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In a previous study, we utilized a proteomic approach and found a significant reduction in phosphatidylethanolamine-binding protein 1 (PEBP1) protein level in the spinal cord at 3 h after ischemia. In the present study, we investigated the role of PEBP1 against oxidative stress in NSC34 cells in vitro, and ischemic damage in the rabbit spinal cord in vivo. We generated a PEP-1-PEBP1 fusion protein to facilitate the penetration of blood-brain barrier and intracellular delivery of PEBP1 protein. Treatment with PEP-1-PEBP1 significantly decreased cell death and the induction of oxidative stress in NSC34 cells. Furthermore, administering PEP-1-PEBP1 did not show any significant side effects immediately before and after ischemia/reperfusion. Administration of PEP-PEBP1 improved the Tarlov's neurological score at 24 and 72 h after ischemia, and significantly improved neuronal survival at 72 h after ischemia based on neuronal nuclei (NeuN) immunohistochemistry, Flouro-Jade B staining, and western blot study for cleaved caspase 3. PEP-1-PEBP1 administration decreased oxidative stress based on malondialdehyde level, advanced oxidation protein products, and 8-iso-prostaglandin F2α in the spinal cord. In addition, inflammation based on myeloperoxidase level, tumor necrosis factor-α level, and high mobility group box 1 level was decreased by PEP-1-PEBP1 treatment at 72 h after ischemia. Thus, PEP-1-PEBP1 treatment, which decreases oxidative stress, inflammatory cytokines, and neuronal death, may be an effective therapeutic strategy for spinal cord ischemia. [ABSTRACT FROM AUTHOR]

Objective: Although adult spinal deformity (ASD) surgery aims to restore and maintain alignment, proximal junctional kyphosis (PJK) may occur. While existing scoring systems predict PJK, they predominantly offer a generalized 3-tier risk classification, limiting their utility for nuanced treatment decisions. This study seeks to establish a personalized risk calculator for PJK, aiming to enhance treatment planning precision., Methods: Patient data for ASD were sourced from the Korean spinal deformity database. PJK was defined a proximal junctional angle (PJA) of ≥ 20° at the final follow-up, or an increase in PJA of ≥ 10° compared to the preoperative values. Multivariable analysis was performed to identify independent variables. Subsequently, 5 machine learning models were created to predict individualized PJK risk post-ASD surgery. The most efficacious model was deployed as an online and interactive calculator., Results: From a pool of 201 patients, 49 (24.4%) exhibited PJK during the follow-up period. Through multivariable analysis, postoperative PJA, body mass index, and deformity type emerged as independent predictors for PJK. When testing machine learning models using study results and previously reported variables as hyperparameters, the random forest model exhibited the highest accuracy, reaching 83%, with an area under the receiver operating characteristics curve of 0.76. This model has been launched as a freely accessible tool at: (https://snuspine.shinyapps.io/PJKafterASD/)., Conclusion: An online calculator, founded on the random forest model, has been developed to gauge the risk of PJK following ASD surgery. This may be a useful clinical tool for surgeons, allowing them to better predict PJK probabilities and refine subsequent therapeutic strategies.

Objective: Notch receptors are heterodimeric transmembrane proteins that regulate cell fate, such as differentiation, proliferation, and apoptosis. Dysregulated Notch pathway signaling has been observed in glioblastomas, as well as in other human malignancies. Nerve growth factor (NGF) is essential for cell growth and differentiation in the nervous system. Recent reports suggest that NGF stimulates glioblastoma proliferation. However, the relationship between NGF and Notch1 in glioblastomas remains unknown. Therefore, we investigated expression of Notch1 in a glioblastoma cell line (U87-MG), and examined the relationship between NGF and Notch1 signaling., Methods: We evaluated expression of Notch1 in human glioblastomas and normal brain tissues by immunohistochemical staining. The effect of NGF on glioblastoma cell line (U87-MG) was evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. To evaluate the relationship between NGF and Notch1 signaling, Notch1 and Hes1 expression were evaluated by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. To confirm the effects of NGF on Notch1 signaling, Notch1 and Hes1 small interfering RNAs (siRNAs) were used., Results: In immunohistochemistry, Notch1 expression was higher in glioblastoma than in normal brain tissue. MTT assay showed that NGF stimulates U87-MG cells in a dose-dependent manner. RT-PCR and Western blot analysis demonstrated that Notch1 and Hes1 expression were increased by NGF in a dose-dependent manner. After transfection with Notch1 and Hes1 siRNAs, there was no significant difference between controls and 100 nM NGF-β, which means that U87-MG cell proliferation was suppressed by Notch1 and Hes1 siRNAs., Conclusion: These results indicate that NGF stimulates glioblastoma cell proliferation via Notch1 signaling through Hes 1.

