Epidermal growth factor regulates apoptosis and oxidative stress in a rat model of spinal cord injury.

Spinal cord injury (SCI) leads to vascular damage and disruption of blood-spinal cord barrier which participates in secondary nerve injury. Epidermal growth factor (EGF) is an endogenous protein which regulates cell proliferation, growth and differention. Previous studies reported that EGF exerts neuroprotective effect in spinal cord after SCI. However, the molecular mechanisms underlying EGF-mediated protection in different regions of nervous system have not shown yet. In this study, we aimed to examine possible anti-apoptotic and protective roles of EGF not only in spinal cord but also in brain following SCI. Twenty-eight adult rats were divided into four groups of seven animals each as follows: sham, trauma (SCI), SCI + EGF and SCI + methylprednisolone (MP) 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 protein levels and antioxidant enzyme activities were measured in spinal cord and frontal cortex. In our study, EGF promoted locomotor recovery and motor neuron survival of SCI rats. EGF treatment significantly decreased Bax and increased Bcl-2 protein expressions both in spinal cord and brain when compared to SCI group. Moreover, antioxidant enzyme activities including catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx) were increased following EGF treatment similar to MP treatment. Our experiment also suggests that alteration of the ratio of Bcl-2 to Bax may result from decreased apoptosis following EGF treatment. As a conclusion, these results show, for the first time, that administration of EGF exerts its protection via regulating apoptotic and oxidative pathways in response to spinal cord injury in different regions of central nervous system.

Neuroprotective Effects of C-terminal Domain of Tetanus Toxin on Rat Brain Against Motorneuron Damages After Experimental Spinal Cord Injury.

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 + Hc-TeTx, and SCI + 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. LEVEL OF EVIDENCE: N/A.