Nitric Oxide Metabolites And InterLeukin-6 In CerebroSpinal Fluid From Multiple Sclerosis
Miljkovic Dj, Drulovic J, Trajkovic V, Mesaros S, Dujmovic I, Maksimovic D, Samardzic T, Stojsavljevic N, Levic Z, Mostarica Stojkovic M
Eur J Neurol 2002 Jul;9(4):413-8
Institute for Biological Research Sinisa Stankovic, Belgrade, Yugoslavia
PMID# 12099927; UI# 22095208
InterLeukin-6 (IL-6) and Nitric Oxide (NO) are implicated in the pathology of Multiple Sclerosis (MS). We have investigated the levels of these mediators in the CerebroSpinal Fluid (CSF) from 50 patients with MS and 23 control subjects.
Mean CSF IL-6 level was higher in the total MS group in comparison with controls, but not significantly, whilst the difference between patients with stable MS and controls reached the level of statistical significance.
Mean CSF Nitrite/Nitrate level was significantly higher in the total MS group compared with the control group, as well as in active MS patients versus controls.
There was significant difference neither in the mean CSF IL-6 nor in Nitrite/Nitrate levels between active and stable MS patients.
Interestingly, we observed a significant negative correlation between IL-6 and Nitrite/Nitrate levels in the CSF in the total MS group.
Such a trend existed in both subgroups with active and stable MS, but without reaching the level of statistical significance.
Our data further support the involvement of IL-6 and NO in ongoing pathological processes in MS, suggesting their potential interplay within the Central Nervous System in this disease.
Role Of Nitric Oxide In Inflammation-Mediated NeuroDegeneration
Liu B, Gao HM, Wang JY, Jeohn GH, Cooper CL, Hong JS
Ann N Y Acad Sci 2002 May;962:318-31
National Institutes of Health, National Institute of Environmental Health Sciences, NeuropPharmacology Section, Laboratory of Pharmacology and Chemistry, Research Triangle Park, North Carolina 27710, USA
PMID# 12076984; UI# 22071475
Increasing evidence has suggested that inflammation in the Brain is closely associated with the pathogenesis of several Degenerative Neurologic Disorders, including Parkinson's Disease, Alzheimer's Diseases, Multiple Sclerosis, Amyotrophic Lateral Sclerosis, and AIDS Dementia.
The hallmark of Brain inflammation is the activation of Glial Cells, especially that of Microglia that produce a variety of ProInflammatory and NeuroToxic factors, including Cytokines, Fatty Acid Metabolites, Free Radicals - such as Nitric Oxide (NO) and SuperOxide.
Excessive production of NO, as a consequence of Nitric Oxide Synthase induction in activated Glia, has been attributed to participate in NeuroDegeneration.
Using primary mixed Neuron-Glia cultures and Glia-enriched cultures prepared from embryonic rodent Brain tissues, we have systemically studied the relationship between the production of NO and NeuroDegeneration in response to stimulation by the inflammagen LipopolySaccharide.
This review summarizes our recent findings on the kinetics of NO generation:
- The relative contribution of Microglia and Astrocytes to NO accumulation
- The relationship between NO production and NeuroDegeneration
- Points of intervention along the pathways associated with NO generation to achieve NeuroProtection
We also describe our results relating to the effect of several Opioid-related agents on Microglial activation and NeuroProtection.
Among these agents, the Opioid Receptor Antagonist Naloxone, especially its NonOpioid Enantiomer +-Naloxone, promises to be of potential therapeutic value for the treatment of Inflammation-Related Diseases.
CSF Nitric Oxide Metabolites Are Associated With Activity And Progression Of Multiple Sclerosis
Rejdak K, Eikelenboom MJ, Petzold A, Thompson EJ, Stelmasiak Z, Lazeron RH, Barkhof F, Polman CH, Uitdehaag BM, Giovannoni G
Neurology 2004 Oct 26;63(8):1439-45
Institute of Neurology, Department of NeuroInflammation, London, UK
To investigate the relationship of CSF and the Serum Nitric Oxide metabolites Nitrite and Nitrate (NOx) to disease activity and progression in patients with Multiple Sclerosis (MS).
The study was divided into cross-sectional and follow-up. In the cross-sectional study, 20 patients with Relapsing/Remitting (RR), 21 with Secondary/Progressive (SP), and 10 with Primary/Progressive (PP) MS and 14 control subjects were included.
Patients were assessed on clinical (Expanded Disability Status Scale [EDSS], Ambulation Index [AI], 9-Hole Peg Test [9-HPT]) and MRI measurements.
In the follow-up study, 34 MS patients from the cross-sectional study agreed to be assessed again after an average of 3.0 +/- 0.5 years. NOx was measured using a vanadium-based assay.
In the cross-sectional study, CSF NOx was raised in patients with RR-MS (p = 0.001) and PP-MS (p = 0.02) vs controls.
Higher CSF NOx levels were found in patients with mild disability (AI < or = 6.0; EDSS < or = 4.0; Multiple Sclerosis Severity Score [MSSS] < or = 4.8) vs patients with advanced disease (AI > 6.0 [p = 0.002]; EDSS > 4.0 [p = 0.02]; MSSS > 4.8 [p = 0.01]).
In the subgroup of patients having Gd-enhancing MRI lesions (n = 11), correlation between the volume of enhancement and CSF NOx was found (r = 0.74, p = 0.01).
In the follow-up study, patients with disability progression had higher baseline CSF NOx levels than those who were stable on EDSS (p = 0.02) or AI (p = 0.03).
A positive correlation was found between baseline CSF NOx and the change in MR T2-weighted lesion load (r = 0.4, p = 0.03).
CSF Nitrite and Nitrate levels were increased in mildly disabled patients with MS and found to correlate with the volume of Gd-enhanced lesions on MRI.
Raised baseline CSF NOx was associated with clinical and MRI progression in MS patients over 3-year follow-up.