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  • Intrathecal Infusion of Decorin to Sub-acute Contusion Spinal Cord Injury Promotes Robust Functional Recovery

    Final Number:
    196

    Authors:
    Kenneth Minor; Kyle Jasper; Jeannette E. Davies PhD; Stephen Davies PhD

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2012 Annual Meeting

    Introduction: Decorin is a small leucine-rich repeat protein found in many tissues throughout the body that has been shown to have anti-inflammatory and anti-fibrotic properties. Direct infusion of decorin into rodent cerebral cortex or spinal cord injuries can suppress fibrotic scarring and the expression of multiple axons growth inhibitory chondroitin sulphate proteoglycans (CSPGs) and semaphorin 3A(1-3). In addition, decorin has also been shown to “desensitize” neurons to the inhibitory effects of both CSPGs and myelin associated molecules4 in vitro. To further explore the therapeutic potential of decorin in treating CNS injuries, we tested the ability of decorin to promote recovery in a clinically relevant sub-acute (12 days post injury) rodent cervical spinal cord contusion injury model.

    Methods: Unilateral contusion injuries were carried out on adult Sprague-Dawley rats at the C4/C5 spinal level. At 12 days after injury, animals were split into three groups. The decorin treatment group received an intrathecal infusion of human recombinant decorin core protein in saline over a period of 7 days. The remaining control spinal cord injured rats received either intrathecal infusion of saline vehicle or a catheter and no treatment. Functional recovery was assessed at time points ranging from 1 to 7 weeks post treatment with horizontal ladder and CatWalk gait analyses.

    Results: Robust functional recovery was observed in decorin treated rats in both tests compared to control spinal cord injured rats that failed to show significant improvements. Histological analysis of decorin treated cords revealed robust increases in corticospinal tract collaterals and synaptic plasticity within spinal gray matter below sites of injury compared to controls.

    Conclusions: Our results demonstrate that intrathecal infusion of decorin at a clinically relevant time point of twelve days post injury can promote functional recovery and provide further support for the development of decorin as a therapy for the injured human spinal cord.

    Patient Care: This research will lead to the development of new therapies to repair the traumatically injured or diseased adult central nervous system.

    Learning Objectives: 1. The participants will be able to name different axon growth inhibitory elements of CNS scar tissue 2. The participants will be able to name pro-inflammatory cytokines that promote CNS scar formation 3. The participants will be able to discuss regulation of scar formation and plasticity of neural circuits by Decorin.

    References: 1. Logan, A., Baird, A., and Berry, M. (1999) Decorin attenuates gliotic scar formation in the rat cerebral hemisphere. Exp. Neurol. 159(2):504-10. 2. Davies, JE., Tang, X., Denning, JW., Archibald, SJ., Davies, SJA. (2004) Decorin suppresses neurocan, brevican, phosphacan and NG2 expression and promotes axon growth across adult rat spinal cord injuries. Eur J Neurosci. 19(5):1226-42. 3. Minor, KH., Bournat, JC., Toscano, N., Giger, RJ., Davies, SJA. (2010 Epub) Decorin, erythroblastic leukaemia viral oncogene homologue B4 and signal transducer and activator of transcription 3 regulation of semaphorin 3A in central nervous system scar tissue. Brain 134(Pt4):1140-55.

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