Download Macrophage cytotoxicity post spinal cord injury

Macrophage cytotoxicity post spinal cord injury
Amelioration of Macrophage Cytotoxicity After Spinal Cord Injury: Impact on
Secondary Injury and Axonal Regeneration
Chief Investigator: Associate Professor David Howells
Associate Investigator: Dr Peter Batchelor
Lead Organisation: University of Melbourne
TAC Neurotrauma Funding: $547,052
Project Start Date: 14 May 2007 – 31 October 2010
Background:
In the weeks following trauma to the spinal cord, the size of the injured region
substantially expands as a result of inflammation mediated by cells called
macrophages. These cells are normally involved in digesting and cleaning up debris
after injury and appear to kill neighbouring healthy cells during this process. In
preliminary work, we have established that certain chemicals are able to switch off the
killing activity of macrophages in culture. The aim of this study is to determine if
these same chemicals are able to switch off the killing activity of macrophages in rats
after spinal cord injury.
Macrophages are also involved in the subsequent repair of the wounded spinal cord.
Unfortunately repair results in the production of a dense scar which acts as a barrier to
nerve fibres trying to grow back through the injury site. Because we are altering the
function of macrophages, we wish to determine whether the composition of the scar is
altered and whether some nerve fibres are permitted to grow across the injured region.
Aims:
The aim of this study is to determine if chemicals called interleukins are able to
switch off the killing activity of macrophages in rats after spinal cord injury.
Methods:
Rats received a mild experimental spinal cord injury followed by infusion of the antiinflammatory cytokines interleukin 4 and 10 or both. The influence of these
compounds on inflammatory cell and scar composition as well as on wound size,
nerve cell regeneration and behavioural outcome was then assessed.
Results:
Cytokine treatment resulted in reduced toxicity of infiltrating inflammatory cells.
However, there was no benefit of the infusion of these anti-inflammatory cytokines on
the amount of damage to the spinal cord, nor were behaviour outcomes improved. The
wound scar was not visibly affected; however, regeneration of nerve fibres through
the wound site was improved to some extent.
Conclusions:
The anti-inflammatory cytokines interleukin 4 and 10 do not appear to be immediately
useful in the treatment of spinal cord injury.
Publications:
BATCHELOR PE, TAN S, WILLS T, PORRITT MJ & HOWELLS DW. Comparison of
inflammation in the brain and spinal cord following mechanical injury. J Neurotrauma.
2008;25(10):1217-25.
Presentations:
KERR NF, BATCHELOR PE, HOWELLS DW. The effects of a subcutaneous infusion of interleukin4 and interleukin-10 on inflammatory macrophages after spinal cord contusion injury. IBRO World
Congress of Neuroscience meeting; 2007 July 12-17, Melbourne, Australia.
KERR NF, BATCHELOR PE, HOWELLS DW. A breach in the dura matter affects scar formation and
composition after spinal cord injury. Australian Neuroscience Society Meeting; 2008 January 27-30,
Hobart, Australia.