Nitric Oxide in TMEV

Oleszak, Emilia L.; Kuzmak, Jacek; Varadhachary, Arun; Katsetos, Christos D.

We and others have previously investigated the role of inducible nitric oxide synthase (iNOS) on early acute and late chronic demyelinating disease induced by Theiler’s Murine Encephalomyelitis Virus (TMEV). Infection of susceptible SJL mice with this virus serves as an excellent model of virus-induced demyelinating disease, such as multiple sclerosis (MS). iNOS transcripts and protein were detected in brains and spinal cords of TMEV-infected SJL mice during early acute disease, which resembles polioencephalomyelitis. Similar level of expression of iNOS has been found in resistant B6 mice, which develop only early acute disease. Weak iNOS staining was detected in reactive astrocytes and in leptomeningeal infiltrates in TMEV-infected SJL mice at 42 days post infection (p.i.), corresponding to early phase of chronic demyelinating disease, but not at 66 and 180 days p.i. corresponding to advanced and terminal stages of the disease, respectively. Results from other laboratories demonstrated that, blocking of NO by treatment of TMEV-infected SJL mice with amino guanidine (AG), a specific inhibitor of NO resulted in delay of late chronic demyelinating disease. However this protective effect of NO inhibitor depended on the temporal phase of the disease, type of cells expressing iNOS and the time of administration of AG. The results from our laboratory suggests that NO expressed during early acute disease is beneficial to the host through induction of apoptosis of infiltrating T cells and resolution of encephalitis, but its role in myelin/oligodendrocytes damage during late chronic demyelinating disease is not clear and it may depend on availability of superoxide and formation of peroxynitrite.