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1.
Experimental Neurobiology ; : 120-143, 2021.
Article in English | WPRIM | ID: wpr-898352

ABSTRACT

Central neurocytoma (CN) has been known as a benign neuronal tumor. In rare cases, CN undergoes malignant transformation to glioblastomas (GBM). Here we examined its cellular origin by characterizing differentiation potential and gene expression of CN-spheroids. First, we demonstrate that both CN tissue and cultured primary cells recapitulate the hierarchal cellular composition of subventricular zone (SVZ), which is comprised of neural stem cells (NSCs), transit amplifying progenitors (TAPs), and neuroblasts. We then derived spheroids from CN which displayed EGFR+/ MASH+ TAP and BLBP+ radial glial cell (RGC) characteristic, and mitotic neurogenesis and gliogenesis by single spheroids were observed with cycling multipotential cells. CN-spheroids expressed increased levels of pluripotency and tumor stem cell genes such as KLF4 and TPD5L1, when compared to their differentiated cells and human NSCs. Importantly, Gene Set Enrichment Analysis showed that gene sets of GBM-Spheroids, EGFR Signaling, and Packaging of Telomere Ends are enriched in CN-spheroids in comparison with their differentiated cells. We speculate that CN tumor stem cells have TAP and RGC characteristics, and upregulation of EGFR signaling as well as downregulation of eph-ephrin signaling have critical roles in tumorigenesis of CN. And their ephemeral nature of TAPs destined to neuroblasts, might reflect benign nature of CN.

2.
Article in English | WPRIM | ID: wpr-892147

ABSTRACT

Background@#Although long-term dopamine agonist (DA) therapy is recommended as a first-line treatment for prolactinoma, some patients may prefer surgical treatment because of the potential adverse effects of long-term medication, or the desire to become pregnant. This study aimed to determine whether surgical treatment of prolactinomas could be an alternative to DA therapy. @*Methods@#In this retrospective study, 96 consecutive patients (74 female, 22 male) underwent primary pituitary surgery without long-term DA treatment for prolactinomas at a single institution from 1990 to 2010. All patients underwent primary surgical treatment in the microscopic transsphenoidal approach (TSA). @*Results@#The median age and median follow-up period were 31 (16–73) years and 139.1 (12.2–319.6) months, respectively. An initial overall remission was accomplished in 47.9% (46 of 96 patients, 33 macroadenomas, and 13 microadenomas) of patients. DA dose reduction was achieved in all patients after TSA. A better remission rate was independently predicted by lower diagnostic prolactin levels and by a greater extent of surgical resection. Overall remission at the last follow-up was 33.3%, and the overall recurrence rate was 30.4%. The permanent complication rate was 3.1%, and there was no mortality. @*Conclusion@#TSA can be considered a safe and potentially curative treatment for selective microprolactinomas as an alternative to treatment with a long-term DA.

3.
Experimental Neurobiology ; : 120-143, 2021.
Article in English | WPRIM | ID: wpr-890648

ABSTRACT

Central neurocytoma (CN) has been known as a benign neuronal tumor. In rare cases, CN undergoes malignant transformation to glioblastomas (GBM). Here we examined its cellular origin by characterizing differentiation potential and gene expression of CN-spheroids. First, we demonstrate that both CN tissue and cultured primary cells recapitulate the hierarchal cellular composition of subventricular zone (SVZ), which is comprised of neural stem cells (NSCs), transit amplifying progenitors (TAPs), and neuroblasts. We then derived spheroids from CN which displayed EGFR+/ MASH+ TAP and BLBP+ radial glial cell (RGC) characteristic, and mitotic neurogenesis and gliogenesis by single spheroids were observed with cycling multipotential cells. CN-spheroids expressed increased levels of pluripotency and tumor stem cell genes such as KLF4 and TPD5L1, when compared to their differentiated cells and human NSCs. Importantly, Gene Set Enrichment Analysis showed that gene sets of GBM-Spheroids, EGFR Signaling, and Packaging of Telomere Ends are enriched in CN-spheroids in comparison with their differentiated cells. We speculate that CN tumor stem cells have TAP and RGC characteristics, and upregulation of EGFR signaling as well as downregulation of eph-ephrin signaling have critical roles in tumorigenesis of CN. And their ephemeral nature of TAPs destined to neuroblasts, might reflect benign nature of CN.

