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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.

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.

A 62-year-old male presented with a thoracic intradural-extramedullary metastasis from lung cancer. He complained of walking difficulty and bilateral lower leg numbness. He had a past history of lung adenocarcinoma three years prior. Thoracic spine magnetic resonance imaging showed that the tumor occupied the right subarachnoid space and spinal nerve roots had shifted to the left side at Th12. He was diagnosed with cauda equina syndrome by an intradural-extramedullary tumor. Surgery was performed (Th12 laminectomy) and we opened the dura mater and arachnoid membrane. The tumor was in the right side and was removed. After the operation, his neurological condition soon improved and he could walk with a cane. By four moths postoperatively, a metastatic brain tumor occurred and he had to use a wheel chair. He died one year after surgery. Immunohistochemical staining was positive for thyroid transcription factor-1 in both the lung adenocarcinoma and intradural-extramedullary tumor. We diagnosed a metastatic tumor. Including the present case, 102 cases of a metastatic intradural-extramedullary tumor have been reported and, thus, the condition may not be rare. In more than twenty years there have only been two case studies, which recommended both operative and non-operative methods. We reviewed the validity of an operation base on the prognosis and surgical results of previous reports. The average life expectancy was 8.6 months. The functional improvement rate was 78%. We recommend an operation for an intradural-extramedullary metastatic tumor because it improves the quality of a patients’ short life.

While 22 articles have reported on sacral stress fractures, it is a rare injury and its etiology is not well known. We present the case of a 16-year-old male who presented with low back pain in 2015. He was a high school soccer player with a previous history of a bilateral L5 lumbar spondylolysis in 2014. The patient refrained from soccer and wore a brace for six months. Two months after restarting soccer, he again complained of low back pain. After 1 year, a lumbar spine computed tomography revealed the bone union of the spondylolysis. At his first visit to our hospital, his general and neurological conditions were normal and laboratory data were within the normal range. Sacral coronal magnetic resonance imaging (MRI) of the left sacral ala revealed an oblique lineal signal void surrounding bone marrow edema. Based on his symptoms, sports history, and MRI, he was diagnosed with a sacral stress fracture. He again refrained from soccer; his low back pain soon improved, and, after 1 year, the abnormal signal change had disappeared on sacral MRI. Recurrent low back pain case caused by a sacral stress fracture occurring after the bone union of lumbar spondylolysis is uncommon.