Candesartan Administration after Traumatic Brain Injury Alters Novel Molecular Pathways
Abstract
Traumatic Brain Injury (TBI) remains a major cause of morbidity within the military health system. Soldiers who have a TBI may experience changes in memory, mood, and cognitive function that can last for years after injury. However, despite numerous studies showing potential benefit of various treatments after TBI in animal models, at the present time there are limited treatment options available. Understanding the molecular mechanisms of these treatments in animal models may assist in determining pathways that are critical to drug efficacy and provide biomarkers of drug target engagement. The FDA approved angiotensin receptor blocker (ARB) candesartan, normally used to treat hypertension, has efficacy in improving molecular and functional recovery in mice after controlled cortical impact injury (CCI). A sub-hypotensive dose of candesartan can be administered 6 hours after injury and improve recovery one month after injury including improved learning and memory in mice models and reduction in lesion volumes. In addition to its antagonism at the angiotensin II type 1 receptor, candesartan is also a partial agonist of PPARy. Thus, candesartans efficacy in improving recovery from TBI could work through multiple pathways. This analysis is intended to elucidate potential mechanisms in which candesartan is producing this beneficial action.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 28, 2019
- Accession Number
- AD1181524
Entities
People
- Peter J Attilio
Organizations
- Uniformed Services University of the Health Sciences