Impacts of external rotators and the ischiofemoral ligament on preventing excessive internal hip rotation: a cadaveric study.

BACKGROUND: This study examined the biomechanics of preventing excessive internal hip joint rotation related to the hip flexion angle. METHOD: An intramedullary nail with a circular plate equipped with a protractor was installed in the femur of nine normal hips. The circular plate was pulled by 3.15 Nm of force in the internal rotation direction. The external rotators were individually resected, finally cutting the ischiofemoral ligament. The cutting order of the external rotators differed on each side to individually determine the internal rotation resistance. The external rotators were resected from the piriformis to the obturator externus in the right hips and the reverse order in the left hips. Traction was performed after excising each muscle and ischiofemoral ligament. Measurements were taken at 0°, 30°, and 60° of hip flexion, and the differences from baseline were calculated. RESULTS: For the right hip measurements, the piriformis and ischiofemoral ligament resection significantly differed at 0° of flexion (p = 0.02), each external rotator and the ischiofemoral ligament resections significantly differed at 30° of flexion (p < 0.01), and the ischiofemoral ligament and piriformis and inferior gemellus resections significantly differed at 60° of flexion (p = 0.04 and p = 0.02, respectively). In the left hips, the ischiofemoral ligament and obturator externus, inferior gemellus, and obturator internus resections significantly differed at 0° of flexion (p < 0.01, p < 0.01, and p = 0.01, respectively), as did each external rotator and the ischiofemoral ligament resections at 30° of flexion (p < 0.01). CONCLUSION: The ischiofemoral ligament primarily restricted the internal rotation of the hip joint. The piriformis and obturator internus may restrict internal rotation at 0° and 60° of flexion.

Chaperone-Mediated Autophagy after Spinal Cord Injury.

Autophagy is the degradation process of dysfunctional intracellular components and has a crucial function in various human diseases. There are three different types of autophagy: macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA). CMA is a major route for the elimination of cellular aberrant proteins and can provide a cytoprotective effect. The present study investigated the expression of lysosome-associated membrane protein type 2A (LAMP2A), which is the hallmark of CMA activity, in damaged neural tissue after spinal cord injury (SCI) in mice. The number of LAMP2A-expressing cells was significantly increased at the lesion following SCI. The increased number of LAMP2A-positive cells was observed from 24 h and peaked at 3 days after injury. A western blot analysis confirmed that the level of LAMP2A protein was significantly increased in the injured spinal cord compared with the uninjured cord. On double staining for LAMP2A and different neural cell type markers, the increased expression of LAMP2A was observed in neurons, astrocytes, oligodendrocytes, and microglia/macrophages following injury. An electron microscopic analysis showed that secondary lysosomes were increased in damaged neurons at the lesion site. Immunoelectron microscopy revealed that the gold particles with anti-LAMP2A antibody were frequently localized at the secondary lysosomes in the injured site. These findings indicated that CMA was clearly activated in damaged neural tissue after SCI. The activation of CMA may contribute to the elimination of intracellular aberrant proteins and exert a neuroprotective effect following SCI.

Low-energy extracorporeal shock wave therapy promotes BDNF expression and improves functional recovery after spinal cord injury in rats.

Low-energy extracorporeal shock wave therapy (ESWT) has been used to treat various human diseases. Previous studies have shown that low-energy ESWT promotes the release of various cell growth factors and trophic factors from the cells surrounding the target lesion. The aim of the current study was to determine whether the application of low-energy ESWT upregulates the expression of brain-derived neurotrophic factor (BDNF) and reduces neural tissue damage and functional impairment using a rat model of thoracic spinal cord contusion injury. We found that low-energy ESWT promoted BDNF expression in the damaged neural tissue. The expression of BDNF was increased in various neural cells at the lesion. Additionally, low-energy ESWT increased the area of spared white matter and the number of oligodendrocytes in the injured spinal cord compared with untreated control animals. There were more axonal fibers around the injured site after the application of low-energy ESWT than control. Importantly, low-energy ESWT improved the locomotor functions evaluated by both the BBB scale and ladder rung walking test in addition to the sensory function measured using a von Frey test. Moreover, the electrophysiological assessment confirmed that the conductivity of the central motor pathway in the injured spinal cord was restored by low-energy ESWT. These findings indicate that low-energy ESWT promotes BDNF expression at the lesion site and reduces the neural tissue damage and functional impairment following spinal cord injury. Our results support the potential application of low-energy ESWT as a novel therapeutic strategy for treating spinal cord injury.

B-RAFV600E Inhibitor Dabrafenib Attenuates RIPK3-Mediated Necroptosis and Promotes Functional Recovery after Spinal Cord Injury.

The receptor-interacting protein kinase 3 (RIPK3) is a key regulator of necroptosis and is involved in various pathologies of human diseases. We previously reported that RIPK3 expression is upregulated in various neural cells at the lesions and necroptosis contributed to secondary neural tissue damage after spinal cord injury (SCI). Interestingly, recent studies have shown that the B-RAFV600E inhibitor dabrafenib has a function to selectively inhibit RIPK3 and prevents necroptosis in various disease models. In the present study, using a mouse model of thoracic spinal cord contusion injury, we demonstrate that dabrafenib administration in the acute phase significantly inhibites RIPK3-mediated necroptosis in the injured spinal cord. The administration of dabrafenib attenuated secondary neural tissue damage, such as demyelination, neuronal loss, and axonal damage, following SCI. Importantly, the neuroprotective effect of dabrafenib dramatically improved the recovery of locomotor and sensory functions after SCI. Furthermore, the electrophysiological assessment of the injured spinal cord objectively confirmed that the functional recovery was enhanced by dabrafenib. These findings suggest that the B-RAFV600E inhibitor dabrafenib attenuates RIPK3-mediated necroptosis to provide a neuroprotective effect and promotes functional recovery after SCI. The administration of dabrafenib may be a novel therapeutic strategy for treating patients with SCI in the future.