Mitochondrial dynamics and protective effects of a mitochondrial division inhibitor, Mdivi-1, in lipopolysaccharide-induced brain damage.

Sepsis is one of the most common reasons for mortality in Intensive Care Units. As a common but severe neurological complication, sepsis associated encephalopathy (SAE) has always been ignored and there is no generally accepted treatment. In this study, we demonstrated that Mdivi-1 ameliorated brain damage assessed by Nissl staining. Furthermore, Mdivi-1 reduced TUNEL-positive cells in hippocampus, and inhibited S100 calcium binding protein B (S100B) and neuron-specific enolase (NSE) release into plasma. Biochemical analysis also showed that Mdivi-1 protected hippocampus from oxidative stresses. Western blot analysis revealed that Mdivi-1, as a Drp1 inhibitor, inhibited LPS induced dynamin-related GTPase (Drp1) increase. Interestingly, it can also attenuate LPS induced optic atrophy 1 (OPA1) and phosphorylated Drp1 (p-Drp1) decrease. Thus Mdivi-1 protected rats from SAE, and this protective effect could be associated with its inhibition of Drp1 and its activation of p-Drp1 and OPA1. Mitochondrial dynamics may be a potential pharmacological therapeutic target for treating SAE.