Lewis rat EAN is suppressed by the 21-aminosteroid tirilazad mesylate (U-74006F).

Lewis rat experimental allergic neuritis (EAN) was treated with the 21-aminosteroid, tirilazad mesylate (U-74006F). High doses of tirilazad mesylate, begun just before the onset of clinical signs, reduced the clinical and pathological severity of the disease. In rats immunized with a high dose of myelin, axonal degeneration was a major pathological feature. Tirilazad mesylate reduced the amount of axonal degeneration but had little effect on the other pathological features of EAN, such as inflammation and demyelination. Tirilazad mesylate may block axonal degeneration by inhibiting lipid peroxidation of axonal membranes. Inhibition of axonal degeneration is an important goal in the treatment of human neuropathies.

Antigalactocerebroside antibody increases demyelination in adoptive transfer experimental allergic neuritis.

There is suggestive but inconclusive evidence for a contribution of T cells and antimyelin antibodies to the pathogenesis of the Guillain-Barré polyneuropathy. We have studied the potential synergism of cellular and humoral immunity in the adoptive transfer model of EAN. EAN was induced in Lewis rats by injecting varying doses of P2 peptide (SP26)-sensitized T lymphocytes. Disease severity was dose-dependent. The addition of intravenous GC-AB to a subclinical dose of SP26-sensitized T cells resulted in overt clinical disease and markedly enhanced demyelination. Intravenous injection of antibody alone had no effect. We conclude that activated neuritogenic T cells, while entering into peripheral nerves, alter the blood-nerve barrier, which gives circulating demyelinating antibodies access to the endoneurium. The observations support the concept of a synergistic role of T-cell autoimmunity and humoral responses in the inflammatory demyelination of Lewis rat EAN.

Adoptive transfer of experimental allergic neuritis in the immune suppressed host.

Experimental allergic neuritis (EAN) was induced in normal and irradiated Lewis rats by passively transferring T cells sensitized to SP-26, a peptide fragment of P2 myelin protein. The recipients became sick 4-8 days post transfer and the degree of disability correlated directly with the dose of T cells. Smaller doses caused demyelination of nerve roots and sciatic nerves and larger doses produced more severe demyelination and significant axonal degeneration. Irradiated recipients developed similar clinical EAN and showed macrophage-mediated demyelination despite severe suppression of the host inflammatory response.

P2-peptide induced experimental allergic neuritis: a model to study axonal degeneration.

In experimental allergic neuritis (EAN) severity of clinical disease and pathology correlate with the dose of antigen (Hahn et al., Lab Invest 59:115-125, 1988). To avoid axonal membrane contamination of the antigen, EAN was induced with a synthetic peptide, corresponding to residues 53-78 of bovine P2 myelin protein. Severity of EAN correlated with the dose of peptide in the inoculate. The relationship between demyelination, inflammation and axonal degeneration was studied. Low doses resulted in pure demyelination. Axonal degeneration occurred only with high doses of antigen and in association with very active mononuclear inflammation. The role of macrophages in producing axonal damage is discussed.

Demyelination and axonal degeneration in Lewis rat experimental allergic neuritis depend on the myelin dosage.

We describe the clinical and pathologic features of experimental allergic neuritis in Lewis rats inoculated with varying doses of myelin, ranging from 0.5 to 20 mg. The clinical scores were assessed daily. On days 18 and 19 or 28 postimmunization, the rats were perfused with fixative and samples of cervical and lumbar roots and sciatic nerves were processed and embedded in Epon. Tissues were examined by light and electron microscopy and the degree of edema, inflammation, demyelination, and axonal degeneration was assessed quantitatively. We found that the severity of clinical and pathologic experimental allergic neuritis correlated positively with the dose of myelin used for immunization. High dose tolerance was not observed. Demyelination prevailed in nerve roots and increased with higher doses of antigen. Accompanying axonal degeneration was seen only with high doses of myelin. The pathology of sciatic nerves differed. Sciatic nerves of rats immunized with 0.5 and 1 mg of myelin were either normal or showed perivenular lymphocytic infiltrates and demyelination, but nerves from rats with higher immunizing doses of myelin showed increasingly severe axonal degeneration. The axonal degeneration in nerve roots paralleled the degree of inflammation and demyelination and may have been a nonspecific product of the inflammatory reaction. However, the much more severe axonal destruction seen in sciatic nerves with high myelin doses was probably due to other pathogenetic mechanisms.

Treatment of experimental allergic neuritis with prednisolone.

Experimental allergic neuritis (EAN) in Lewis rats was treated with prednisolone given prophylactically or therapeutically. Rats treated from the time of immunization with myelin or after the establishment of clinical disease improved more rapidly than controls. Treatment at the onset of clinical signs resulted in less severe disease and more rapid recovery. Rats treated just prior to the onset of clinical signs (day 10) did not develop significant clinical disease and appeared to have less inflammation in their nerves and nerve roots on microscopic examination.