Doxycycline treatment decreases morbidity and mortality of murine neurocysticercosis: evidence for reduction of apoptosis and matrix metalloproteinase activity.
Murine neurocysticercosis is a parasitic infection transmitted through the direct ingestion of Taenia solium eggs, which differentially disrupts the barriers that protect the microenvironment of the central nervous system. Among the host factors that are involved in this response, matrix metalloproteinases (MMPs) have been recently described as important players. Doxycycline is a commonly prescribed antimicrobial drug that acts as an anti-inflammatory agent with broad inhibitory properties against MMPs. In this study, we examined the effects of doxycycline treatment in a murine model of neurocysticercosis. Animals treated with doxycycline exhibited reduced morbidity and mortality throughout the course of infection. Although similar levels of leukocyte infiltration were observed with both treatment regimens, doxycycline appeared to provide improved conditions for host survival, as reduced levels of apoptosis were detected among infiltrates as well as in neurons. As an established MMP blocker, doxycycline reduced the degradation of junctional complex proteins in parenchymal vessels. In addition, doxycycline treatment was associated with an overall reduction in the expression and activity of MMPs, particularly in areas of leukocyte infiltration. These results indicate that a broad-range inhibitor of MMPs promotes host survival and suggest the potential of doxycycline as a therapeutic agent for the control of inflammatory responses associated with neurocysticercosis.
Alvarez
Jorge I
JI
One UTSA Circle, San Antonio, TX 78249, USA.
Krishnamurthy
Janani
J
Teale
Judy M
JM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D004318:Doxycycline / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008807:Mice, Inbred BALB C; D020019:Neurocysticercosis / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D041201:Taenia solium / Q000187:drug effects*
D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D004318:Doxycycline