Minocycline delays disease onset and mortality in reovirus encephalitis.
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.
Richardson-Burns
Sarah M
SM
Neuroscience Program, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
Tyler
Kenneth L
KL
D017668:Age of Onset; D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D018792:Encephalitis, Viral / Q000188:drug therapy / Q000401:mortality*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D012089:Mammalian orthoreovirus 3 / Q000502:physiology; D051379:Mice; D008911:Minocycline / Q000627:therapeutic use*; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology / Q000821:virology; D011897:Random Allocation; D012088:Reoviridae Infections / Q000188:drug therapy / Q000401:mortality*; D013997:Time Factors; D019562:Viral Load / Q000379:methods
D000900:Anti-Bacterial Agents; D005904:Glial Fibrillary Acidic Protein; D008911:Minocycline