Microglial TRPV4 deficiency improves recovery after spinal cord injury by preventing excessive microgliosis. (R-12226)

Spinal cord injury (SCI) is a severe life-altering condition resulting in irreversible loss of function. It is associated with severe tissue damage due to inflammation occurring at the injury site. Microglia are important immune cells of the spinal cord and essential early after the injury to clear the area from damaged components. However, they might stimulate excessive inflammation, thereby impairing recovery. Interestingly, the absence of TRPV4 is associated with a decreased number of microglial cells and reduced inflammation at the injury site, improving recovery after SCI. TRPV4 is a membrane channel sensitive to mechanical stimuli and it is implicated in several processes such as cell growth and cellular uptake of compounds from the damaged area. Of note, mechanical stimuli and inflammatory mediators present in the damaged tissue are direct activators of the receptor. Therefore, we hypothesize that recovery after SCI is improved by preventing TRPV4-induced excessive microglial activity. This will be studied in an SCI mouse model with a microglia-specific TRPV4 deficiency. In addition, we will use microglial cells to unravel the role of TRPV4 in microglial activities, including cell growth, the release of inflammation-inducing molecules and uptake of damaged compounds from the injury site. Altogether, we expect to provide a comprehensive view of microglial TRPV4 contribution, underscoring the value of TRPV4 as a therapeutic target for SCI treatment.

Keywords:Neurology

Disciplines:Cell movement, Cell signalling, Cell physiology, Cellular interactions and extracellular matrix