4.
Article in English | WPRIM | ID: wpr-899851

ABSTRACT

Background@#Although long-term dopamine agonist (DA) therapy is recommended as a first-line treatment for prolactinoma, some patients may prefer surgical treatment because of the potential adverse effects of long-term medication, or the desire to become pregnant. This study aimed to determine whether surgical treatment of prolactinomas could be an alternative to DA therapy. @*Methods@#In this retrospective study, 96 consecutive patients (74 female, 22 male) underwent primary pituitary surgery without long-term DA treatment for prolactinomas at a single institution from 1990 to 2010. All patients underwent primary surgical treatment in the microscopic transsphenoidal approach (TSA). @*Results@#The median age and median follow-up period were 31 (16–73) years and 139.1 (12.2–319.6) months, respectively. An initial overall remission was accomplished in 47.9% (46 of 96 patients, 33 macroadenomas, and 13 microadenomas) of patients. DA dose reduction was achieved in all patients after TSA. A better remission rate was independently predicted by lower diagnostic prolactin levels and by a greater extent of surgical resection. Overall remission at the last follow-up was 33.3%, and the overall recurrence rate was 30.4%. The permanent complication rate was 3.1%, and there was no mortality. @*Conclusion@#TSA can be considered a safe and potentially curative treatment for selective microprolactinomas as an alternative to treatment with a long-term DA.

5.
Article in English | WPRIM | ID: wpr-915590

ABSTRACT

Objective@#: People are living longer and the elderly population continues to increase. The incidence of degenerative spinal diseases (DSDs) in the elderly population is quite high. Therefore, we are facing more cases of DSD and offering more surgical solutions in geriatric patients. Understanding the significance and association of frailty and central sarcopenia as risk factors for spinal surgery in elderly patients will be helpful in improving surgical outcomes. We conducted a retrospective cohort analysis of prospectively collected data to assess the impact of preoperative central sarcopenia, frailty, and comorbidity on surgical outcome in elderly patients with DSD. @*Methods@#: We conducted a retrospective analysis of patients who underwent elective spinal surgery performed from January 1, 2019 to September 30, 2020 at our hospital. We included patients aged 65 and over who underwent surgery on the thoracic or lumbar spine and were diagnosed as DSD. Central sarcopenia was measured by the 50th percentile of psoas : L4 vertebral index (PLVI) using the cross-sectional area of the psoas muscle. We used the Korean version of the fatigue, resistance, ambulation, illnesses, and loss of weight (K-FRAIL) scale to measure frailty. Comorbidity was confirmed and scored using the Charlson Comorbidity Index (CCI). As a tool for measuring surgical outcome, we used the Clavien-Dindo (CD) classification for postoperative complications and the length of stay (LOS). @*Results@#: This study included 85 patients (35 males and 50 females). The mean age was 74.05±6.47 years. Using the K-FRAIL scale, four patients were scored as robust, 44 patients were pre-frail and 37 patients were frail. The mean PLVI was 0.61±0.19. According to the CD classification, 50 patients were classified as grade 1, 19 as grade 2, and four as grade 4. The mean LOS was 12.35±8.17 days. Multivariate stepwise regression analysis showed that postoperative complication was significantly associated with surgical invasiveness and K-FRAIL scale. LOS was significantly associated with surgical invasiveness and CCI. K-FRAIL scale showed a significant correlation with CCI and PLVI. @*Conclusion@#: The present study demonstrates that frailty, comorbidity, and surgical invasiveness are important risk factors for postoperative complications and LOS in elderly patients with DSD. Preoperative recognition of these factors may be useful for perioperative optimization, risk stratification, and patient counseling.

