TNF-α and IL-10 downregulation and marked oxidative stress in Neuromyelitis Optica

<p>Abstract</p> <p>Background</p> <p>Neuromyelitis optica is a central nervous system demyelinating and inflammatory syndrome. The objective of this study is to identify cytokines related to the cellular immune response as well as blood brain barrier integrity and oxidative stress.</p> <p>Methods</p> <p>We performed a molecular characterization of cellular immune response and oxidative stress in serum from relapsing-NMO (R-NMO) patients and established the correlations between the clinical measurements and molecular parameters using the Bayesian approach.</p> <p>Serum samples from 11 patients with R-NMO diagnosed according to Wingerchuk criteria and matched in terms of age, gender and ethnicity with the healthy controls were analyzed. The levels of TNF-<it>α</it>, IFN-<it>γ</it>, IL-10, MMP-9, TIMP-1 and oxidative stress markers: malondialdehyde, advanced oxidation protein products, peroxidation potential, superoxide dismutase, catalase, and total hydroperoxides were measured.</p> <p>Results</p> <p>We found almost undetectable levels of TNF-<it>α</it>, a decreased production of IL-10 and a significant up-regulation of every oxidative stress biomarker studied. The insufficient production of TNF-<it>α </it>and IL-10 in R-NMO patients, which are two important players of T cell mediated immunoregulation, suggest an effector – regulator imbalance. The overproduction of oxygen reactive species as a consequence of the chronic inflammatory milieu is reflected on the excess of oxidative damage mediators detected. Furthermore, Multidimensional Scaling and a Bayesian linear regression model revealed a significant linear dependence between Expanded Disability Status Scale Kurtzke and TIMP-1; pointing to a possible predictive or prognostic value of this clinical-molecular relationship.</p> <p>Conclusion</p> <p>These results suggest that there is a breakdown in immunoregulatory mechanisms and noteworthy pro-oxidant environment contributing to NMO pathogenesis.</p

Clinical and electrophysiological characteristics of peripheral neuropathy in Cuban systemic lupus erythematosus patients

Background: Peripheral neuropathy (PN) is one of the most heterogeneous and poorly understood or characterized manifestations in systemic lupus erythematosus (SLE). The aim of this study was to describe the clinical and electrophysiological features, and neuropathic disease associations, in Cuban SLE patients. Patients and methods: One hundred and two consecutive SLE patients admitted to the Psychoneuroimmunology service at the National Institute of Nephrology were included in the study. Patients with other disorders known to cause neuropathy were excluded. Demographic, clinical and laboratory data were obtained using a pre-defined questionnaire. Nerve conduction studies were carried out in both upper and lower limbs. Neuropathy was defined as the presence of clinical symptoms and/or signs and bilateral abnormal nerve conduction study parameters. Results: The 102 patients were 99 females and 3 males with mean age of 46 ± 12 years and disease duration 8 ± 9 years. PN was found in 55/102 (53.9%) patients; 48 (87.3%) had clinical peripheral neuropathy manifestations and 7 (12.7%) were asymptomatic. Nerve conduction studies suggested asymmetric axonal-demyelination neuropathy pattern. Mixed sensory-motor neuropathy was the most common involvement in 23(41.8%) cases. The most frequent pattern was polyneuropathy. Compared to those without neuropathy, SLE-related polyneuropathy patients were significantly older, but had no other significant associations with demographic, disease duration or serological/immunological data. Conclusion: Peripheral nervous system manifestations are common in SLE; may be related to an increased susceptibility of peripheral nerves to effects of aging. Nerve conduction studies are recommended, therefore, for inclusion in the follow-up of SLE patients especially in the older population

Rotating and Neurochemical Activity of Rats Lesioned with Quinolinic Acid and Transplanted with Bone Marrow Mononuclear Cells

Huntington&rsquo;s disease (HD) is an inherited, neurodegenerative disorder that results from the degeneration of striatal neurons, mainly GABAergic neurons. The study of neurochemical activity has provided reliable markers to explain motor disorders. To treat neurodegenerative diseases, stem cell transplants with bone marrow (BM) have been performed for several decades. In this work we determine the effect of mononuclear bone marrow cell (mBMC) transplantation on the rotational behavior and neurochemical activity in a model of Huntington&rsquo;s disease in rats. Four experimental groups were organized: Group I: Control animals (n = 5); Group II: Lesion with quinolinic acid (QA) in the striatum (n = 5); Group III: Lesion with QA and transplant with mBMC (n = 5); Group IV: Lesion with QA and transplant with culture medium (Dulbecco&rsquo;s modified Eagle&rsquo;s medium (DMEM) injection) (n = 5). The rotational activity induced by D-amphetamine was evaluated and the concentration of the neurotransmitter amino acids (glutamate and GABA) was studied. The striatal cell transplantation decreases the rotations induced by D-amphetamine (p &lt; 0.04, Wilcoxon matched pairs test) and improves the changes produced in the levels of neurotransmitters studied. This work suggests that the loss of GABAergic neurons in the brain of rats lesioned with AQ produces behavioral and neurochemical alterations that can be reversed with the use of bone marrow mononuclear cell transplants

Follow-Up of Peripheral IL-1β and IL-6 and Relation with Apoptotic Death in Drug-Resistant Temporal Lobe Epilepsy Patients Submitted to Surgery

Increasing amounts of evidence support the role of inflammation in epilepsy. This study was done to evaluate serum follow-up of IL-1β and IL-6 levels, as well as their concentration in the neocortex, and the relationship of central inflammation with NF-κB and annexin V in drug-resistant temporal lobe epileptic (DRTLE) patients submitted to surgical treatment. Peripheral and central levels of IL-1β and IL-6were measured by ELISA in 10 DRTLE patients. The sera from patients were taken before surgery, and 12 and 24 months after surgical treatment. The neocortical expression of NF-κB was evaluated by western blotting and annexin V co-localization with synaptophysin by immunohistochemistry. The neocortical tissues from five patients who died by non-neurological causes were used as control. Decreased serum levels of IL-1 and IL-6 were observed after surgery; at this time, 70% of patients were seizure-free. No values of IL-1 and IL-6 were detected in neocortical control tissue, whereas cytokine levels were evidenced in DRTLE. Increased NF-κB neocortex expression was found and the positive annexin V neurons were more obvious in the DRTLE tissue, correlating with IL-6 levels. The follow-up study confirmed that the inflammatory alterations disappeared one year after surgery, when the majority of patients were seizure-free, and the apoptotic death process correlated with inflammation