Spinal Cord Recovery in the Opossum

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					Spinal Cord Recovery in the Opossum
Mechanisms of Recovery Following Spinal Cord Injury in Neonatal
Mondodelphis Domestica (South American Opossum)

Chief Investigator: Professor Norman Saunders
Associate Investigators: Associate Professor Kate Dziegielewska, Dr Samantha
Richardson, Professor Dalton Dietrich, Dr Helen Stolp, Dr Jessie Truettner, Dr Paul
Samollow
Lead Organisation: University of Melbourne
TAC Neurotrauma Funding: $1,095,114
Project Dates: 1 February 2007 - 30 June 2010

Aims:
This project was based on our previous findings published in international journals,
that when the spinal cord of neonatal South American opossums is injured by
complete transection, the animals show a remarkable degree of recovery and normal
development, but not when they are injured at an older age. The aim of this project
was to identify differences in gene activity and levels of the proteins they make in
response to injury to the spinal cord at different ages. Understanding the nature of the
genetic control of the response to injury in neonatal animals, may make it possible to
identify mechanisms that can be modified in older animals (and eventually patients) to
revert the nervous system back to a state when repair is possible.

Methods:
We have used a combination of proteomics, RNA-sequencing and PCR together with
behavioural and morphological studies.

Results:
We have completed a major study of gene and protein expression in one week old
(when the regenerative recovery from spinal injury occurs) and 4 week animals (when
regenerative recovery does not occur) The results show that there are indeed
differential changes in gene activity and protein levels at different postnatal ages
following spinal cord injury; these include genes/proteins that are involved in the
innate and acquired inflammatory responses, as well as those involved in cell death,
growth of nerve fibres and metabolic adaptations to injury.

Conclusions:
The response to spinal injury is a multifaceted biological problem. This project aimed
at identifying factors that are upstream of regulatory genes and proteins involved in
major metabolic pathways that are involved in control of the response of the central
nervous system to injury. We have established and characterised at the molecular,
cellular, morphological and behavioural level an animal model of the response of the
developing spinal cord to injury in which in vivo manipulation of identified targets
should be possible.
Publications:

None

Presentations:

WILLS TE, KERR NF, KATZ M, HOWELLS DW. AND BATCHELOR PE. Corticospinal tract
sprouting in the injured adult spinal cord following cellular implantation in the motor cortex. 7th
International Brain Research Organization World Congress; 2007 July 12-16, Melbourne, Australia.

WONG CHY, HERTZOG PJ, HICKEY M, CRACK PJ. Glutathione peroxidase and neural injury.
Australian Vascular Biology Society 15th Annual Scientific Meeting; 2007 September 6-9, Hepburn
Springs, Australia.

SEIFMAN MA, ADAMIDES AA, NGUYEN PN, COOPER DJ, KOSSMANN T, ROSENFELD JV,
MORGANTI-KOSSMANN MC. Temporal profiles of melatonin following severe traumatic brain
injury. 7th International Brain Research Organization World Congress; 2007 July 12-16, Melbourne,
Australia.

SATGUNASEELAN L, NGUYEN P, AGYAPOMAA D, KOSSMANN T, MORGANTI-
KOSSMANN MC. The effect of post-traumatic hypoxia (PTH) on neuroinflammation, protein marker
release and brain metabolism after traumatic brain injury (TBI). 7th International Brain Research
Organization World Congress; 2007 July 12-16, Melbourne, Australia.

SATGUNASEELAN L, NGUYENP, BYE N, AGYAPOMAA D, KOSSMANN T, MORGANTI-
KOSSMANN MC. The diagnostic role of protein markers and cytokines in focal and diffuse traumatic
brain injury (TBI). 7th International Brain Research Organization World Congress; 2007 July 12-16,
Melbourne, Australia.

SAUNDERS N. Mechanisms of recovery following complete spinal transection in postnatal opossums
(Monodelphis domestica) International Brain Research Organisation International Congress on
Neuroscience; 2007 July 12-17, Melbourne, Australia.

HABGOOD M, JOHANSSON PA, CALLAWAY JK, DZIEGIELEWSKA KM, SAUNDERS N.
Improved animal model for studies of spinal cord injury. Australian and New Zealand Spinal Cord
Society Annual Meeting, 2008 November 26-28, Christchurch, New Zealand.

TRUETTNER JS, EK CJ, DZIEGIELEWSKA KM, WAKEFIELD M, O’DONOVAN L, WHEATON
B, DIETRICH WD AND SAUNDERS NR. Age-dependent changes in gene expression and recovery
following complete spinal cord transection in neonatal opossums (Monodelphis domestica). Society for
Neuroscience 38th Annual Meeting; 2008 November 15-19, Washington DC, USA.

JOAKIM EK, TRUETTNER J, DZIEGIELEWSKA KM, O’DONOVAN L, DIETRICH D,
SAUNDERS NR. A novel approach to spinal cord injury: age–dependent changes in gene expression
in neonatal opossums (Monodelphis domestica). Australian & New Zealand Spinal Cord Society; 2008
November 26-28, Christchurch, New Zealand.

NOOR NM, STEER DL, EK CJ, RICHARDSON SJ, SAUNDERS NR. Proteomic analysis of spinal
cord response to injury in the immature Monodelphis domestica. Trauma Melbourne Conference; 2009
November 20-21, Melbourne, Victoria.