6.
Article | WPRIM | ID: wpr-831700

ABSTRACT

Background@#Two primary treatment methods are used for ruptured cerebral aneurysms, surgical clipping and endovascular coiling. In recent decades, endovascular coiling has shown remarkable progress compared to surgical clipping, along with technological developments. The aim of this study was to investigate the recent trends in treatments for ruptured cerebral aneurysms in Korea. @*Methods@#The data were obtained from the National Health Insurance database. We evaluated the trends in endovascular coiling and surgical clipping for ruptured aneurysms for the period 2000–2017. We obtained the number of prescriptions with International Classification of Diseases, 9th Revision, clinical modification codes related to nontraumatic subarachnoid hemorrhage and prescription codes S4641/4642 for surgical clipping and M1661/1662 for endovascular coiling. The medical expenses for each prescription were also obtained. The primary outcomes included the cumulative number of patients, patient rates per 100,000 people, and the correlation between patient rates and the percentage of the population in each age group. @*Results@#In the case of surgical clipping, there were no increasing or decreasing trends in the cumulative number of patients when the population/age group was ignored. When examining the trends in patient rates per 100,000 population at each year in male, there was no increasing or decreasing trend in the number of surgical clippings between the age groups, in spite of a decreasing tendency in the number of surgical clipping in male in their 40s and older than 60. In females, the surgical clipping rates tended to decrease only in patients older than 60 years, but there was no tendency to increase or decrease in the other ages. In contrast, the cumulative number of patients who underwent endovascular coiling for ruptured cerebral aneurysms increased year by year regardless of the population/age group. In both male and female, there was no increasing or decreasing trend only in the group aged 40 or younger and there was an increasing tendency in the rest of the age groups. In the trend of medical expenses, both the cost of surgical clipping and endovascular coiling showed increases. Specifically, the medical expense trend in endovascular coiling increased more rapidly than that for surgical clipping. @*Conclusion@#There was a significant increase in the proportion of patients with ruptured aneurysms undergoing endovascular coiling between 2010 and 2017, whereas the use of surgical clipping decreased. The endovascular coiling was significantly increased in all age groups and surgical clipping was decreased in all age groups, especially in patients under 50 years of age.

7.
Article in English | WPRIM | ID: wpr-833486

ABSTRACT

Objective@#: Spinal degeneration is a progressive disease, worsening over time. Lumbar degenerative disease (LDD) is a major spinal disease in elderly patients. Surgical treatment is considered for medically intractable patients with LDD and reoperation after primary surgery is not uncommon. The surgical outcome is occasionally unpredictable because of comorbidities. In the present study, the relationship between comorbidities and the incidence of reoperation for LDD over time was determined. @*Methods@#: The claims data of the health insurance national database were used to identify a cohort of patients who underwent spinal surgery for LDD in 2009. The patients were followed up until 2016. Medical comorbidity was assessed according to the Charlson comorbidity index (CCI). Cox proportional hazard regression modeling was used to identify significant differences in sex, surgery, age, causative disease, and comorbidity. @*Results@#: The study cohort included 78241 patients; 10328 patients (13.2%) underwent reoperation during the observation period. The reoperation rate was statistically higher (p<0.01) in males, patients 55–74 years and 65–74 years of age, and patients with decompression or discectomy. Significant association was found between increasing reoperation rate and CCI score (p<0.01). Based on multivariate analysis of comorbidities, the significantly higher reoperation rates were observed in patients with peripheral vascular disease, pulmonary lung disease, peptic ulcer, diabetes, and diabetes complications (p<0.01). @*Conclusion@#: The study results indicate the reoperation rate for LDD is associated with patient comorbidities. The comorbidities identified in this study could be helpful in future LDD studies.

