Multiple sclerosis is an immune-mediated disorder of the central nervous
system leading to progressive decline of motor and sensory functions and permanent
disability1,
2. The therapy of multiple sclerosis is only partially
effective, despite anti-inflammatory, immunosuppresive and immunomodulatory
measures3. White matter inflammation and loss of myelin, the
pathological hallmarks of multiple sclerosis, are thought to determine disease
severity4,
5. Experimental autoimmune encephalomyelitis reproduces
the features of multiple sclerosis in rodents and in nonhuman primates6,
7. The dominant early clinical symptom of acute autoimmune encephalomyelitis
is progressive ascending muscle weakness6. However, demyelination
may not be profound and its extent may not correlate with severity of neurological
decline8, indicating that targets unrelated to myelin or oligodendrocytes
may contribute to the pathogenesis of acute autoimmune encephalomyelitis.
Here we report that within the spinal cord in the course of autoimmune encephalomyelitis
not only myelin but also neurons are subject to lymphocyte attack and may
degenerate. Blockade of glutamate AMPA receptors ameliorated the neurological
sequelae of autoimmune encephalomyelitis, indicating the potential for AMPA
antagonists in the therapy of multiple sclerosis.
