• BMB Reports
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• 제55권1호
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• pp.20-29
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• 2022

Stem cell-based therapy is a promising approach for treating a variety of disorders, including acute brain insults and neurodegenerative diseases. Stem cells such as mesenchymal stem cells (MSCs) secrete extracellular vesicles (EVs), circular membrane fragments (30 nm-1 ㎛) that are shed from the cell surface, carrying several therapeutic molecules such as proteins and microRNAs. Because EV-based therapy is superior to cell therapy in terms of scalable production, biodistribution, and safety profiles, it can be used to treat brain diseases as an alternative to stem cell therapy. This review presents evidences evaluating the role of stem cell-derived EVs in stroke, traumatic brain injury, and degenerative brain diseases, such as Alzheimer's disease and Parkinson' disease. In addition, stem cell-derived EVs have better profiles in biocompatibility, immunogenicity, and safety than those of small chemical and macromolecules. The advantages and disadvantages of EVs compared with other strategies are discussed. Even though EVs obtained from native stem cells have potential in the treatment of brain diseases, the successful clinical application is limited by the short half-life, limited targeting, rapid clearance after application, and insufficient payload. We discuss the strategies to enhance the efficacy of EV therapeutics. Finally, EV therapies have yet to be approved by the regulatory authorities. Major issues are discussed together with relevant advances in the clinical application of EV therapeutics.

• Journal of Korean Neurosurgical Society
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• 제44권5호
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• pp.295-302
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• 2008

Objective: Premorbid demographic backgrounds of injured individuals are likely to reflect more accurately the status of patients with traumatic brian injury (TBI) than clinical factors. However, the concrete study about the relationship between the demographic factors and neurocognitive function in TBI patients has not been reported. The object of this study was to evaluate the effect of premorbid demographic factors on the recovery of neurocognitive function following TBI. Methods: From July 1998 to February 2007, 293 patients (male: 228, female: 65) with a history of head injury, who had recovered from the acute phase, were selected from our hospital to include in this study. We analyzed the effect of premorbid demographic factors including age, sex, educational level and occupation on the recovery of neurocognitive function in each TBI subgroup as defined by Glasgow Coma Scale (GCS) score. Intelligence and memory are components of neurocognitive function, and the Korean Wechsler Intelligence Scale (K-WAIS) and the Korean memory assessment scale (K-MAS) were used in this study. The results were considered significant at p<0.05. Results: The higher level of education was a good prognostic factor for intelligence regardless of GCS score and younger age group showed a better result for memory with an exception of severe TBI group. In the severe TBI group, the meaningful effect of demographic factors was not noted by the cause of influence of severe brain injury. Conclusion: The demographic factors used in this study may be helpful for predicting the precise prognosis and developing an appropriate rehabilitation program for TBI patients.

• Journal of Medicine and Life Science
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• 제17권1호
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• pp.7-15
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• 2020

The field triage guidelines have been widely implemented in the Korean trauma system. This study aimed to evaluate and validate whether it is reliable to use the field triage guidelines for predicting severe traumatic brain injury (TBI) and traumatic spinal injury (TSI) patients. This study retrospectively analyzed in-hospital cohort registries of all TBI and TSI patients, who visited the emergency department (ED) of the Jeju National University Hospital from 1 January 2013 to 31 December 2015. The primary outcome was defined as TBI and TSI patients with an injury severity score (ISS)>15. Secondary outcomes were defined as cases in which one or more of the following conditions: in-hospital death, ISS>15, admission to the intensive care unit, emergency surgery. We enrolled 14,889 TBI and TSI patients who visited ED, of which 7,966 (53.5%) were triage positive. The overall sensitivity, specificity and area under the curve (AUC) of the full cumulative field triage guidelines step's model (Step 1+3+4 criteria) for primary outcome were 82.8%, 47.0%, and 0.646, respectively. In the results for secondary outcomes, the specificity did not show a significant difference, but the sensitivity decreased to 66.5% and AUC to 0.568. The results of this study suggest that further optimization of the field triage guidelines is needed to identify high-risk TBI and TSI patients.

