Mitigating Traumatic Brain Injuries and Neurological Implications via the Immunometabolite Itaconate
Abstract
The proposed work described herein is directly responsive to the topic areas (Understand and Treat) of the Traumatic Brain Injury and Psychological Health Research Program. One of the major causes of death in the battlefield is traumatic brain injury (TBI), and this is worsened when the TBI is accompanied with severe hemorrhage; thus, one of the greatest opportunities to reduce mortality and morbidity in the battlefield scenario involves appropriate treatment of TBI concomitant to hemorrhage. These therapies need to provide fluid resuscitation and rapid restoration of the inadequate oxygen supply to the brain and the rest of the body. This proposal will test a novel target treatment based on the idea that the cellular energetic pathway is a key factor to better resuscitate from TBI with hemorrhage. The main goal of the present study is to find new ways to treat TBI in the presence of hemorrhage. To date, existing therapies for TBI in the presence of severe hemorrhage are severely limited and there is a great interest in therapeutically targeting the metabolism and the cellular response to reduce pressure, reduced perfusion, and limited oxygenation. Here, we aim to establish itaconate-induced alteration of metabolism as an important new, innovative, and untapped opportunity for therapeutic intervention to reduce cellular injury in TBI. Itaconate is easy to administer, water-soluble, and endogenously present in the human body. Taken together, adequate resuscitation with enhanced cellular energetic metabolism could be the key to increase survival from TBI in the presence of severe hemorrhage.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310388
Entities
People
- Pedro Cabrales
Organizations
- United States Army
- University of California, San Diego