Nitric oxide localized to spinal cords of mice with experimental allergic encephalomyelitis: an electron paramagnetic resonance study.

Abstract

SummaryExperimental allergic encephalomyelitis (EAE) is a demyelinating autoimmune disorder that can be induced in susceptible mice by T lymphocytes sensitized to central nervous system (CNS) myelin components and is a prime animal model for the human CNS demyelinating disorder, multiple sclerosis (MS). Although CNS inflammation in which T lymphocytes and activated macrophages are the predominant cell types is observed in mice with EAE and in humans with MS, the exact mechanisms underlying the CNS damage and demyelination are not understood. Nitric oxide (NO), a gaseous free radical, has recently been shown to be a cytolytic product of activated macrophages. Using electron paramagnetic resonance spectroscopy, the nitric oxide free radical complexed with iron-sulfur proteins has been identified in affected spinal cords of mice with EAE, concurrent with the diminution of iron-sulfur proteins. These results indicate NO may play a role in the disease process of EAE, and perhaps MS.

Antioxidants and polyunsaturated fatty acids in multiple sclerosis

“…Antioxidant treatment in experimental models of MS Activated macrophages and microglia may produce high levels of NO and H 2 O 2 that are involved in the pathogenesis of EAE (Lin et al, 1993;Ruuls et al, 1995;Minghetti & Levi, 1998). Treatment of EAE with catalase, a H 2 O 2 scavenger, markedly suppressed disease severity (Ruuls et al, 1995).…”

“…Reactive oxygen species (ROS) are implicated as mediators of demyelination and axonal damage in both MS and experimental allergic encephalomyelitis (EAE) (Lin et al, 1993;Cross et al, 1997;van der Goes et al, 1998), an animal model of MS. Local ROS levels increase dramatically under inflammatory conditions and exhaust the antioxidant defence potential within the lesions (Smith et al, 1999). These excessive ROS levels are primarily generated by activated macrophages and microglia (Fisher et al, 1988;Hartung et al, 1992).…”

The Central Nervous System Inflammatory Response to Neurotropic Virus Infection Is Peroxynitrite Dependent

“…For instance, administration of uric acid (UA), a natural inhibitor of select chemical reactions associated with ONOO Ϫ , to animals with EAE protects the blood-CNS barrier from permeability changes normally associated with the disease (30). As the production of the ONOO Ϫ precursor NO • is a hallmark of the CNS inflammatory response in both EAE (15,22) and acute Borna disease (15), we postulate that ONOO Ϫ may have a physiological role in neuroimmune responses to enhance BBB permeability and promote cell invasion into the CNS. To investigate whether this may be the case for a neurotropic virus infection, we have assessed the effects of UA treatment on BBB permeability, CNS inflammation, and clinical disease in immunocompetent adult rats acutely infected with BDV.…”

“…Studies of experimental allergic encephalomyelitis (EAE) have provided considerable information concerning CNS inflammatory disease in the absence of an underlying viral infection. In this model, acute neurological disease is triggered by sensitization of CD4 T cells with myelin Ags, and CNS pathology has been associated with free radical production by inflammatory cells (21)(22)(23). Peroxynitrite (ONOO Ϫ ), the product of NO ⅐ and O 2 ⅐Ϫ , is believed to be an important toxic molecule in this context (24 -27).…”

Expression of the gene for inducible nitric oxide synthase in experimental glomerulonephritis in the rat

“…The presence of iNOS mRNA has been shown in experimental neurological inflammation [12], in the pancreas in experimental diabetes mellitus [ 13] and in experimental arthritis [14]. The production of NO itself in vivo has been shown by the use of electron paramagnetic resonance spectroscopy in allograft rejection [15], septic shock [16] and in experimental allergic encephalomyelitis [17].…”