8.
Article in English | WPRIM | ID: wpr-765163

ABSTRACT

BACKGROUND: Recently, a new generation of gamma knife radiosurgery (GKRS) equipped with a frameless immobilization system has encouraged the use of fractionated GKRS as an increasingly favorable treatment option. We investigated the preliminary outcome of efficacy and toxicity associated with frameless fractionated gamma knife radiosurgery (FF GKRS) for the treatment of large metastatic brain tumors. METHODS: Fifteen patients with 17 lesions were treated using FF GKRS and included in this study, because of the large tumor size of more than 10 cm3. FF GKRS was performed based on a thermoplastic mask system for 3 to 5 consecutive days. RESULTS: The mean duration of clinical follow-up was 12 months (range, 4–24), and the local control rate was 100%. Tumor volume decreased in 13 lesions (76.5%), and remained stable in 4 lesions (23.5%). One patient was classified as new lesion development because of the occurrence of leptomeningeal seeding regardless of the tumor volume change. Compared with the initial volume at the time of FF GKRS, tumor volume change at the last follow-up was 62.32% ± 29.80%. Cumulative survival rate at 12 months was 93.3% ± 6.4%. One patient died during the follow-up period because of the progression of the primary disease. No patient showed radiation necrosis on the follow-up images. CONCLUSION: Daily FF GKRS by gamma knife ICON™ revealed satisfactory tumor control rate and low morbidity, despite the short follow-up period. Further prospective studies and a longer follow-up of a large cohort of patients diagnosed with brain metastases are required to elucidate the effect of FF GKRS in brain metastases.


Subject(s)
Brain Neoplasms , Brain , Cohort Studies , Follow-Up Studies , Humans , Immobilization , Masks , Necrosis , Neoplasm Metastasis , Prospective Studies , Radiosurgery , Survival Rate , Tumor Burden
9.
Article in English | WPRIM | ID: wpr-759993

ABSTRACT

We report 3 cases of arachnoid cysts (ACs) that completely disappeared after burr hole drainage, without cyst fenestration into the subarachnoid space or cystoperitoneal shunt. The first patient was a 21-year-old female with an AC of the right cerebral convexity, found incidentally. After endoscopic AC fenestration was performed, the patient complained of persistent headache. Two-month postoperative brain imaging revealed reaccumulated AC and associated multi-stage subdural hematoma. Burr hole drainage was performed to resolve the chronic subdural hematoma (CSDH). Three months later, brain computed tomography showed that the CSDH and the AC had disappeared. The second patient was an 11-year-old male who had a history of trauma 1 month prior to presentation at the clinic. Brain magnetic resonance imaging revealed an AC in the left sylvian fissure with CSDH. We performed burr hole drainage to treat the CSDH first. Subsequently, the AC as well as the CSDH disappeared. The third case was an AC of the right parietal convexity, found incidentally. Only burr hole drainage was performed, following which, the AC disappeared. This case series shows that an AC can disappear naturally after rupture into the subdural space by trauma or the burr hole procedure.


Subject(s)
Arachnoid Cysts , Arachnoid , Brain , Child , Drainage , Female , Headache , Hematoma, Subdural , Hematoma, Subdural, Chronic , Humans , Magnetic Resonance Imaging , Male , Neuroimaging , Rabeprazole , Rupture , Subarachnoid Space , Subdural Space , Trephining , Young Adult
10.
Article in English | WPRIM | ID: wpr-788648

ABSTRACT

OBJECTIVE: In respect of the health and safety of the public, universal access to health care is an issue of the greatest importance. The geographic distribution of doctors is one of the important factors contributing to access to health care. The aim of this study is to assess the imbalances in the geographic distribution of neurosurgeons across Korea.METHODS: Population data was obtained from the National Statistical Office. We classified geographic groups into 7 metropolitan cities, 78 non-metropolitan cities, and 77 rural areas. The number of doctors and neurosurgeons per 100000 populations in each county unit was calculated using the total number of doctors and neurosurgeons at the country level from 2009 to 2015. The density levels of neurosurgeon and doctor were calculated and depicted in maps.RESULTS: Between 2009 and 2015, the number of neurosurgeons increased from 2002 to 2557, and the ratio of neurosurgeons per 100000 populations increased from 4.02 to 4.96. The number of neurosurgeons per 100000 populations was highest in metropolitan cities and lowest in rural areas from 2009 to 2015. A comparison of the geographic distribution of neurosurgeons in 2009 and 2015 showed an increase in the regional gap. The neurosurgeon density was affected by country unit characteristics (p=0.000).CONCLUSION: Distribution of neurosurgeons throughout Korea is uneven. Neurosurgeons are being increasingly concentrated in a limited number of metropolitan cities. This phenomenon will need to be accounted when planning for a supply of neurosurgeons, allocation of resources and manpower, and the provision of regional neurosurgical services.