• The Korean Journal of Physiology and Pharmacology
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• 제19권6호
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• pp.491-497
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• 2015

Traumatic brain injury (TBI) is a major cause of mortality and long-term disability, which can decrease quality of life. In spite of numerous studies suggesting that Epigallocatechin-3- gallate (EGCG) has been used as a therapeutic agent for a broad range of disorders, the effect of EGCG on TBI remains unknown. In this study, a weight drop model was established to evaluate the therapeutic potential of EGCG on TBI. Rats were administered with 100 mg/kg EGCG or PBS intraperitoneally. At different times following trauma, rats were sacrificed for analysis. It was found that EGCG (100 mg/kg, i.p.) treatment significantly reduced brain water content and vascular permeability at 12, 24, 48, 72 hour after TBI. Real-time PCR results revealed that EGCG inhibited TBI-induced IL-$1{\beta}$ and TNF-${\alpha}$ mRNA expression. Importantly, CD68 mRNA expression decreasing in the brain suggested that EGCG inhibited microglia activation. Western blotting and immunohistochemistry results showed that administering of EGCG significantly inhibited the levels of aquaporin-4 (AQP4) and glial fibrillary acidic protein (GFAP) expression. TBI-induced oxidative stress was remarkably impaired by EGCG treatment, which elevated the activities of SOD and GSH-PX. Conversely, EGCG significantly reduced the contents of MDA after TBI. In addition, EGCG decreased TBI-induced NADPH oxidase activation through inhibition of $p47^{phox}$ translocation from cytoplasm to plasma membrane. These data demonstrate that EGCG treatment may be an effective therapeutic strategy for TBI and the underlying mechanism involves inhibition of oxidative stress.

• Journal of Trauma and Injury
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• 제31권2호
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• pp.51-57
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• 2018

Purpose: Patients with diffuse axonal injury experience various disabilities and have a high cost of treatment. Recent researches have revealed the underlying mechanism and pathogenesis of diffuse axonal injury. This study aimed to investigate the correlation between the radiological grading of diffuse axonal injury and the clinical outcomes of patients. Methods: From January 2011 to December 2016, among 294 patients with traumatic brain injury, 44 patients underwent magnetic resonance imaging (MRI). A total of 18 patients were enrolled in this study except for other cerebral injuries, such as cerebral hemorrhage or hypoxic brain damage. Demographic data, clinical data, and radiological findings were retrospectively reviewed. The grading of diffuse axonal injury was analyzed based on patient's MRI findings. Results: For the most severe diffuse axonal injury patients, prolonged intensive care unit (ICU) stay (p=0.035), hospital stay (p=0.012), and prolonged mechanical ventilation (p=0.030) were observed. However, there was no significant difference in healthcare-associated infection rates between MRI grading (p=0.123). Massive transfusion, initial hemoglobin and lactate levels, and MRI gradings were found to be highly significant in predicting the duration of unconsciousness. Conclusions: This study showed that patients with high grade diffuse axonal injury have prolonged ICU stays and significantly longer hospital stays. Deteriorated mental patients with high energy injuries should be evaluated to identify diffuse axonal injuries by using an appropriate imaging tool, such as MRI. It will be important to predict the duration of consciousness recovery using MRI scans.

• The Korean Journal of Pain
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• 제33권1호
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• pp.1-2
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• 2020

• Journal of Trauma and Injury
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• 제36권1호
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• pp.49-52
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• 2023

Blunt carotid artery injury can lead to impaired brain perfusion due to ischemic stroke and thromboembolic events. To reduce the risk of potential neurological complications, it is critical to determine the diagnosis and management protocol as quickly as possible after a detailed clinical examination. This report presents successful surgical treatment of a young male patient who developed a traumatic left common carotid artery thrombosis after a motor vehicle accident.

• Journal of Korean Neurosurgical Society
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• 제45권3호
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• pp.176-178
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• 2009

Traumatic brainstem hemorrhage after blunt head injury is an uncommon event. The most frequent site of hemorrhage is the midline rostral brainstem. The prognosis of these patients is poor because of its critical location. We experienced a case of traumatic brainstem hemorrhage. A 41-year-old male was presented with drowsy mentality and right hemiparesis after blunt head injury. Plain skull radiographs and brain computerized tomography scans revealed a depressed skull fracture, epidural hematoma, and hemorrhagic contusion in the right parieto-occipital region. But, these findings did not explain the right hemiparesis. T2-weighted magnetic resonance (MR) image of the cervical spine demonstrated a focal hyperintense lesion in the left pontomedullary junction. Brain diffusion-weighted and FLAIR MR images showed a focal hyperintensity in the ventral pontomedullary lesion and it was more prominent in the left side. His mentality and weakness were progressively improved with conservative treatment. We should keep in mind the possibility of brainstem hemorrhage if supratentorial lesions or spinal cord lesions that caused neurological deficits in the head injured patients are unexplainable.

