101 The Sodium Channel/Gluatamate Blocker Riluzole is Complementary to Decompression in a Preclinical Experimental Model of Cervical Spondylotic Myelopathy (CSM): Implications for Translational Clinical Application


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Abstract

INTRODUCTION:While successful surgical intervention can arrest the progression of CSM, most patients are left with significant residual neurological impairment. Based on promising results in our laboratory implicating excitotoxic secondary injury in the pathobiology of CSM, we hypothesized that the sodium-glutamate blocker riluzole would provide complementary benefits to surgical decompression in an animal model of CSM.METHODS:The spinal cords of Sprague-Dawley rats were slowly and progressively compressed over a 12 week period by introducing an aromatic polyether strip under the C6 lamina. Rats were randomly and blindly allocated to the following experimental groups (Fig. 1): control; riluzole alone; decompression alone and riluzole with decompression. Decompression was achieved at 6 weeks post-implantation by C6 laminectomy and resection of the extradural pathology. Data were analyzed using ANOVA with Bonferonni post-hoc analysis. Quantitative MRI, kinematic gait analysis, lesion morphometry and immunohistochemistry were undertaken.RESULTS:All groups had MRI confirmation of similar degrees of cord compression. Successful decompression was demonstrated on MRI at 10 weeks post-initial surgery (Fig. 2A). At 12 weeks post-surgery the forelimb stride length and forelimb dexterity were significantly increased in the decompression-riluzole group compared to the decompression only group (P = 0.002). Moreover, riluzole alone improved gait parameters compared to the control group (P = 0.048) (Fig. 2B,C). Confocal immunohistochemistry showed that riluzole combined with decompression leads to increased preservation of the corticospinal tract, decreased astrogliosis and reduced apoptosis of motoneurons when compared with decompression alone.CONCLUSION:These results demonstrate for the first time that riluzole acts synergistically with decompression to enhance functional and neuroanatomical outcomes in a preclinical model of CSM. These promising results have paved the way for a randomized controlled trial to evaluate the combined effects of decompression and riluzole in patients with CSM.

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