Quantitative MRI analysis of the brain after twenty-two years of neuromyelitis optica indicates focal tissue damage.

BACKGROUND The long-term effect of neuromyelitis optica (NMO) on the brain is not well established. METHODS After 22 years of NMO, a patient's brain was examined by quantitative T1- and T2-weighted mono- and biexponential diffusion and proton spectroscopy. It was compared to 3 cases with short-term NMO and 20 healthy subjects. RESULTS Although routine T1- and T2-weighted images appeared to be normal, quantitative T1-, T2- and diffusion-weighted magnetic resonance imaging identified areas with high diffusivity and altered relaxation time in 'normal appearing white matter' (NAWM). In such abnormal NAWM regions, biexponential diffusion analysis and quantitative spectroscopy indicated extracellular edema and axonal loss, respectively. Repeated analysis 6 months later identified the same alterations. Such patchy alterations were not detectable in the NAWM of the 3 cases with short-term NMO, and they were also not quantitatively different from the controls. CONCLUSION After NMO of 22-year duration, metabolic changes, altered diffusivity and magnetic resonance relaxation features of patchy brain areas may suggest tissue damage in NAWM that persist for at least 6 months

Remodeling of Liver and Plasma Lipidomes in Mice Lacking Cyclophilin D

In recent years, several studies aimed to investigate the metabolic effects of non-functioning or absent cyclophilin D (CypD), a crucial regulatory component of mitochondrial permeability transition pores. It has been reported that the lack of CypD affects glucose and lipid metabolism. However, the findings are controversial regarding the metabolic pathways involved, and most reports describe the effect of a high-fat diet on metabolism. We performed a lipidomic analysis of plasma and liver samples of CypD-/- and wild-type (WT) mice to reveal the lipid-specific alterations resulting from the absence of CypD. In the CypD-/- mice compared to the WT animals, we found a significant change in 52% and 47% of the measured 225 and 201 lipid species in liver and plasma samples, respectively. The higher total lipid content detected in these tissues was not accompanied by abdominal fat accumulation assessed by nuclear magnetic resonance imaging. We also documented characteristic changes in the lipid composition of the liver and plasma as a result of CypD ablation with the relative increase in polyunsaturated membrane lipid species. In addition, we did not observe remarkable differences in the lipid distribution of hepatocytes using histochemistry, but we found characteristic changes in the hepatocyte ultrastructure in CypD-/- animals using electron microscopy. Our results highlight the possible long-term effects of CypD inhibition as a novel therapeutic consideration for various diseases