Administration of the GLP-1 receptor agonist exenatide in rats improves functional recovery after spinal cord injury by reducing endoplasmic reticulum stress.

After spinal cord injury (SCI), endoplasmic reticulum (ER) stress has been reported to be an integral part of the secondary injury process that causes apoptosis of glial cells, leading to remyelination failure. This report focuses on exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist widely used to treat diabetes, as a potential agent to improve functional outcome after SCI by improving the ER stress response. Exenatide administered subcutaneously immediately after injury and 7 days later in a rat model of moderate contusive SCI revealed significant improvement in hindlimb function without any hypoglycemia. Changes in the expression of glucose regulatory protein 78 (GRP78), an endoplasmic reticulum chaperone that protects against ER stress, and C/EBP homologous transcription factor protein (CHOP), a pro-apoptotic transcription factor in the apoptosis pathway were examined as indices of ER stress. We found that administration of exenatide after SCI suppressed CHOP while increasing GRP78 in the injured spinal cord, leading to a significant decrease in tissue damage and a significant increase in oligodendrocyte progenitor cell survival. This study suggests that administration of exenatide after SCI decreases ER stress and improves functional recovery without any apparent side-effects.

Comparison of the clinical outcomes of intramedullary nailing between impending and completed pathological fractures caused by metastatic femoral tumors from solid cancers.

BACKGROUND: We examined the treatment outcomes following intramedullary nailing in patients with metastatic femoral tumors, excluding those from hematological malignancies. METHODS: We retrospectively evaluated treatment outcomes following intramedullary nailing between patients who underwent preventative surgery compared with those who had surgery following pathological fracture. Patients who underwent preventative surgery (Mirels' score ≥8) were allocated to the impending fracture group (n = 11) and those who underwent surgery after pathological fracture were allocated to the completed fracture group (n = 20). RESULTS: Duration of surgery was significantly shorter in the impending fracture group than in the completed fracture group. Median blood loss was significantly less, and the median duration of hospital stay was significantly shorter in the impending fracture group than in the completed fracture group. Among patients who died following surgery, the median postoperative survival duration was significantly longer in the impending fracture group than in the completed fracture group. Significantly more patients regained walking function in the impending fracture group than in the completed fracture group. Regarding complications, infection occurred in one patient in the completed fracture group. No implant damage was observed in either group. CONCLUSIONS: Patients with metastatic femoral tumors who underwent intramedullary nailing in the impending fracture group had better postoperative survival and gait function, less blood loss, and shorter durations of surgery and hospital stay than those in the completed fracture group. These findings indicate the importance of early diagnosis and treatment and value of treatment prior to fracture occurrence.

Compression of the Median Nerve and Ulnar Nerve's Deep Palmar Branch by a Ganglion Cyst in the Carpal Tunnel: A Case Report.

CASE: A 39-year-old woman presented with a ganglion cyst in the carpal tunnel simultaneously compressing the right median nerve and the deep palmar branch of the ulnar nerve. During surgery, the soft tissue was exposed under the median nerve and on the deep palmar branch of the ulnar nerve running transversely in the deep area of the carpal tunnel. CONCLUSION: Simultaneous compression of the median nerve and deep palmar branch of the ulnar nerve is extremely rare; however, such a pathoanatomical relationship must be considered while examining a patient because these nerves are located close to each other.

The relationship between inflammasomes and the endoplasmic reticulum stress response in the injured spinal cord.

STUDY DESIGN: Animal study. OBJECTIVES: The aim of this study is to investigate the influence of inflammasomes in the injured spinal cord of a rat spinal cord injury model. SETTING: University laboratory in Kanagawa, Japan. METHODS: A thoracic contusion spinal cord injury (SCI) was induced in female Sprague Dawley rats using an IH-impactor to create a moderate injury group (LI) and a severe injury group (HI). Using a sham group as a control, the injured spinal cords were removed at several time points after injury to evaluate the levels of inflammasome component proteins in the injured spinal cord by immunohistochemistry and Western Blot. RESULTS: Western blot analyses revealed that the expression of inflammasome component proteins leucine-rich repeat protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-2 significantly increased in the SCI animals compared to the sham animals. Thioredoxin interacting protein (TXNIP), which is a protein induced by ER stress that activates the NLRP3 inflammasome, was also significantly higher in the SCI animals. Immunohistochemistry revealed significantly higher expression of NLRP3, ASC, and Caspase-2 in oligodendrocyte progenitor cells (OPCs) of the SCI groups compared to astrocytes of the SCI groups and OPCs of the sham group. CONCLUSIONS: Inflammasome component protein expression increases after SCI in association with increased ER stress. OPCs had significantly higher levels of inflammasome proteins compared to astrocytes, which may be associated with the high rates of OPC cell death after SCI.

Amiloride Promotes Oligodendrocyte Survival and Remyelination after Spinal Cord Injury in Rats.

After spinal cord injury (SCI), secondary injury results in an expanding area of glial cell apoptosis. Oligodendrocyte precursor cells (OPCs) actively proliferate after SCI, but many of these cells undergo apoptosis. One of the factors that exacerbates secondary injury is endoplasmic reticulum (ER) stress. In this study, we tested the effects of amiloride treatment on the fate of OPCs during secondary injury in rats. Amiloride is an FDA-approved diuretic for treating hypertension, which in rats enhances ER stress response and suppresses the apoptosis of glial cells after SCI. A severe contusive SCI was induced in Sprague-Dawley rats using an infinite horizon (IH)-impactor (200 kdyne). Beginning 24 h after SCI, 10 mg/kg of amiloride or phosphate buffered saline (PBS) was intraperitoneally administered daily for a period of 14 days. At 7, 14, 28, and 56 days after SCI, animals were subsequently euthanized in order to analyze the injured spinal cord. We labeled proliferating OPCs and demonstrated that amiloride treatment led to greater numbers of OPCs and oligodendrocytes in the injured spinal cord. Increased myelin basic protein (MBP) expression levels were observed, suggesting that increased numbers of mature oligodendrocytes led to improved remyelination, significantly improving motor function recovery.

Open Wedge Osteotomy with Ulnar Shortening for Madelung Deformity Using a Computer-Generated Template.

A variety of osteotomies have been reported to correct Madelung deformity using plain radiographs. However, evaluation of the deformity using 2-dimensional plain radiography is difficult because of its complex 3-dimensional nature. Therefore, we performed corrective osteotomy using recently developed 3D simulation technology on an adult woman with Madelung deformity, and achieved an excellent outcome. In this study, we calculated the amount of parallel displacement as well as the rotational angle for more precise correction, and performed open wedge osteotomy. Furthermore, we performed concurrent ulnar shortening. An exaggerated radial inclination was observed in the posteroanterior radiograph. A palmar shift of the carpus and dorsal dislocation of the ulnar head were observed in the lateral radiograph. In the preoperative findings, radial inclination (RI), volar tilt (VT), and ulnar variance (UV) were 35°, 40°, and 12 mm, respectively. The wrist showed improvement, with an RI of 25°, VT of 14°, and UV of 0 mm. At present, 14 months after surgery, there has been no loss of correction, instability of the ulnar head, or pain on the ulnar side. The procedure resulted in improvements in the protrusion and pain in the ulnar portion of the patient's wrist. Based on this result, we believe that accurate corrective osteotomy with ulnar shortening should be performed for Madelung deformity.