Introduction
Spinal cord injury (SCI) can severely impact upon a patient’s quality of life and imposes a large social and economic burden on society. The total annual cost of spinal cord injury in Australia is estimated to be over $3 billion. Despite this, there has been little improvement in therapies over the past decade. GDF15, a TGF-β superfamily member, regulates inflammatory responses and is neurotrophic. Recently, we demonstrated that GDF15 enhanced recovery from traumatic spinal cord injury (SCI) in a mouse model of spinal cord injury. We observed an increase in the inflammatory cellular infiltrate in Tg mice in addition to increased tissue sparing.
Methods and results
Severe contusive SCI (70 kilo dyne force) was induced in wild type (WT), GDF15 transgenic (Tg), and GDF15 knockout (KO) mice. Double-blinded locomotion assessment was performed on days 7, 14, 21 and 28 post SCI using the Basso Mouse Scale (BMS). Tissue and blood was harvested at 28 days to investigate cellular changes in the injury area. GDF15 Tg mice had superior locomotor recovery, and an increase in inflammatory cellular infiltrate, compared to their KO and WT counterparts. This inflammatory cellular infiltrate included an increased frequency of macrophages and dendritic cells (DCs).
Conclusion
Overall, the findings suggest that the increase in the inflammatory cellular infiltrate following injury may improve the clinical outcome of SCI and macrophages and other innate immune cells are a promising target for novel therapies with GDF15.