Neuroprotective Mechanism of DMF/MMF Associated With CAA-Related Pathology After TBI
Abstract
The effect of fumaric acid esters (DMF/MMF) on the CAA outcomes after TBI is postulated to be positive, though several discrepancies remain. Nrf2 is one of the master regulators of redox and inflammation. DMF and its metabolite MMF hold antioxidative and anti-inflammatory by activating Nrf2. Thus, we expect that understanding the unique and respective roles of DMF and MMF on Nrf2 on CAA neuroprotection is essential, and its validation in TBI would strengthen their potential use for veterans and active military people. However, whether DMF has superior beneficial effects over MMF or vice versa is unclear. Furthermore, whether the therapeutic window would defer from acute TBI over a repetitive concussion-like brain insult leading to CAA needs to be tested. Considering these knowledge gaps, we aim to start answering these questions using preclinical models. We maintain/renewed the animal protocols approved by the Institutional IACUC from 07/18/2022 to 07/18/2025. During the institutionalCOVID-19 Lab shutdown, we had to sac mice and stop the breeding; we restarted the knockouts and the generation and characterization of the new cre-flox inducible conditional knockouts.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2023
- Accession Number
- AD1227506
Entities
People
- Sylvain Doré
Organizations
- University of Florida