Minocycline is neuroprotective in many experimental models of
neurodegenerative diseases and central nervous system (CNS) injury but has not previously been tested in a model of
viral encephalitis. Experimental
infection of neonatal mice with neurotropic reoviruses is a classic model for studying the pathogenesis of
viral encephalitis. Intracerebral inoculation of serotype 3 reovirus strain Dearing (T3D) in neonatal mice results in lethal
encephalitis caused by neuronal apoptosis throughout the CNS.
Minocycline significantly delayed death in mice to 11.6 +/- 0.9 days post-
infection vs. 8.6 +/- 0.7 days post-
infection in controls (P < 0.01). Virus-induced CNS injury, apoptosis, viral titer and
antigen expression were significantly decreased in the brains of
minocycline-treated mice on 6 and 8 days post-
infection compared to controls. Virus-induced injury and viral titer in
minocycline-treated infected mice at 11 days post-
infection were similar to those seen in untreated T3D-infected mice at 8 days post-
infection. Little microglial or astrocytic invasion of brain regions with viral injury was found at any time-point in untreated or
minocycline-treated mice, suggesting that in this model system the
neuroprotective effect exerted by
minocycline is more likely due to its anti-apoptotic properties rather than its capacity to inhibit microglial activation and limit
gliosis. These findings, similar to those reported for
neurodegenerative diseases, indicate that
minocycline does not prevent development of fatal reovirus
encephalitis but delays disease onset and progression, suggesting that
minocycline treatment may provide a useful adjunctive
therapy in
viral CNS infections.