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Neuroprotective Mechanism of DMF/MMF Associated With CAA-Related Pathology After TBI
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 anti-oxidative 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 the veterans and active military people. However, it is unclear whether DMF has superior beneficial effects over MMF or vice versa. Furthermore, whether the therapeutic window would differ from acute TBI over repetitive concussion-like brain insults leading to CAA needs to be tested. Considering these knowledge gaps, we aim to start answering these questions using preclinical models. For this past year, we successfully maintained/renewed the animal protocols approved by the Institutional IACUC. During the institutional COVID-19 Lab shutdown, we had to sac mice and stopped breeding; we have recently restarted breeding for the knockouts as well as the generation and characterization of the new cre-lox inducible conditional knockouts.
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