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.

Intranasal as well as intracranial inoculation of JHM has been shown to induce similar symptoms in BALB/C mice (Robbins et al., 1991) . Similarly, intracranial inoculation has been well used as a method for MHV-A59 to cause the biphasic disease (Das Sarma et al., 2000 , 2002 , while a higher dose of MHV-A59 is required to reach the same level of inflammation in CEACAM-/-mice when inoculated through the nasal route (Blau et al., 2001; Hemmila et al., 2004) . With intracranial inoculation, the inflammation is not limited to brain and spinal cord. MHV-A59 and recombinant strain RSA59 cause inflammation in optic nerve with subsequent demyelination of optic nerve and RGC loss (Shindler et al., 2008 (Shindler et al., , 2011 . Studies of isogenic recombinant strains RSA59 and RSMHV2 of demyelinating strain (MHV-A59) and non-demyelinating strain (MHV2), respectively, containing enhanced green fluorescent protein (EGFP) have elaborated the mechanisms of demyelination and axonal loss and have helped in tracking and tracing of virus in vitro as well as in vivo (Das Sarma et al., 2009) . RSA59 can cause demyelination, but RSMHV2 cannot, which makes it a suitable control to determine the cellular and molecular basis of demyelination in mice.