Biliverdin reductase, a major physiologic cytoprotectant, suppresses experimental autoimmune encephalomyelitis.

Oxidative stress plays an important role in the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Bilirubin is regarded today as a potent antioxidant. Recent studies show that the potent antioxidant actions of bilirubin reflect an amplification mechanism whereby biliverdin reductase (BVR) physiologically regenerates bilirubin in a catalytic cycle.

Treatment optimization in multiple sclerosis.

The treatment of multiple sclerosis has finally become possible with the advent of the current disease-modifying therapies (DMTs) that have had a significant impact on those living with this disease. Though demonstrating clear efficacy on a number of short-term outcome measures, unfortunately, these agents are not "cures" and many patients with multiple sclerosis continue to experience disease activity in spite of treatment. Clinicians are becoming more comfortable initiating therapy with DMTs, but it is now important to focus attention on monitoring the results of the chosen therapy and deciding whether or not a patient is responding well to treatment.

Longitudinal analyses of the effects of neutralizing antibodies on interferon beta-1b in relapsing-remitting multiple sclerosis.

We have analysed data on exacerbation rates, Expanded Disability Status Scale (EDSS) scores, and lesion burdens using the results of two neutralizing antibody (NAB) assays (CPE and MxA) from the pivotal relapsing-remitting multiple sclerosis (MS) trial of interferon beta-1b (IFNB) with a longitudinal approach, where the influence of NABs in individual patients is assessed by comparing responses during NAB-positive and NAB-negative periods. There are apparent influences on exacerbation rate related to dose of IFNB, titer level, and duration of positivity. With the MxA assay, exacerbation rates after switching to NAB-positive status are estimated to be 28% higher [95% confidence interval (CI): (-15%, 92%)] and -2% higher [95% CI: (-21%, 21%)] on the low- and high-dose IFNB arms, respectively.

Clinical relapses of multiple sclerosis are associated with 'novel' valleys in natural killer cell functional activity.

Natural killer (NK) cells are implicated in the pathogenesis of multiple sclerosis (MS). Nine relapsing-remitting MS (RRMS) patients along with age, sex, and NK responder status matched controls were studied serially. Although the average NK cell functional activity (FA) was not significantly different between both groups, four clinical relapses in RRMS patients were associated with the development of 'novel' valleys in FA.

Evolution of focal and diffuse magnetisation transfer abnormalities in multiple sclerosis.

Magnetisation transfer (MT) imaging provides indirect information on tissue structure abnormalities in areas that otherwise may appear normal on conventional MRI. We determined the evolution of MT changes in normal appearing white matter (NAWM) and lesion on serial examination of 9 multiple sclerosis (MS) patients and age matched controls. The mean NAWM MT ratio (MTR) was found to correlate strongly (R = 0.

Bilirubin as a potent antioxidant suppresses experimental autoimmune encephalomyelitis: implications for the role of oxidative stress in the development of multiple sclerosis.

Increasing evidence shows that oxidative stress plays an important role in the pathogenesis of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). In recent years, bilirubin has been demonstrated to be a potent antioxidant in vitro. In this study, we administered bilirubin to rats with acute and chronic EAE.

Dendritic and synaptic pathology in experimental autoimmune encephalomyelitis.

Evidence has shown that excitotoxicity may contribute to the loss of central nervous system axons and oligodendrocytes in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Because dendrites and synapses are vulnerable to excitotoxicity, we examined these structures in acute and chronic models of EAE. Immunostaining for microtubule-associated protein-2 showed that extensive dendritic beading occurred in the white matter of the lumbosacral spinal cord (LSSC) during acute EAE episodes and EAE relapses.

Intrathecal Fas ligand infusion strengthens immunoprivilege of central nervous system and suppresses experimental autoimmune encephalomyelitis.

Fas ligand (FasL) is an essential molecule strongly expressed in some immunoprivileged sites, but is expressed at very low levels in normal CNS. In this study, acute experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats with guinea pig myelin basic protein. Intrathecal infusion of recombinant FasL before EAE onset dose dependently suppressed acute EAE and alleviated pathological inflammation in lumbosacral spinal cord.

Normal-appearing white matter in multiple sclerosis has heterogeneous, diffusely prolonged T(2).

T(2) relaxation in normal-appearing white matter (NAWM) of multiple sclerosis (MS) patients was reexamined using more complete sampling and analysis of decay curves, and to assess focal vs. diffuse abnormalities. Nine MS patients and 10 controls were scanned using a single-slice 32-echo pulse sequence with a 10-ms echo spacing.