Cisplatin induces changes in the matrix metalloproteinases and their inhibitors in the developing rat cerebellum

The role of matrix metalloproteinases (MMP-3 and MMP-9), tissue inhibitor of MMP (TIMP-2), and GAP-43 (growth-associated-protein) in neocerebellar vermis lobules during postnatal histogenesis was studied after challenge with cisplatin (cisPt). CisPt is one of the most effective and widely used cytotoxic agents in the treatment of a variety of malignancies, in both children and adult patients. A single injection of cisPt to 10-day-old rats altered the spatiotemporal MMP/TIMP expression balance and provoked a decrease in GAP43 immunoreactivity. The imbalance appeared one day (PD11) after cisPt injection, producing disorder of cerebellum histogenesis processes in which MMPs might be involved, i.e. genesis of granule cells, Purkinje cell differentiation and synaptogenesis. Following the early injury, a simultaneous increase in MMP and TIMP expression in the ML was noticed at PD17, likely initiating recovery of Purkinje cell dendrite growth and remodelling processes. However, disturbances at the beginning of recovery phase had emerged, probably due to the down-regulation of GAP-43 after cisPt treatment. The data provide further support for the usefulness of cisPt as a tool for the study of morphological and functional changes in the CNS during postnatal development.

► Cisplatin may induce cytotoxic effects on CNS.
► The cerebellum vulnerability was studied after a single injection of cisplatin.
► Cisplatin altered the spatiotemporal pattern of MMP and TIMP expression.
► Late recovery occurred after treatment during CNS development.