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

Abstract

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.