Journal
SPINE
Volume 43, Issue 6, Pages E327-E333Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/BRS.0000000000002357
Keywords
apoptosis; autophagy; cell death mechanisms; C-terminal domain of tetanus toxin; spinal cord injury; tetanus toxin
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Funding
- The Turkish Orthopedic Research Council (TORC/TOAK), a branch of the Turkish Society of Orthopedics and Traumatology (TSOT/TOTBID) [07.09.2015-30]
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Study Design. Experimental animal study investigating the efficacy of C-terminal domain of tetanus toxin application as neuroprotective effects on rat brain in a model of spinal cord injury (SCI). Objective. The aim of the present study was to investigate the possible role of C-terminal domain of tetanus toxin (Hc-TeTx) on cell death mechanisms including apoptosis and autophagy following SCI. Summary of Background Data. Traumatic SCI can lead to posttraumatic inflammation, oxidative stress, motor neuron apoptosis, necrosis, and autophagy of tissue. To promote and enhance recovery after SCI, recent development of devices and therapeutic interventions are needed. Methods. Twenty-eight adult rats were divided into four groups (n = 7 each) as follows: sham, trauma (SCI), SCI thorn Hc-TeTx, and SCI thorn methylprednisolone groups. The functional neurological deficits due to the SCI were assessed by behavioral analysis using the Basso, Beattie and Bresnahan (BBB) open-field locomotor test. The alterations in pro-/anti-apoptotic and autophagy related-protein levels were measured by Western blotting technique. Results. In this study, Hc-TeTx promotes locomotor recovery and motor neuron survival of SCI rats. Hc-TeTx also decreased expression of bax, bad, bak, cleaved caspase-3, Ask1, and autophagy-related proteins including Atg5 and LC3II in brain. Our study provides an evidence that cell death mechanisms play critical roles in SCI and that the nontoxic peptides including Hc-TeTx may exert protective effect and decrease cell death following SCI. Conclusion. Our preliminary findings suggest a possible therapeutic agent to improve survival after spinal cord trauma, but further analysis are still needed to evaluate the difference between acute and chronic injuries.
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