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.

Following intranasal inoculation of mice, MHV accesses the CNS through the olfactory nerve and spreads from the olfactory system (Jacobsen and Perlman, 1990; Perlman et al., 1990) into structures of the limbic system and their brainstem connections. This has led investigators to suggest that interneuronal transport is one mechanism of viral spread during acute encephalitis (Barthold, 1988; Lavi et al., 1988; , and studies showing spread of virus sequentially from cerebral hemispheres to brainstem to spinal cord provide further support for this interneuronal transport mechanism. Similar axonal transport of virus from brain to spinal cord (Das Sarma et al., 2009) , as well as from brain to optic nerve (Shindler et al., 2008 (Shindler et al., , 2011 , has been reported following intracranial inoculation with MHV-A59 or RSA59 and may serve as one mechanism for virus to avoid immune surveillance; however, axonal spread to optic nerve has not been well examined following intranasal inoculation.