxia: In Vitro Studies And Mathematical Model
Abstract
Episodes of hypoxia were implicated in F-22 pilots after training missions in which questions about pilot exposures and mission accomplishment were raised. These episodes identified data gaps in the understanding the complexities of exposures to pilots in high performance aircraft including variations in oxygen availability and physiological usage was in question. We therefore undertook a project need to understand how hypoxia relates to alterations in brain functioning. Responses to hypoxia take place at multiple levels. The initial response is through the carotid body altering physiology (breathing, blood flow). Tissue level responses involve regulating demand for oxygen through altered function. Key to understanding these responses both at the physiological and tissue (brain) level are oxygen sensing pathways, particularly those involving HIF-1. These linked pathways need to be understood mechanistically and quantitatively. In vitro studies are useful for elucidating elements of these processes. These changes in complex pathways need to be integrated and applied (extrapolated) to relevant human exposure scenarios in order to assess the relevance of hypoxia occurrences into the abovementioned AF issues.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 30, 2016
- Accession Number
- AD1022155
Entities
People
- David R. Mattie
- Deirdre A. Mahle
- Elaine A. Merrill
- Kyung O. Yu
- Meghan K. Makley
- Molly E. Chapleau
- Peter Robinson
- R. A. James