Subject(s)
Geographic Mapping , Health Workforce , Health Services Accessibility , Hospital Distribution Systems , Korea , Neurosurgeons , Neurosurgery , Resource Allocation
11.
Article in English | WPRIM | ID: wpr-765218

ABSTRACT

OBJECTIVE: In respect of the health and safety of the public, universal access to health care is an issue of the greatest importance. The geographic distribution of doctors is one of the important factors contributing to access to health care. The aim of this study is to assess the imbalances in the geographic distribution of neurosurgeons across Korea. METHODS: Population data was obtained from the National Statistical Office. We classified geographic groups into 7 metropolitan cities, 78 non-metropolitan cities, and 77 rural areas. The number of doctors and neurosurgeons per 100000 populations in each county unit was calculated using the total number of doctors and neurosurgeons at the country level from 2009 to 2015. The density levels of neurosurgeon and doctor were calculated and depicted in maps. RESULTS: Between 2009 and 2015, the number of neurosurgeons increased from 2002 to 2557, and the ratio of neurosurgeons per 100000 populations increased from 4.02 to 4.96. The number of neurosurgeons per 100000 populations was highest in metropolitan cities and lowest in rural areas from 2009 to 2015. A comparison of the geographic distribution of neurosurgeons in 2009 and 2015 showed an increase in the regional gap. The neurosurgeon density was affected by country unit characteristics (p=0.000). CONCLUSION: Distribution of neurosurgeons throughout Korea is uneven. Neurosurgeons are being increasingly concentrated in a limited number of metropolitan cities. This phenomenon will need to be accounted when planning for a supply of neurosurgeons, allocation of resources and manpower, and the provision of regional neurosurgical services.


Subject(s)
Geographic Mapping , Health Workforce , Health Services Accessibility , Hospital Distribution Systems , Korea , Neurosurgeons , Neurosurgery , Resource Allocation
12.
Article in English | WPRIM | ID: wpr-713248

ABSTRACT

Spontaneous chronic subdural hematoma (SDH) is a rare condition that could develop in association with hematologic disease. A 66-year-old male developed a chronic SDH as an initial manifestation of chronic myelomonocytic leukemia (CMML). He experienced recurrent chronic subdural hemorrhage and newly developed intracerebral hemorrhage. Considering the scheduled long-term chemotherapy, bilateral middle meningeal artery (MMA) embolization was performed to prevent recurrence of subdural hemorrhage. Although pancytopenia occurred during the 7 months' follow-up period, residual chronic subdural hemorrhage was absorbed without recurrence. To our best knowledge, this is the first report of CMML with spontaneous chronic SDH. MMA embolization is potentially a useful and safe treatment option in the challenging clinical situations with underlying pathologies.


