ABSTRACT
This study investigated the mechanism of neurotrophin-3 (NT-3) in promoting spinal cord injury repair through the transforming growth factor-beta (TGF-ß) signaling pathway. A mouse model of spinal cord injury was established. Forty C57BL/6J mice were randomized into model, NT-3, NT-3 + TGF-ß1 and NT-3 + LY364947 groups. The Basso-Beattie-Bresnahan (BBB) scores of the NT-3 and NT-3 + LY364947 groups were significantly higher than the model group. The BBB score of the NT-3 + TGF-ß1 group was significantly lower than NT-3 group. Hematoxylin-eosin staining and transmission electron microscopy showed reduction in myelin sheath injury, more myelinated nerve fibers in the middle section of the catheter, and relatively higher density and more neatly arranged regenerated axons in the NT-3 and NT-3 + LY364947 groups compared with the model and NT-3 + TGF-ß1 groups. Immunofluorescence, TUNEL and Western blot analysis showed that compared with model group, the NEUN expression increased, and the apoptosis and Col IV, LN, CSPG, tenascin-C, Sema 3 A, EphB2 and Smad2/3 protein expression decreased significantly in the NT-3 and NT-3 + LY364947 groups; the condition was reversed in the NT-3 + TGF-ß1 group compared with the NT-3 group. NT-3 combined with TGF-ß signaling pathway promotes astrocyte differentiation, reduces axon regeneration inhibitory molecules, apoptosis and glial scar formation, promotes axon regeneration, and improves spinal cord injury.
ABSTRACT
BACKGROUND: Operative level is a potential biomechanical risk factor for construct failure during anterior fixation for distractive flexion injury. No biomechanical study of this concept has been reported, although it is important in clinical management. METHODS: To explore the mechanism of this concept, a previously validated three-dimensional C2-T1 finite element model was modified to simulate surgical procedure via the anterior approach for treating single-level distractive flexion injury, from C2-C3 to C7-T1. Four loading conditions were used including no-compression, follower load, axial load, and combined load. Construct stability at the operative level was assessed. FINDINGS: Under these loading conditions with the head's weight simulated, segmental stability decreases when the operative level shifts cephalocaudally, especially at C6-C7 and C7-T1, the stress of screw-bone interface increases cephalocaudally, and in the same operative level, the caudal screws always carries more load than the cephalad ones. All these predicted results are consistent with failure patterns observed in clinical reports. In the contrast, under other loading conditions without the weight of head, no obvious segmental divergence was predicted. INTERPRETATION: This study supports that the biomechanical mechanism of this phenomenon includes eccentric load from head weight during sagittal movements and difference of moment arms. Our study suggests that anterior fixation is not recommended for treating distractive flexion injury at the caudal segments of the subaxial cervical spine, especially at C6-C7 and C7-T1, because of the intrinsic instability in these segments. Combined posterior rigid fixation with anterior fixation should be considered for these segments.