In the present study, we used immunohistochemistry and western blot analysis to examine changes in the levels and cellular localization of iron, heavy chain ferritin (ferritin-H), and transferrin in the gerbil hippocampal CA1 region from 30 minutes to 7 days following transient forebrain ischemia. Relative to sham controls, iron reactivity increased significantly in the stratum pyramidale and stratum oriens at 12 hours following ischemic insult, transiently decreased at 1-2 days and then increased once again within the CA1 region at 4-7 days after ischemia. One day after ischemia, ferritin-H immunoreactivity increased significantly in the stratum pyramidale and decreased at 2 days. At 4-7 days after ischemia, ferritin-H immunoreactivity in the glial components in the CA1 region was significantly increased. Transferrin immunoreactivity was increased significantly in the stratum pyramidale at 12 hours, peaked at 1 day, and then decreased significantly at 2 days after ischemia. Seven days after ischemia, Transferrin immunoreactivity in the glial cells of the stratum oriens and radiatum was significantly increased. Western blot analyses supported these results, demonstrating that compared to sham controls, ferritin H and transferrin protein levels in hippocampal homogenates significantly increased at 1 day after ischemia, peaked at 4 days and then decreased. These results suggest that iron overload-induced oxidative stress is most prominent at 12 hours after ischemia in the stratum pyramidale, suggesting that this time window may be the optimal period for therapeutic intervention to protect neurons from ischemia-induced death.

In this study, we investigated the effects of streptozotocin-induced type 1 diabetes on antioxidant-like protein-1 immunoreactivity, protein carbonyl levels, and malondialdehyde formation, a marker for lipid peroxidation, in the hippocampus. For this study, streptozotocin (75 mg/kg) was intraperitoneally injected into adult rats to induce type 1 diabetes. The three experimental parameters were determined at 2, 3, 4 weeks after streptozotocin treatment. Fasting blood glucose levels significantly increased by 20.7-21.9 mM after streptozotocin treatment. The number of antioxidant-like protein-1 immunoreactive neurons significantly decreased in the hippocampal CA1 region, but not the dentate gyrus, 3 weeks after streptozotocin treatment compared to the control group. Malondialdehyde and protein carbonyl levels, which are modified by oxidative stress, significantly increased with a peak at 3 weeks after malondialdehyde treatment, and then decreased 4 weeks after malondialdehyde treatment. These results suggest that neurons in the hippocampal CA1 region, but not the dentate gyrus, are susceptible to oxidative stress 3 weeks after malondialdehyde treatment.

