Rabies is a lethal disease caused by a neurotropic virus that produces inconspicuous morphological changes hardly observable with conventional histopathology.The fatal outcome caused by rabies could be attributed to specific biochemical changes that severely impact neuronal function.The neuronal nuclear protein (NeuN) has become a widely used neuronal marker for the research and the histopathological diagnosis of nervous system diseases.To evaluate the distribution of the protein NeuN in the motor cortex of normal and rabies-infected mice adult ICR mice were inoculated with rabies virus either intramuscularly or intracerebrally.Rabies-infected mice were sacrificed at the terminal stage of the disease.Control mice were also euthanized at the same age.The brains were removed and cut into coronal sections on a vibratome.Immunohistochemistry was used to study the expression of NeuN in the motor area of the cerebral cortex.Neuronal counts, cellular optical densitometry and neuronal diameter measurements were performed to analyze the immunoreactivity of the protein.All parameters revealed decreased immunoreactivity for NeuN in cortical neurons of mice intracerebrally infected with rabies.In contrast, the changes were not statistically significant in mice inoculated intramuscularly.Either the immunoreactivity of NeuN or its expression is affected by the presence of rabies virus in the cerebral cortex depending on the inoculation route.These results contribute to the knowledge of the dynamics of cellular infection on rabies pathogenesis.