Oral Presentation Sydney Spinal Symposium 2019

MIC-1/GDF15 overexpression is associated with increased functional recovery in traumatic spinal cord injury.    (#14)

Jo Gamble 1 , Masoud G Hassanpour 1 , David A Brown 1
  1. Centre for Immunology and Allergy Research, Neuroinflammation Research Group , Westmead Institute for Medical Research , Sydney, NSW, Australia

Spinal cord injury has devastating effects and imposes a large amount of social and economic burden on society. The total cost of spinal cord injury in Australia is estimated to be $2 billion annually. Despite this, there has been little improvement in treatments over the past decade. GDF15, a TGFb superfamily member, regulates inflammatory responses and is neurotrophic. Recently, we demonstrated that GDF15 enhanced recovery from traumatic spinal cord injury (SCI). In addition to its anti-inflammatory properties, GDF15 is directly neurotrophic to spinal motor neurons and prevents their apoptosis.  

Severe contusive SCI (70 kilo dyne) was induced in wild type (WT), MIC-1/GDF15 transgenic (Tg), and MIC-1/GDF15 knockout (KO), and locomotion was assessed on days 7,14,21, and 28 post SCI using the Basso Mouse Scale (BMS). MIC-1/GDF15 Tg mice had superior locomotor recovery and reduced secondary tissue loss at 28 days compared to their KO and WT counterparts. Overexpression of MIC-1/GDF15 coincided with increased expression of MCP-1/CCL2 at the lesion site (28 days post SCI) and enhanced recruitment of inflammatory cells to the injured spinal cord. This inflammatory cellular infiltrate included an increased frequency of macrophages, mDCs, pDCs, and CD8α+ DCs that mostly preceded recruitment of CD4+ and CD8+ T cells.

Overall, these findings suggest MIC-1/GDF15 is associated with beneficial changes in the clinical course of SCI that are characterised by altered post-injury inflammation and improved functional outcome. Further investigation of MIC-1/GDF15 as a novel therapeutic target for traumatic SCI is warranted.