Neuroinflammation and demyelination from the point of nitrosative stress as a new target for neuroprotection

Abstract

<jats:title>Abstract</jats:title><jats:p>The role of nitrosative stress in the early pathogenesis of neuroinflammation and demyelination is undoubtedly wide. This review summarizes and integrates the results, found in previously performed studies, which have evaluated nitrosative stress participation in neuroinflammation. The largest number of studies indicates that the supply of nitrosative stress inhibitors has led to the opposite clinical effects in experimental studies. Some results claim that attributing the protective role to nitric oxide, outside the total changes of redox oxidative processes and without following the clinical and paraclinical correlates of neuroinflammation, is an overrated role of this mediator. The fact is that the use of nitrosative stress inhibitors would be justified in the earlier phases of neuroinflammation. The ideal choice would be a specific inducible nitric oxide synthase (iNOS) inhibitor, because its use would preserve the physiological features of nitric oxide produced by the effects of constitutive NOS. This review discusses the antinitrosative therapy as a potential mode of therapy that aims to control neuroinflammation in early phases, delaying its later phases, which are accompanied with irreversible neurological disabilities. Some parameters of nitrosative stress might serve as surrogate biomarkers for neuroinflammation intensity and its radiological and clinical correlates.</jats:p>

Delayed Influence of Spinal Cord Injury on the Amino Acids of NO• Metabolism in Rat Cerebral Cortex Is Attenuated by Thiamine

“…SCIs are known to result in chronic inflammatory response in cerebral cortex, leading to neurodegeneration and functional impairment ( 15 , 18 ), but the molecular mechanisms of such perturbations remain to be unraveled. The role of NO • signaling in the short-term progression of acute inflammation was extensively studied, with enhanced NO • synthesis having both positive and negative effects during inflammatory process ( 46 ). To understand potential contribution of the NO • -related pathways into the sequelae of SCI in areas of nervous system distant from the damage site, we performed quantification of the brain amino acids involved in NO • metabolism (Figure 1 ).…”

Physiological Levels of Nitric Oxide Diminish Mitochondrial Superoxide. Potential Role of Mitochondrial Dinitrosyl Iron Complexes and Nitrosothiols

“…It is conceivable that decreased NO level in cardiovascular conditions (Landmesser and Harrison, 2001 ) may contribute to mitochondrial dysfunction and strategies to improve NO-production by eNOS such as tetrahydrobiopterin supplementation can also improve mitochondrial function. On the other hand, a number of pathological conditions dealing with hepatotoxicity and neurodegeneration are associated with NO • overproduction by iNOS as well as with the increased oxidative stress (Venkatraman et al, 2004 ) and, therefore, specific inhibition of iNOS can be beneficial (Ljubisavljevic and Stojanovic, 2015 ). It is possible that effect of nitric oxide on mitochondrial functions has a bell shaped curve and, therefore, require an optimal NO level to balance the oxidative stress and metabolic activity.…”

Low-Dose Ribavirin Treatments Attenuate Neuroinflammatory Activation of BV-2 Cells by Interfering with Inducible Nitric Oxide Synthase

“…Given the fact that overproduction of NO by activated microglia during the neuroinflammation leads to the development of reactive nitrogen species, such as peroxynitrite, nitrogen dioxide, which exert devastating effects on the neuronal cells (reviewed in [ 32 ]), obtained results strongly suggest that low-dose RBV treatment may be neuroprotective, due to low toxicity and high efficiency in NO suppression. Attenuation of nitrosative stress through the modulation of iNOS could be beneficial if applied early in neuroinflammatory states associated with demyelinating diseases [ 44 , 45 ], such as multiple sclerosis.…”