Subject(s)
Aged , Cerebral Hemorrhage , Drug Therapy , Follow-Up Studies , Hematologic Diseases , Hematoma, Subdural , Hematoma, Subdural, Chronic , Humans , Leukemia , Leukemia, Myelomonocytic, Chronic , Male , Meningeal Arteries , Pancytopenia , Pathology , Recurrence
13.
Experimental Neurobiology ; : 245-255, 2018.
Article in English | WPRIM | ID: wpr-714903

ABSTRACT

We present our experience on the hypofractionated Gamma Knife radiosurgery (FGKS) for large skull base meningioma as an initial treatment. We retrospectively reviewed 23 patients with large skull base meningioma ≥10 cm³ who underwent FGKS as the initial treatment option. The mean volume of tumors prior to radiosurgery was 21.2±15.63 cm³ (range, 10.09~71.42). The median total margin dose and marginal dose per fraction were 18 Gy (range, 15~20) and 6 Gy (range, 5~6), respectively. Patients underwent three or four fractionations in consecutive days with the same Leksell® frame. The mean follow-up duration was 38 months (range, 17~78). There was no mortality. At the last follow-up, the tumor volume was stationary in 15 patients (65.2%) and had decreased in 8 patients (34.8%). Six patients who had cranial neuropathy at the time of FGKS showed improvement at the last clinical follow-up. Following FGKS, 4 patients (17%) had new cranial neuropathy. The trigeminal neuropathy was the most common and all were transient. The mean Karnofsky Performance Status score at pre-FGKS and the last clinical follow-up was 97.0±10.4 points (median, 100) and 98.6±6.9 (median, 100) points, respectively. FGKS has showed satisfactory tumor control with functional preservation for large skull base meningiomas. Further prospective studies of large cohorts with long term follow-up are required to clarify the efficacy in the tumor control and functional outcome as well as radiation toxicity.


Subject(s)
Cohort Studies , Cranial Nerve Diseases , Radiation Dose Hypofractionation , Follow-Up Studies , Humans , Karnofsky Performance Status , Meningioma , Mortality , Prospective Studies , Radiosurgery , Retrospective Studies , Skull Base , Skull , Trigeminal Nerve Diseases , Tumor Burden
14.
Article in English | WPRIM | ID: wpr-714858

ABSTRACT

OBJECTIVE: Minimally invasive techniques such as stereotactic aspiration have been regarded as promising alternative methods to replace craniotomy in the treatment of intracerebral hemorrhage (ICH). The aim of this study was to identify the optimal timing of stereotactic aspiration and analyze the factors affecting the clinical outcome. MATERIALS AND METHODS: This retrospective study included 81 patients who underwent stereotactic aspiration for spontaneous supratentorial ICH at single institution. Volume of hematoma was calculated based on computed tomography scan at admission, just before aspiration, immediately after aspiration, and after continuous drainage. The neurologic outcome was compared with Glasgow outcome scale (GOS) score. RESULTS: The mean volume ratio of residual hematoma was 59.5% and 17.6% immediately after aspiration and after continuous drainage for an average of 2.3 days, respectively. Delayed aspiration group showed significantly lower residual volume ratio immediately after aspiration. However, there was no significant difference in the residual volume ratio after continuous drainage. The favorable outcome of 1-month GOS 4 or 5 was significantly better in the group with delayed aspiration after more than 7 days (p = 0.029), despite no significant difference in postoperative 6-months GOS score. A factor which has significant correlation with postoperative 6-months favorable outcome was the final hematoma volume ratio after drainage (p = 0.028). CONCLUSION: There is no difference in final residual volume of hematoma or 6-months neurologic outcome according to the surgical timing of hematoma aspiration. The only factor affecting the postoperative 6-months


Subject(s)
Cerebral Hemorrhage , Craniotomy , Drainage , Glasgow Outcome Scale , Hematoma , Humans , Minimally Invasive Surgical Procedures , Residual Volume , Retrospective Studies , Stereotaxic Techniques
15.
Article in English | WPRIM | ID: wpr-104366