TAN F, ZHANG M, O’DONNOVAN L, DOWNES CE, CALLAWAY J, CRACK PJ. The
involvement of sigma receptor agonists in neuroprotection. Australian Neuroscience Society 28th
Annual Scientific Meeting; 2008 January 27-30, Hobart, Australia.
O’DONOVAN L, EK J, TRUETTNER J, DZIEGIELEWSKA K, DIETRICH D, SAUNDERS NR.
(2008). Age–dependent changes in gene expression in neonatal opossums (Monodelphis domestica)
following spinal cord transection. Trauma Melbourne 2008; 2008 November 20-21, Melbourne,
Australia.

WHEATON B, SMITH I, STEER D, EK J, DZIEGIELEWSKA K, NOOR N, TRUETTNER J,
DIETRICH D, SAUNDERS N. Age-dependent changes in protein expression in neonatal opossums
(Monodelphis domestica) following spinal cord transection. Trauma Melbourne 2008; 2008 November
20-21, Melbourne, Australia.

SAUNDERS NR. Translational research in spinal cord injury. Society for Neuroscience; 2009 October
17, Chicago, USA.

CALLAWAY J, HABGOOD M, EK J, JOHANSSON P, DZIEGIELEWSKA K, SAUNDERS N.
Behavioural and histological assessment of residual function and morphology after spinal cord
contusion injury in rats. Joint National/International Neurotrauma Conference; 2009 September 7-11,
Santa Barbara, USA.

WHEATON BJ, CALLAWAY J, EK CJ, TRUETTNER J, DZIEGIELEWSKA KM, DIETRICH WD,
SAUNDERS NR. Recovery from spinal cord transection in neonatal opossums (Monodelphis
domestica). Neurotrauma 2009: 2nd Joint Symposium of the National and International Neurotrauma
Societies; 2009 September 7-11, Santa Barbara, USA.

TRUETTNER JS, EK CJ, DZIEGIELEWSKA KM, WHEATON B, DIETRICH WD, SAUNDERS
NR. Age-dependent changes in gene expression following complete spinal cord transection in neonatal
opossums (Monodelphis domestica) National and International Neurotrauma Societies; 2009
September 7-11, Santa Barbara, USA.

TRUETTNER JS, EK CJ, DZIEGIELEWSKA KM, WHEATON BJ, DIETRICH WD, SAUNDERS
NR. Changes in gene expression following transection of spinal cord in immature Monodelphis
domestica are age-dependent. Society for Neuroscience; 2009 October 17-21, Chicago, USA.

SAUNDERS NR, WAKEFIELD M, EK CJ, LIDDELOW S, TRUETTNER J, WHEATON B,
DIETRICH WD. RNA-seq analysis of gene expression following transection in immature spinal cord
of Monodelphis domestica. Society for Neuroscience; 2009 October 17-21, Chicago, USA.

WHEATON B, CALLAWAY JK, EK CJ, DIETRICH WD, DZIEGIELEWSKA KM, SAUNDERS
NR. Age-related changes in the ability to recover after complete spinal transection in the developing
opossum (Monodelphis domestica). Society for Neuroscience; 2009 October 17-21, Chicago, USA.

DIETRICH WD, TRUETTNER JS, CALLAWAY J, DZIEGIELEWSKA KM, EK CJ, WAKEFIELD
M, WHEATON BJ, SAUNDERS NR. Recovery from complete spinal cord transection in neonatal
opossums (Monodelphis domestica): gene expression, morphology and behavior. Howard H. Steel
Conference; 2009 December 3-5, Orlando, USA.

SAUNDERS N. New treatments for brain and spinal cord injuries. Trauma Melbourne; 2009
November 20-21, Melbourne, Australia.

SAUNDERS NR, TRUETTNER JS, EK CJ, DZIEGIELEWSK KM, WHEATON B, DIETRICH WD.
Age-dependent changes in gene expression following complete spinal cord transection in neonatal
opossums (Monodelphis domestica). National and International Neurotrauma Societies; 2009
September 7-11, Santa Barbara, USA.

WAKEFIELD M, DIETRICH WD, EK CJ, LIDDELOW S, TRUETTNER J, WHEATON B,
SAUNDERS NR. RNA-seq analysis of gene expression following transection in immature spinal cord
of Monodelphis domestica. Society for Neuroscience; 2009 October 17-21, Chicago, USA.
NOOR NM, STEER DI, EK CJ, RICHARDSON SJ, DZIEGIELEWSKA KM, SAUNDERS NR.
Proteomic analysis of spinal cord response to injury at different developmental stages in Monodelphis
domestica. Australian Neuroscience Annual Meeting; 2010 January 31-February 2, Sydney, Australia.

WHEATON BJ, CALLAWAY J, EK J, DZIEGIELEWSKA KM, SAUNDERS NR. On the importance
of supraspinal control in locomotion following spinal cord injury. Society for Neuroscience; 2010
November 13-17, San Diego, USA.

STEER DL, NOOR NM, EK CJ, RICHARDSON SJ, DZIEGIELEWSKA KM, SAUNDERS NR,
SMITH AL. Proteomic analysis of spinal cord injury in early development of Monodelphis domestica.
Human Proteome Organisation Congress; 2010 September 19-23, Sydney, Australia.

WHEATON BJ, CALLAWAY J, EK J, GOODWIN M, DZIEGIELEWSKA KM, SAUNDERS NR.
Functional recovery and morphological repair following spinal cord injury in the developing opossum
(Monodelphis domestica). Australian Neuroscience Annual Meetin; 2010 January 31-February 2,
Sydney, Australia.

				
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