Endocannabinoid Metabolism and Traumatic Brain Injury

Zhu, Gao, Chen, Dexiao Zhu, Fei Gao, Chu Chen

The inflammatory response is one of the major features of brain damage in the case of secondary injury. The anti-inflammatory effects of LXs and ATLs in TBI appear to be via binding to FPR2 to suppress cytokines, including IL1β, IL6, and TNF, in mice [ 49 ]. Increased tau phosphorylation has been demonstrated in models of mild and severe TBI [ 58 ]. A previous study demonstrated that pharmacological inhibition of MAGL reduced the levels of phosphorylated tau as well as of P25 and phosphorylated GSK3β, key players in tau phosphorylation, 8 and 30 days after the first injury in a mouse model of repetitive mild closed-head injury [ 40 ], suggesting that inhibition of 2-AG metabolism is capable of suppressing tau phosphorylation. Importantly, this study revealed that pharmacological inactivation of MAGL robustly reduced TDP-43 production, providing the first evidence that inhibition of 2-AG metabolism prevents TBI-induced excessive formation of TDP-43, which, in turn, promotes recovery from the secondary injury, thus preventing cognitive decline [ 40 ].

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