ABSTRACT

Internal globus pallidus (GPi) deep brain stimulation (DBS) has been widely accepted as an effective treatment modality of medically refractory dystonia. However, there have been few studies regarding the safety issue of pregnancy and childbirth related with DBS. This report describes a female patient who was pregnant and delivered a baby after GPi DBS surgery. A 33-year-old female patient with acquired generalized dystonia underwent bilateral GPi DBS implantation. She obtained considerable improvement in both movement and disability after DBS implantation. Four years later, she was pregnant and the obstetricians consulted us about the safety of the delivery. At 38-weeks into pregnancy, a scheduled caesarian section was carried out under general anesthesia. After induction using thiopental and succinylcholine, intubation was done quickly, followed by DBS turn off. For hemostasis, only bipolar electrocautery was used. Before awakening from the anesthesia, DBS was turned on as the same parameters previously adjusted. After delivery, she could feed her baby by herself, because the dystonia of left upper extremity and hand was improved. Until now, she has been showing continual improvement and being good at housework, carrying for children, with no trouble in daily life. This observation indicates that the patients who underwent DBS could safely be pregnant and deliver a baby.


Subject(s)
Adult , Anesthesia , Anesthesia, General , Child , Deep Brain Stimulation , Dystonia , Electrocoagulation , Female , Globus Pallidus , Hand , Hemostasis , Household Work , Humans , Intubation , Parturition , Pregnancy , Succinylcholine , Thiopental , Upper Extremity
16.
Article in English | WPRIM | ID: wpr-30376

ABSTRACT

Stem cell therapies are administered during the acute phase of stroke to preserve the penumbral tissues from ischemic injury. However, the effect of repeated cell therapy during the acute phase remains unclear. In this study, we investigated and compared the functional outcome of single (two days post-injury) and repeated (two and nine days post-injury) treatment with human umbilical cord derived mesenchymal stem cells (hUCB-MSCs) after middle cerebral artery occlusion (MCAO). The rotarod and limb placement tests were utilized to investigate functional outcomes, while infarct volume and tissue damage were measured by immunofluorescent staining for neovascularization, neurogenesis, apoptosis, and inflammation in the penumbral zones. We observed notable motor dysfunction and a significant decrease in infarcted brain volume, as well as increases in neurons and vessels in both single and repeated hUCB-MSC treatments compared to the control group. Interestingly, repeated administration of hUCB-MSCs was not found to elicit additional or synergistic improvements over monotherapy. This study suggests that a clearer understanding of the therapeutic window after stroke will facilitate the development of more efficient treatment protocols in the clinical application of stem cell therapy.


Subject(s)
Animals , Apoptosis , Brain , Brain Ischemia , Cell- and Tissue-Based Therapy , Clinical Protocols , Extremities , Humans , Infarction, Middle Cerebral Artery , Inflammation , Ischemia , Mesenchymal Stem Cells , Neurogenesis , Neurons , Rats , Stem Cells , Stroke , Umbilical Cord
17.
Experimental Neurobiology ; : 295-306, 2017.
Article in English | WPRIM | ID: wpr-18843

ABSTRACT

Glioblastoma multiforme (GBM) is the most common and aggressive form of brain tumors. GBMs, like other tumors, rely relatively less on mitochondrial oxidative phosphorylation (OXPHOS) and utilize more aerobic glycolysis, and this metabolic shift becomes augmented under hypoxia. In the present study, we investigated the physiological significance of altered glucose metabolism and hypoxic adaptation in the GBM cell line U251 and two newly established primary GBMs (GBM28 and GBM37). We found that these three GBMs exhibited differential growth rates under hypoxia compared to those under normoxia. Under normoxia, the basal expressions of HIF1α and the glycolysis-associated genes, PDK1, PDK3, and GLUT1, were relatively low in U251 and GBM28, while their basal expressions were high in GBM37. Under hypoxia, the expressions of these genes were enhanced further in all three GBMs. Treatment with dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), induced cell death in GBM28 and GBM37 maintained under normoxia, whereas DCA effects disappeared under hypoxia, suggesting that hypoxic adaptation dominated DCA effects in these GBMs. In contrast, the inhibition of HIF1α with chrysin suppressed the expression of PDK1, PDK3, and GLUT1 and markedly promoted cell death of all GBMs under both normoxia and hypoxia. Interestingly, however, GBMs treated with chrysin under hypoxia still sustained higher viability than those under normoxia, and chrysin and DCA co-treatment was unable to eliminate this hypoxia-dependent resistance. Together, these results suggest that hypoxic adaptation is critical for maintaining viability of GBMs, and targeting hypoxic adaptation can be an important treatment option for GBMs.


