Local autoimmune encephalomyelitis model in a rat brain with precise control over lesion placement.

Development of a novel, animal model for multiple sclerosis (MS) with reproducible and predictable lesion placement would enhance the discovery of effective treatments. Therefore, we would like to combine the advantages of the demyelination model with experimental autoimmune encephalomyelitis (EAE) to provide a local autoimmune encephalomyelitis (LAE) inside rat brain. We induced a demyelinating lesion by immunizing male Wistar rats, followed by blood-brain barrier opening protein (vascular endothelial growth factor) by stereotactic injection. We confirmed the immunization against myelin epitopes and minor neurological impairment. Histological assessment confirmed the lesion development after both 3- and 7 days post-injection. Our approach was sufficient to develop a demyelinating lesion with high reproducibility and low morbidity.

Effect of Lipopolysaccharide-Induced Inflammatory Challenge on ß-Glucuronidase Activity and the Concentration of Quercetin and Its Metabolites in the Choroid Plexus, Blood Plasma and Cerebrospinal Fluid.

Quercetin-3-glucuronide (Q3GA), the main phase II metabolite of quercetin (Q) in human plasma, is considered to be a more stable form of Q for transport with the bloodstream to tissues, where it can be potentially deconjugated by ß-glucuronidase (ß-Gluc) to Q aglycone, which easily enters the brain. This study evaluates the effect of lipopolysaccharide (LPS)-induced acute inflammation on ß-Gluc gene expression in the choroid plexus (ChP) and its activity in blood plasma, ChP and cerebrospinal fluid (CSF), and the concentration of Q and its phase II metabolites in blood plasma and CSF. Studies were performed on saline- and LPS-treated adult ewes (n = 40) receiving Q3GA intravenously (n = 16) and on primary rat ChP epithelial cells and human ChP epithelial papilloma cells. We observed that acute inflammation stimulated ß-Gluc activity in the ChP and blood plasma, but not in ChP epithelial cells and CSF, and did not affect Q and its phase II metabolite concentrations in plasma and CSF, except Q3GA, for which the plasma concentration was higher 30 min after administration (p < 0.05) in LPS- compared to saline-treated ewes. The lack of Q3GA deconjugation in the ChP observed under physiological and acute inflammatory conditions, however, does not exclude its possible role in the course of neurodegenerative diseases.