Allergic demyelination

Aluminium overload Allergic encephalomyelitis (demyelinating diseases) Ageing... 

Raine, C. S., Wisniewski, H. and Prineas, J. An ultrastruc-tural study of experimental demyelination and remyelin-ation. II. Chronic experimental allergic encephalomyelitis in the peripheral nervous system. Lab. Invest. 21 316-327, 1969. 

Experimental allergic encephalomyelitis is an animal model of autoimmune demyelination 640... 

Most cells of the immune system are ordinarily kept apart from those of the nervous system by means of the blood-brain barrier. However, allergic encephalomyelitis, in which T cells attack the myelin sheath of brain neurons, can easily be induced in mice.506 A similar autoimmune process is thought to be involved in human multiple sclerosis (see Chapter 30, pp. 1769, 1808, and Fig. 30-9).507,508 High levels of circulating IgM are found in some demyelinating diseases of peripheral neurons.508 In Rasmussen s encephalitis, which causes brain inflammation and epilepsy, serum antibodies attack a glutamate receptor subunit GluR3.509... 

EAE experimental allergic/autoimmune encephalitis is an animal model for demyelinating diseases, such as multiple sclerosis. It is induced by injection of myelin basic protein or whole CNS tissue together with adjuvants. 

Linington C, Bradl M, Lassmann H, Brunner C, Vass K (1988) Augmentation of demyelination in rat acute allergic encephalomyelitis by circulating mouse monoclonal antibodies directed against a myelin/oligodendrocyte glycoprotein. Am J Pathol 130 443 54. 

Serial MRI documents that clinical MS exacerbations are associated with focal BBB damage. As early as 1965, experimental allergic/autoimmune encephomyelitis (EAE) animal models revealed lymphocyte adherence to post capillary venules and subsequent migration into CNS parenchyma preceding demyelination (Lampert and Carpenter, 1965). Both... 

Lampert P, Carpenter S (1965) Electron microscope studies on the vascular permeability and the mechanisms of demyelination in experimental allergic encephalomyelitis. J Neuropathol Exp Neurol 29 11-24. 

Multiple sclerosis (MS) has traditionally been viewed as a disorder in which myelin is the primary target. However, there is recent evidence for abnormal SNS expression in experimental models of demyelination and in MS. Black et al (1999b) studied Na channel expression in the taiep rat, a mutant model in which myelin is initially formed normally, but then lost as a result of an oligodendrocyte abnormality. They observed the abnormal expression of SNS Na channel mRNA and protein in Purkinje cells following loss of myelin. More recently. Black et al (2000) demonstrated that SNS mRNA and protein, which are not detectable in normal Purkinje cells, are expressed within Purkinje cells in a mouse model of MS, chronic relapsing experimental allergic encephalomyelitis. Black et al (2000) have also demonstrated the expression of SNS mRNA (Fig. 7a, b) and protein (Fig. 7e, f) within cerebellar Purkinje cells from tissue obtained post-mortem from MS patients, but not in controls with no neurological disease (Fig. 7c, g). 

Experimental allergic encephalomyelitis (EAE). Autoimmune demyelinating disease induced in genetically susceptible mice, rats, or marmosets by immunization with myelin proteins or peptides. Animal model for multiple sclerosis. 

Riskind PN, Massacesi L, Doolittle TH, Hauser SL (1991) The role of prolactin in autoimmune demyelination suppression of experimental allergic encephalomyelitis by bromocriptine. Ann Neurol, 29(5) 542-547. 

In experiments on an animal model of experimental allergic neuritis, a demyelinating disease, treatment with Org 2766 protected the myelinated nerve fibers of the sural nerve from degeneration (Duckers et al., 1994), an action similar to that observed for lesions of the substantia nigra (see Section 6) and for sensory and glial cells in culture (see Section 7). 

Duckers, H.J., Verhaagen J., de Bruijn, E. and Gispen, W.H. (1994). Effective use of a neurotrophic ACTH 4-9 analog in the treatment of a peripheral demyelinating syndrome (experimental allergic neuritis). An intervention study. Brain 117 365-374. 

The MBPS are a family of proteins. Unlike PLP, MBPs are easily extracted from the membrane and are soluble in aqueous solution. The major MBP has no tertiary structure and has a molecular weight of 15,000 Daltons. MBP is located on the cytoplasmic face of myelin membranes. Antibodies directed against MBPs elicit experimental allergic encephalomyelitis (EAE), which has become a model system for understanding multiple sclerosis, a demyelinating disease. A model of how PLP and MBPs aid in stabilizing myelin is shown in Figure 48.14. 

Although the current protein-based TNF inhibitors have demonstrated ligand-inhibitory efficacy, they can also exhibit potentially serious adverse efiects such as a greater predisposition towards secondary infections, congestive heart failure, neurologic changes (demyelination), lymphomas, re-exacerbation of latent tuberculosis and problems related to autoimmunity such as lupus-like syndrome. With infliximab, acute allergic reactions are seen in approximately 5% of intravenous infusions as well. 

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