Subject(s)
Hypoxia , Brain Neoplasms , Cell Death , Cell Line , Dichloroacetic Acid , Glioblastoma , Glucose , Glycolysis , Metabolism , Oxidative Phosphorylation , Oxidoreductases , Phosphotransferases , Pyruvic Acid
18.
Article in English | WPRIM | ID: wpr-169714

ABSTRACT

Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders characterized by a deficit in social behaviors and nonverbal interactions such as reduced eye contact, facial expression, and body gestures in the first 3 years of life. It is not a single disorder, and it is broadly considered to be a multi-factorial disorder resulting from genetic and non-genetic risk factors and their interaction. Genetic studies of ASD have identified mutations that interfere with typical neurodevelopment in utero through childhood. These complexes of genes have been involved in synaptogenesis and axon motility. Recent developments in neuroimaging studies have provided many important insights into the pathological changes that occur in the brain of patients with ASD in vivo. Especially, the role of amygdala, a major component of the limbic system and the affective loop of the cortico-striatothalamo-cortical circuit, in cognition and ASD has been proved in numerous neuropathological and neuroimaging studies. Besides the amygdala, the nucleus accumbens is also considered as the key structure which is related with the social reward response in ASD. Although educational and behavioral treatments have been the mainstay of the management of ASD, pharmacological and interventional treatments have also shown some benefit in subjects with ASD. Also, there have been reports about few patients who experienced improvement after deep brain stimulation, one of the interventional treatments. The key architecture of ASD development which could be a target for treatment is still an uncharted territory. Further work is needed to broaden the horizons on the understanding of ASD.


Subject(s)
Amygdala , Autistic Disorder , Axons , Brain , Child , Autism Spectrum Disorder , Cognition , Deep Brain Stimulation , Facial Expression , Gestures , Humans , Limbic System , Neurobiology , Neuroimaging , Nucleus Accumbens , Reward , Risk Factors , Social Behavior
19.
Experimental Neurobiology ; : 93-101, 2016.
Article in English | WPRIM | ID: wpr-137232

ABSTRACT

An 18-year-old left-handed male harbored intractable medial temporal lobe epilepsy (MTLE) underwent fractionated gamma knife surgery (GKS) instead of open surgery, considering the mental retardation and diffuse cerebral dysfunction. GKS treatment parameters were: target volume, 8.8 cm3; total marginal dose, 24 Gy in 3 fractionations at the 50% isodose line. The patient has been free from seizures since 9 months after GKS, with notable improvement in cognitive outcome. Fractionated GKS could be considered as a safe tool for seizure control and neuropsychological improvement in patients with MTLE.


Subject(s)
Adolescent , Epilepsy , Epilepsy, Temporal Lobe , Humans , Intellectual Disability , Male , Radiosurgery , Seizures , Stereotaxic Techniques , Temporal Lobe
20.
Experimental Neurobiology ; : 93-101, 2016.
Article in English | WPRIM | ID: wpr-137229

ABSTRACT

An 18-year-old left-handed male harbored intractable medial temporal lobe epilepsy (MTLE) underwent fractionated gamma knife surgery (GKS) instead of open surgery, considering the mental retardation and diffuse cerebral dysfunction. GKS treatment parameters were: target volume, 8.8 cm3; total marginal dose, 24 Gy in 3 fractionations at the 50% isodose line. The patient has been free from seizures since 9 months after GKS, with notable improvement in cognitive outcome. Fractionated GKS could be considered as a safe tool for seizure control and neuropsychological improvement in patients with MTLE.


Subject(s)
Adolescent , Epilepsy , Epilepsy, Temporal Lobe , Humans , Intellectual Disability , Male , Radiosurgery , Seizures , Stereotaxic Techniques , Temporal Lobe
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