Objective: Subdural hygroma (SDG) is a complication occurring after head trauma that may occur secondary to decompressive craniectomy (DC). However, the mechanism underlying SDG formation is not fully understood. Also, the relationship between the operative technique of DC or the decompressive effect and the occurrence and pathophysiology of SDG has not been clarified. Purpose of this study was to investigate the risk factors of SDG after DC in our series., Methods: From January 2004 to December 2008, DC was performed in 85 patients who suffered from traumatic brain injury. We retrospectively reviewed the clinical and radiological features. For comparative analysis, we divided the patients into 2 groups : one group with SDG after craniectomy (19 patients; 28.4% of the total sample), the other group without SDG (48 patients; 71.6%). The risk factors for developing SDG were then analyzed., Results: The mean Glasgow Outcome Scale (GOS) scores at discharge of the groups with and without SDG were 2.8 and 3.1, respectively (p<0.0001). Analysis of radiological factors showed that a midline shift in excess of 5 mm on CT scans was present in 19 patients (100%) in the group with SDG and in 32 patients (66.7%) in the group without SDG (p<0.05). An accompanying subarachnoid hemorrhage (SAH) was seen in 17 patients (89.5%) in the group with SDG and in 29 patients (60.4%) in the group without SDG (p<0.05). Delayed hydrocephalus accompanied these findings in 10 patients (52.6%) in the group with SDG, versus 5 patients (10.4%) in the group without SDG (p<0.05). On CT, compression of basal cisterns was observed in 14 members (73.7%) in the group with SDG and in 18 members of the group without SDG (37.5%) (p<0.007). Furthermore, tearing of the arachnoid membrane, as observed on CT, was more common in all patients in the group with SDG (100%) than in the group without SDG (31 patients; 64.6%) (p<0.05)., Conclusion: GOS showed statistically significant difference in the clinical risk factors for SDG between the group with SDG and the group without SDG. Analysis of radiological factors indicated that a midline shifting exceeding 5 mm, SAH, delayed hydrocephalus, compression of basal cisterns, and tearing of the arachnoid membrane were significantly more common in patients with SDG.

Objective: Allelic losses or loss of heterozygosity (LOH) at many chromosomal loci have been found in the cells of meningiomas. The objective of this study was to evaluate LOH at several loci of different chromosomes (1p32, 17p13, 7q21, 7q31, and 22q13) in different grades of meningiomas., Methods: Forty surgical specimens were obtained and classified as benign, atypical, and anaplastic meningiomas. After DNA extraction, ten polymorphic microsatellite markers were used to detect LOH. Medical and surgical records, as well as pathologic findings, were reviewed retrospectively., Results: LOH at 1p32 was detected in 24%, 60%, and 60% in benign, atypical, and anaplastic meningiomas, respectively. Whereas LOH at 7q21 was found in only one atypical meningioma. LOH at 7q31 was found in one benign meningioma and one atypical meningioma. LOH at 17p13 was detected in 4%, 40%, and 80% in benign, atypical, and anaplastic meningiomas, respectively. LOH at 22q13 was seen in 48%, 60%, and 60% in benign, atypical, and anaplastic meningiomas, respectively. LOH results at 1p32 and 17p13 showed statistically significant differences between benign and non-benign meningiomas., Conclusion: LOH at 1p32 and 17p13 showed a strong correlation with tumor progression. On the other hand, LOH at 7q21 and 7q31 may not contribute to the development of the meningiomas.

Objective: To characterize perioperative biomechanical changes after thoracic spine surgery., Methods: Fifty-eight patients underwent spinal instrumented fusions and simple laminectomies on the thoracolumbar spine from April 2003 to October 2008. Patients were allocated to three groups; namely, the laminectomy without fusion group (group I, n = 17), the thoracolumbar fusion group (group II, n = 27), and the thoracic spine fusion group (group III, n = 14). Sagittal (ADS) and coronal (ADC) angles for adjacent segments were measured from two disc spaces above lesions at the upper margins, to two disc spaces below lesions at the lower margins. Sagittal (TLS) and coronal (TLC) angles of the thoracolumbar junction were measured from the lower margin of the 11th thoracic vertebra body to the upper margin of the 2nd lumbar vertebra body on plane radiographs. Adjacent segment disc heights and disc signal changes were determined using simple spinal examinations and by magnetic resonance imaging. Clinical outcome indices were determined using a visual analog scale., Results: The three groups demonstrated statistically significant differences in terms of angle changes by ANOVA (p < 0.05). All angles in group I showed significantly smaller angles changes than in groups II and III by Turkey's multiple comparison analysis. Coronal Cobb's angles of the thoracolumbar spine (TLC) were not significantly different in the three groups., Conclusion: Postoperative sagittal balance is expected to change in the adjacent and thoracolumbar areas after thoracic spine fusion. However, its prevalence seems to be higher when the thoracolumbar spine is included in instrumented fusion.