i(3)so3-galactosylceramide and Encephalitis

Recent studies suggest that increased T-cell and autoantibody reactivity to lipids may be present in the autoimmune demyelinating disease multiple sclerosis. To perform large-scale multiplex analysis of antibody responses to lipids in multiple sclerosis, we developed microarrays composed of lipids present in the myelin sheath, including ganglioside, sulfatide, cerebroside, sphingomyelin and total brain lipid fractions. Lipid-array analysis showed lipid-specific antibodies against sulfatide, sphingomyelin and oxidized lipids in cerebrospinal fluid (CSF) derived from individuals with multiple sclerosis. Sulfatide-specific antibodies were also detected in SJL/J mice with acute experimental autoimmune encephalomyelitis (EAE). Immunization of mice with sulfatide plus myelin peptide resulted in a more severe disease course of EAE, and administration of sulfatide-specific antibody exacerbated EAE. Thus, autoimmune responses to sulfatide and other lipids are present in individuals with multiple sclerosis and in EAE, and may contribute to the pathogenesis of autoimmune demyelination.

Topics: Animals; Autoimmune Diseases; Brain; Disease Models, Animal; Encephalitis; Encephalomyelitis, Autoimmune, Experimental; Enzyme-Linked Immunosorbent Assay; Humans; Lipids; Mice; Microarray Analysis; Multiple Sclerosis; Reproducibility of Results; Sensitivity and Specificity; Sulfoglycosphingolipids; T-Lymphocytes

Liposomal encapsulation of radioiodinated anti-herpes nucleosides was undertaken to reduce metabolic inactivation and increase blood-brain barrier penetration of the nucleosides, and so provide formulations suitable for use in the non-invasive scintigraphic diagnosis of herpes simplex encephalitis (HSE). The nucleosides investigated were [125I]-IVdU and its more lipophilic 3-methyl derivative, and they were encapsulated in phosphatidylcholine:cholesterol:sulfatide liposomes with an efficiency of 4.4% and 1.7% respectively. The encapsulation of IVdU reduced in vitro phosphorolysis (by 31% in serum at 25 degrees C over 3 hr as compared with non-encapsulated IVdU), and markedly increased in vivo stability (fifty-fold greater than that of free drug). In normal mice, higher radioactivity levels were observed in most tissues and there was prolonged, constant blood and brain uptake. Biodistribution of liposomal IVdU in herpes simplex virus (HSV) infected animals was similar, but somewhat lower concentrations were attained. Liposomal encapsulation of [125I]-3-CH3-IVdU produced less dramatic changes in tissue distribution in either healthy or HSV infected mice, as compared with the non-encapsulated drug. Whilst, in HSV infected mice, liposomal encapsulation of both drugs caused increased uptake by spleen, liver and lung, the uptake by brain was still too low for detection by whole-body scintigraphy.

Topics: Animals; Blood-Brain Barrier; Cholesterol; Drug Stability; Encephalitis; Herpes Simplex; Idoxuridine; Iodine Radioisotopes; Liposomes; Male; Mice; Mice, Inbred Strains; Phosphatidylcholines; Simplexvirus; Sulfoglycosphingolipids; Temperature

Topics: Aged; Brain; Brain Chemistry; Cerebrosides; Child, Preschool; Chromatography, Thin Layer; Demyelinating Diseases; Diffuse Cerebral Sclerosis of Schilder; Encephalitis; Galactosidases; Gangliosides; Humans; Infant; Lipidoses; Lipids; Multiple Sclerosis; Sphingomyelins; Sulfatases; Sulfoglycosphingolipids

Topics: Cerebrosides; Diffuse Cerebral Sclerosis of Schilder; Encephalitis; Humans; Leukodystrophy, Metachromatic; Lipidoses; Plasma; Sulfoglycosphingolipids