abortus organisms that have access to the CNS can cause inflammation, and that this inflammatory response may lead to tissue damage through, at least, MMP release. To corroborate our hypothesis and give clinical relevance to our findings we investigated whether patients who developed neurobrucellosis exhibit MMP 9 activity in their selleck catalog CSF. MMP 9 activity, Inhibitors,Modulators,Libraries as assayed by zymography, was absent in CSF samples from non infected controls. In contrast, MMP 9 activity was detected in the three CSF samples from neurobrucellosis patients. These patients had a focalized active infec tion process since Brucella organisms were recovered from their CSF samples, which also exhibited high titers of antibodies against B. abortus LPS and Brucella cytoplasmic proteins.

Interestingly, no MMP 9 activity was detected in the CSF sample from a patient suffering brucellosis Inhibitors,Modulators,Libraries without neurological in volvement, in which neither anti Brucella antibodies nor the bacterium were detected. This suggests that, during human brucellosis infection, MMP 9 is released to the CSF only when Brucella invades the CNS. Also, CSF samples from patients who had meningitis caused by infectious agents other than Brucella spp, exhibited MMP 9 activity. These results indicate that astrocyte secreted MMP 9 induced by B. abortus or its lipoproteins could be involved in the pathological manifestations of neurobrucellosis. Discussion We have submitted that in neurobrucellosis, inflammation plays a key role in the mechanism of disease. The importance of the inflammatory response elicited in the CNS by Brucella is that it can lead to irreversible CNS damage of the type that may be attributed to neuronal loss.

Inflammation in the CNS is thought to play a primary role in the pathogenesis of neurodegenerative diseases. Given the likely contribution of inflammation to the pathogenesis of neurobrucellosis, Inhibitors,Modulators,Libraries we hypothesized that, as with some neurodegenerative diseases, these Inhibitors,Modulators,Libraries inflammatory responses may lead to CNS tissue destruction, and eventually loss of glial and neuronal cells. Besides inflammatory cytokines, MMP play an import ant role in the inflammatory damage of CNS, since they can damage the brain parenchyma, the blood brain barrier and even kill neurons. We have already demon strated the central role of the astrocyte in the production of pro inflammatory cytokines that cause cell death upon infection with B.

abortus. Yet, astrocytes as a source of MMP have not been investigated in neurobrucellosis. In this study, we Inhibitors,Modulators,Libraries present evidence indicating that upon infection with B. abortus, as well as other Brucella spe cies, astrocytes secrete MMP 9 to culture Nutlin-3a supernatants. MMP 9 activity was evidenced by zymography and ELISA. MMP activity is counterbalanced by the action of tissue inhibitors including TIMP.