Abstract for Sydney Spinal Symposium 2020
*Baxter, C; Gamble, J; Brown, D.A.
*Presenting author
Introduction
Spinal cord injury (SCI) has devastating effects on 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 $2 billion. Despite the heavy burden, there has been little improvement in therapies over the past decade. GDF15, a TGF-β superfamily member, regulates inflammatory responses and is neurotrophic in insult. Recently, we demonstrated that GDF15 enhanced recovery from traumatic spinal cord injury (SCI) by promoting cellular infiltrates at the injury site. We observed an increase in the number of astrocytes around the injury area of the spinal cord tissue 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), and double-blinded locomotion assessment was performed on days 7, 14, 21 and 28 post SCI using the Basso Mouse Scale (BMS). Tissue was harvested at 28 days and stained for GFAP, an astrocyte marker, to investigate cellular changes in the injury area. In separate experiments, primary astrocyte cultures from Tg and WT mice were investigated for changes in astrocyte reactivity in an in vitro model of CNS injury. GDF15 Tg mice had superior locomotor recovery, increase in astrocytes, and reduced secondary tissue loss in the injury area at 28 days compared to their KO and WT counterparts.
Conclusion
Overall, the findings suggest astrocytes as a major CNS cell type involved in the clinical outcome of SCI and are a promising target for novel therapies with GDF15. Further investigation into the role of astrocytes in traumatic SCI is warranted.