• Journal of Korean Neurosurgical Society
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• 제29권4호
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• pp.461-470
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• 2000

Objective : Many investigators have demonstrated the protective effects of hypothermia following traumatic brain injury(TBI) in both animals and humans. It has long been recognized that mild to moderate hypothermia improves neurologic outcomes as well as reduces histologic and biochemical sequelae after TBI. In this study, two immunohistochemical staining using terminal deoxynucleotidyl-transferase-mediated biotin dUTP nick end labeling(TUNEL), staining of apoptosis, and ${\beta}$-amyloid precursor protein(${\beta}$-APP), a marker of axonal injury, were done and the authors evaluated the protective effects of hypothermia on axonal and neuronal injury after TBI in rats. Material and Method : The animals were prepared for the delivery of impact-acceleration brain injury as described by Marmarou and colleagues. TBI is achieved by allowing of a weight drop of 450gm, 1 m height to fall onto a metallic disc fixed on the intact skull of the rats. Fourty Sprague-Dawley rats weighing 400 to 450g were subjected to experimental TBI induced by an impact-acceleration device. Twenty rats were subjected to hypothermia after injury, with their rectal temperatures maintained at $32^{\circ}C$ for 1 hour. After this 1-hour period of hypothermia, rewarming to normothermic levels was accomplished over 30-minute period. Following 12 hours, 24 hours, 1 week and 2 weeks later the animals were killed and semiserial sagittal sections of the brain were reacted for visualization of the apoptosis and ${\beta}$-APP. Results : The density of ${\beta}$-APP marked damaged axons within the corticospinal tract at the pontomedullary junction and apoptotic cells at the contused cerebral cortex were calculated for each animal. In comparison with the untreated controls, a significant reduction in ${\beta}$-APP marked damaged axonal density and apoptotic cells were found in all hypothermic animals(p<0.05). Conclusion : This study shows that the posttraumatic hypothermia result in substantial protection in TBI, at least in terms of the injured axons and neurons.

• Journal of Trauma and Injury
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• 제32권4호
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• pp.195-201
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• 2019

Purpose: This study was conducted to investigate the usefulness of a polyester urethane dural substitute (Neuro-Patch^®, B. Braun, Boulogne, France) as an anti-adhesion agent in subsequent cranioplasty by analyzing the use of Neuro-Patch^® during decompressive craniectomy in traumatic brain injury patients. Methods: We retrospectively analyzed patients with traumatic brain injury who underwent decompressive craniectomy followed by cranioplasty from January 2015 to December 2018. Patients were analyzed according to whether they received treatment with Neuro-Patch^® or not (Neuro-Patch^® group, n=71; control group, n=55). Patients' baseline characteristics were analyzed to identify factors that could affect cranioplasty results, including age, sex, hypertension, diabetes mellitus, use of antiplatelet agents or anticoagulant medication, the interval between craniectomy and cranioplasty, and the type of bone used in cranioplasty. The cranioplasty results were analyzed according to the following factors: operation time, blood loss, postoperative hospitalization period, surgical site infection, and revision surgery due to extra-axial hematoma. Results: No significant difference was found between the two groups regarding patients' baseline characteristics. For the cranioplasty procedures, the operation time (155 vs. 190 minutes, p=0.003), intraoperative blood loss (350 vs. 450 mL, p=0.012), and number of surgical site infections (4 vs. 11 cases, p=0.024) were significantly lower in the Neuro-Patch^® group than in the control group. Conclusions: The use of Neuro-Patch^® was associated with a shorter operation time, less blood loss, and a lower number of surgical site infections in subsequent cranioplasties. These results may provide a rationale for prospective studies investigating the efficacy of Neuro-Patch^®.