The role of mast cells in the restriction of inflammation after brain trauma and spinal cord injury

• Applicant: Professor Dr. Sven Hendrix
• Subject Area: Dermatology
• Term: from 2009 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 124272490

In the last funding period, we demonstrated that mast cells (MC) may exert protective effects in the central nervous system (CNS) after traumatic brain injury (TBI) and spinal cord injury (SCI). We found that MC-deficient mice display increased inflammation, astrogliosis and neurodegeneration after CNS trauma. We provide evidence that mast cell-specific proteases (MCP) degrade inflammatory factors such as MCP-1. In the next funding period, we will investigate 1. which other MCP degrade inflammation-associated factors and 2. whether MCP degrade extracellular matrix (ECM) components which inhibit axonal regeneration. In the planned project, we will investigate the role that MCPs play in controlling of CNS inflammation and ECM degradation in organotypic brain slices in vitro, as well as in models of TBI and SCI in vivo. In these trauma models we will analyze selected MCP-deficient mouse lines and administer recombinant MCPs or MCP inhibitors in wildtype mice. Furthermore, we will search for additional MCP substrates in these mouse lines compared to wildtype mice by using the cytometric bead array and western blotting. Promising candidates will be tested in degradation assays followed by MALDI-TOF analysis. By addressing these questions we wish to further characterize and exploit the therapeutic potential of MCP in CNS trauma.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1394: Mast Cells - Promoters of Health and Modulators of Disease
• International Connection: Belgium