Phase-Dependent Expression Of Matrix-Metalloproteinases And Their Inhibitors In Demyelinating Canine Distemper Encephalitis

Matrix-metalloproteinases (MMPs) are zinc- and calcium-dependent enzymes, that cleave molecules of the extracellular matrix and thus are able to open the blood-brain-barrier and affect myelin. Their inhibitors (TIMPs) are important candidates for the therapy of demyelinating diseases. To establish an immunohistochemical profile of MMP and TIMP expressions in plaque variants in dogs with spontaneous demyelinating distemper encephalitis, paraffin-embedded cerebella were detected employing the ABC method with a panel of 9 polyclonal (anti-MMP-1, -3, -7, -9, -12, -13, -14, -TIMP-1, and -2) and 2 monoclonal antibodies (anti-latent MMP-2, and MMP-11). MMPs and TIMPs especially MMP-9, -11, -12, -13, -14, and TIMP-1, and -2 were most prominently up-regulated in acute and subacute non-inflammatory lesions, and double-labelling techniques stressed, that they were mainly expressed by astrocytes and brain macrophages/microglia. In subacute inflammatory and chronic plaques, a moderate to strong decrease of MMP and TIMP expressions compared to acute lesions was observed and, additionally, invading perivascular mononuclear cells were MMP-, and TIMP-positive. Prominent MMPs and TIMPs in these phases were MMP-11, -12, -13, and -14, and, confined to chronic lesions, TIMP-2. Summarized, there was a phase-dependent expression of MMPs and TIMPs in demyelinating canine distemper encephalitis, and MMP-12 seemed to play a central role in the demyelination process.