Introduction: Cervical spondylotic myelopathy (CSM), which is caused by progressive compression of the cervical cord due to spondylosis, is the most common cause of spinal cord impairment worldwide. While decompression demonstrates efficacy, the physiological consequences of decompression have yet to be studied. Here, we used a preclinical rat CSM model to characterize the physiological changes in spinal cord after decompression and to examine the synergistic effects of decompression and riluzole.
Methods: Spinal cord blood flow (SCBF) before and after surgical decompression in CSM animals was assessed using FAIR MRI Levels of oxidative damage and the forelimb and forepaw function were evaluated before and after decompression. Then, we developed a novel experimental paradigm to examine the effects of combinatorial strategy consists of decompression and riluzole. Gait analysis was performed weekly using a computerized kinematic assessment (CatWalk). Immunohistochemistry was used for detection of apoptosis, astrogliosis, motoneuronal survival and axonal integrity. Data were analyzed using ANOVA with Bonferonni post-hoc analysis.
Results: We demonstrated increased SCBF, clinical decline and oxidative damage soon after decompression indicating ischemia-reperfusion injury (IRI). In vivo and in vitro studies confirmed that decompression-mediated IRI could be prevented by riluzole administration. Moreover, combinatorial strategy markedly improves hand and gait function and attenuates below-level neuropathic pain compared to decompression alone. Finally, combined strategy reduces axonal damage, cellular apoptosis and motoneuronal injury in the cervical area and suppressing microglial activation in lumbar dorsal horns.
Conclusions: The results of this study are the first to identify the development of a physiological injury in the cervical spinal cord induced by the mainstay of current treatment of CSM. This study paved the way for CSM Protect clinical trial, which examines the synergy of decompression and riluzole in human CSM.
Patient Care: this research informs the clinicians about a biological injury associated with the mainstay of current treatment of CSM. Moreover, it provides scientific evidence proposing a new combinatorial treatment for CSM.
Learning Objectives: development of combinatorial treatment for CSM