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  • Increased PPAR-δ Signaling Protects the Spinal Cord Microvasculature and Complements the Benefits of Surgical Decompression in Cervical Spondylotic Myelopathy (CSM)

    Final Number:
    363

    Authors:
    Spyridon K Karadimas MD PhD; Michael G. Fehlings MD PhD FRCSC FACS

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2013 Annual Meeting

    Introduction: While successful surgical intervention can arrest the progression of CSM, most patients are left with significant residual neurological impairment. Recent evidence shows that the chronic cervical spinal cord compression disrupts the blood spinal cord barrier (BSCB) and causes endothelial cell loss. PPAR-d is known to preserve endothelial cell and promotes BSCB integrity in ischemia. Here, we hypothesized that increased PPAR-d signaling would protect the spinal cord microvasculature and provide complementary benefits to surgical decompression in a novel CSM mouse model.

    Methods: In this study we exploited a novel mouse CSM model. The experimental groups and plan are depicted in Figure 1. Decompression was achieved by removal of the C6 lamina and the compression formation underneath it. Gait analysis was performed using CatWalk. Immunohistochemistry, western blot and PCR were also performed. To evaluate the BSCB integrity Evans-blue injection was performed. ANOVAs were used for statistical analysis.

    Results: All groups have MRI confirmation of similar degrees of cord compression. At 6 weeks post-decompression D+G group showed significant increased hindlimb and forelimb stride length compared to G, D and C groups (p<0.05 for each comparison). Similarly, the forelimb and hindlimb stance phase duration was significantly decreased in D+G group compared to the G, D and C groups (p<0.05 for each comparison). These results indicate that the combinatorial treatment attenuated forelimbs and hindlimb spasticity compared to decompression alone treatment. Moreover, decreased BSCB disruption and increased number of endothelial cells was found to D+G group compared to the other experimental groups (p<0.05 for each comparison). Finally the administration of PPAR-d agonist decreased the oxidative damage caused by decompression surgery (p<0.05 for D+G vs D).

    Conclusions: These results demonstrate that PPAR-d agonism has microvasculo- and neuro-protective effects and in synergy with the spinal cord decompression leads to better functional outcomes than the decompression alone in CSM.

    Patient Care: The current research suggest for a first time a potential microvasculo- and neuroprotective treatment for CSM. This treatment could complement the benefits of the surgical decompression.

    Learning Objectives: Inform the spine care community that under the chronic compression the cervical spinal cord microvasculature is disrupted. The protection of the former by PPAR-d agonism promotes neuroprotection and neurobehavioural recovery in CSM. Finally, the combination of PPAR-d agonist and surgical decompression results in better functional outcomes compared to decompression alone.

    References:

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