In addition, we chose to explore the protective effect of inhibiting the Toll-like receptor 4 (TLR4) pathway for two reasons: (i) TLR4 is an inducer of RIPK1-independent necroptosis (23) and (ii) hyperammonemia has been reported to activate TLR4 and to induce TLR4 up-regulation in brain endothelial cells (24). Here, TLR4 is linked to Hyperammonemia.