Intracranial Inoculation Is More Potent Than Intranasal Inoculation for Inducing Optic Neuritis in the Mouse Hepatitis Virus-Induced Model of Multiple Sclerosis

Singh, Manmeet; Khan, Reas S.; Dine, Kimberly; Das Sarma, Jayasri; Shindler, Kenneth S.

The current studies compared effects of RSA59 infection via two different routes of inoculation on the development of demyelinating disease in the optic nerve and spinal cord. Results suggest intracranial inoculation is the best method to induce neuroinflammation. In the current study, intracranial infection of RSA59 lead to chronic stage inflammation and demyelination in both the optic nerve and spinal cord. This result is consistent with earlier studies where intracranial inoculation of RSA59 or its parental strain MHV-A59 led to demyelination and axonal loss in spinal cord ) and optic nerve (Shindler et al., 2008 (Shindler et al., , 2011 . Induction of optic neuritis by intracranial inoculation of RSA59 is dependent on retrograde transport of viral antigen along RGC axons that occurs over several days and results in late stage demyelination (Shindler et al., 2011) as seen again in the current study. Together, spinal cord and optic nerve pathology observed after intracranial inoculation of RSA59 in the current study confirm that the viral titer used retains its previously identified ability to induce CNS demyelinating disease.