Allergic Neuritis: An Experimental Disease of Rabbits Induced by the Injection of Peripheral Nervous Tissue and Adjuvants

Abstract

In experimental allergic encephalomyelitis (EAE), produced by injecting rabbits with whole rabbit spinal cord together with tubercle bacilli and mineral oil, lesions comparable to those seen in the central nervous system are found in the nerve roots, spinal ganglia, and peripheral nerves. When special fractions of bovine white matter are used as antigen in rabbits, the same distribution of lesions is seen but peripheral nerve involvement is relatively less frequent. When rabbit sciatic nerve or spinal ganglia are used as antigen in rabbits, lesions occur only in the roots, ganglia, and peripheral nerves. Lesions are not produced in the central nervous system, nor is there a meningitis. This disease picture has been called experimental allergic neuritis (EAN). The antigenicity of rabbit nerve is not impaired by autoclaving. Sciatic nerve of other mammalian species produces the same disease in rabbits as does rabbit nerve. Optic nerve, used as antigen, produces the typical picture of EAE, not EAN. The optic nerves are not affected in EAN, whereas they commonly contain lesions in EAE. There are differences of symptomatology, referable to the difference in distribution of lesions, between EAE and EAN. The spinal fluid of EAE shows an increase both in the number of cells and in the total protein content. In EAN, the same changes in protein are observed, but usually the cell count remains normal. The cell count appears to be related to the involvement of cerebral and spinal meninges, which is an almost invariable accompaniment of EAE. The skin tests and serologic studies made with homologous and heterologous antigens were essentially non-contributory, apparently as a consequence of the diversity of antigens present in the inoculated materials. The similarity between EAN and certain of the human polyneuritides is indicated and discussed.

Demyelination and neurological signs in experimental allergic encephalomyelitis

“…Other workers have also reported demyelination in these models (Waksman and Adams 1955;Wisniewski et al 1969;Piliero and Cremonese 1973;McFarlin et al 1974;Dal Canto et al 1977). Electrophysiological studies have shown focal nerve conduction abnormalities in the DRGs and at the dorsal root entry zone in rabbits with EAE (Pender and Sears 1982, 1985, at the ventral root exit zones and in the DRGs of rats with whole-spinal-cordinduced EAE (Pender 1986a;Pender and Sears 1986) and in the sacrococcygeal dorsal roots of rats with MBP-induced EAE (Pender 1986b).…”

“…They concluded that these reports were invalid because of the nonspecificity of clinical signs, the occurrence of intercurrent diseases, the inadequacy or incorrect timing of histologic evaluations, and the lack of controls for specificity of the signs. The present paper emphasizes that, if clinicopathological correlations are to be made in EAE, one must thoroughly examine the PNS, which is known to be affected in EAE in all species studied (Freund et al 1947;Ferraro and Roizin 1954;Waksman andAdams 1955, 1956;Levine and Wenk 1963;Wisniewski et al 1969;Piliero and Cremonese 1973;McFarlin et al 1974;Dal Canto et al 1977), as well as the CNS, particularly the lumbar, sacral and coccygeal segments of the spinal cord. The involvement of the PNS when animals are inoculated with whole CNS tissue or purified CNS MBP is explained by the fact that the P1 MBP from the PNS is similar, if not identical to, CNS MBP (Brostoff and Eylar 1972;Greenfield et al 1973).…”

“…Demyelination of the PNS may account for the occurrence of neurological signs in the absence of CNS demyelination in guinea pigs with bovine MBP-induced EAE or encephalitogenic peptide-induced EAE (Hoffman et al 1973;Raine et al 1981) and in guinea pigs during the acute phase of chronic relapsing EAE (Lassmann and Wisniewski 1979). When assessing the PNS in guinea pigs with EAE, particular attention should be given to the peripheral nerves themselves, as well as to the spinal roots and ganglia, because the peripheral nerves are particularly affected in this species (Waksman and Adams 1956). It should be noted that CNS demyelination does occur in MBP-induced EAE in guinea pigs when guinea pig MBP or higher doses of bovine MBP are used (Lampert and Kies 1967;Colover 1980;Moore et al 1985).…”

Focal conduction block in the dorsal root ganglion in experimental allergic neuritis

“…The distribution of lesions in the PNS differs among different models of acute EAN. In rabbits and mice with acute EAN induced by inoculation with whole PNS tissue, the dorsal root ganglion is the most consistently affected region of the PNS [1,3]. The dorsal root ganglion is also a major site of involvement in rats with PNS myelin-induced or P2-induced acute EAN [4,5].…”

“…Experimental allergic neuritis (EAN) is an autoimmune demyelinating disease of the peripheral nervous system (PNS) induced by inoculation with PNS tissue [1] or P2 protein [2] and adjuvants. In its acute form, it is widely studied as an animal model of the human disorder, the Guillain-Barré syndrome.…”