Sung-Rae Cho

Yonsei University Hospital, Sŏul, Seoul, South Korea

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Publications (27)78.75 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Recently, cell-based therapy has been highlighted as an alternative to treating ischemic brain damage in stroke patients. The present study addresses the therapeutic potential of polysialic acid-neural cell adhesion molecule (PSA-NCAM)-positive neural precursor cells (NPC(PSA-NCAM+)) derived from human embryonic stem cells (hESCs) in a rat stroke model with permanent middle cerebral artery occlusion. Data showed that rats transplanted with NPC(PSA-NCAM+) are superior to those treated with phosphate buffered saline (PBS) or mesenchymal stem cells (MSCs) in behavioral performance throughout time points. In order to investigate its underlying events, immunohistochemical analysis was performed on rat ischemic brains treated with PBS, MSCs, and NPC(PSA-NCAM+). Unlike MSCs, NPC(PSA-NCAM+) demonstrated a potent immunoreactivity against human specific nuclei, doublecortin, and Tuj1 at day 26 post-transplantation, implying their survival, differentiation, and integration in the host brain. Significantly, NPC(PSA-NCAM+) evidently lowered the positivity of microglial ED-1 and astrocytic GFAP, suggesting a suppression of adverse glial activation in the host brain. In addition, NPC(PSA-NCAM+) elevated α-SMA(+) immunoreactivity and the expression of angiopoietin-1 indicating angiogenic stimulation in the host brain. Taken together, the current data demonstrate that transplanted NPC(PSA-NCAM+) preserve brain tissue with reduced infarct size and improve behavioral performance through actions encompassing anti-reactive glial activation and pro-angiogenic activity in a rat stroke model. In conclusion, the present findings support the potentiality of NPC(PSA-NCAM+) as the promising source in the development of cell-based therapy for neurological diseases including ischemic stroke.
    Stem cell reviews. 06/2014;
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    ABSTRACT: Hemophilia A, one of the most common genetic bleeding disorders, is caused by various mutations in the blood coagulation factor VIII (F8) gene. Among the genotypes that result in hemophilia A, two different types of chromosomal inversions that involve a portion of the F8 gene are most frequent, accounting for almost half of all severe hemophilia A cases. In this study, we used a transcription activator-like effector nuclease (TALEN) pair to invert a 140-kbp chromosomal segment that spans the portion of the F8 gene in human induced pluripotent stem cells (iPSCs) to create a hemophilia A model cell line. In addition, we reverted the inverted segment back to its normal orientation in the hemophilia model iPSCs using the same TALEN pair. Importantly, we detected the F8 mRNA in cells derived from the reverted iPSCs lines, but not in those derived from the clones with the inverted segment. Thus, we showed that TALENs can be used both for creating disease models associated with chromosomal rearrangements in iPSCs and for correcting genetic defects caused by chromosomal inversions. This strategy provides an iPSC-based novel therapeutic option for the treatment of hemophilia A and other genetic diseases caused by chromosomal inversions.
    Proceedings of the National Academy of Sciences of the United States of America. 06/2014;
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    ABSTRACT: To investigate the effect of deep brain stimulation (DBS) on reducing dystonia and disability in adults with cerebral palsy (CP) and to compare the therapeutic outcomes between primary dystonia patients and CP patients over two years after bilateral pallidal DBS.
    Annals of rehabilitation medicine. 04/2014; 38(2):209-17.
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    ABSTRACT: Erythropoietin (EPO) and granulocyte colonystimulating factor (G-CSF) are likely to play broad roles in the brain. We investigated the effects of combination therapy with EPO and G-CSF in hypoxic-ischemic brain injury during the acute, subacute, and chronic phases. A total of 79 C57BL/6 mice with hypoxic-ischemic brain injury were randomly assigned acute (days 1-5), subacute (days 11-15) and chronic (days 28-32) groups. All of them were treated with G-CSF (250 μg/kg) and EPO (5 000 U/kg) or saline daily for 5 consecutive days. Behavioral assessments and immunohistochemistry for angiogenesis, neurogenesis, and astrogliosis were performed with an 8-week follow-up. Hypoxia-inducible factor-1 (HIF-1) was also measured by Western blot analysis. The results showed that the combination therapy with EPO and G-CSF in the acute phase significantly improved rotarod performance and forelimb-use symmetry compared to the other groups, while subacute EPO and G-CSF therapy exhibited a modest improvement compared with the chronic saline controls. The acute treatment significantly increased the density of CD31(+) (PECAM-1) and α-smooth muscle actin(+) vessels in the frontal cortex and striatum, increased BrdU(+)/PSANCAM(+) neurogenesis in the subventricular zone, and decreased astroglial density in the striatum. Furthermore, acute treatment significantly increased the HIF-1 expression in the cytosol and nucleus, whereas chronic treatment did not change the HIF-1 expression, consistent with the behavioral outcomes. These results indicate that the induction of HIF-1 expression by combination therapy with EPO and G-CSF synergistically enhances not only behavioral function but also neurogenesis and angiogenesis while decreasing the astroglial response in a timedependent manner.
    Neuroscience Bulletin 01/2014; · 1.37 Impact Factor
  • Hyun Ju Chong, Sung-Rae Cho, Soo Ji Kim
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    ABSTRACT: As a sequential, programmed movement of fingers, keyboard playing is a promising technique for inducing execution and a high level of coordination during finger movements. Also, keyboard playing can be physically and emotionally rewarding for adolescents in rehabilitation settings and thereby motivate continued involvement in treatment. The purpose of this study is to evaluate the effects of keyboard playing using Musical Instrument Digital Interface (MIDI) on finger movement for adolescents with brain damage. Eight adolescents with brain damage, ages 9 to 18 years (M = 13 years, SD = 2.78), in physical rehabilitation settings participated in this study. Measurements included MIDI keyboard playing for pressing force of the fingers and hand function tests (Grip and Pinch Power Test, Box and Block Test of Manual Dexterity [BBT], and the Jebsen Taylor Hand Function Test). Results showed increased velocity of all fingers on the MIDI-based test, and statistical significance was found in the velocity of F2 (index finger), F3 (middle finger), and F5 (little finger) between pre- and post-training tests. Correlation analysis between the pressing force of the finger and hand function tests showed a strong positive correlation between the measure of grip power and the pressing force of F2 and F5 on the Grip and Pinch Strength Test. All fingers showed strong correlation between MIDI results and BBT. For the Jebsen Taylor Hand Function Test, only the moving light objects task at post-training yielded strong correlation with MIDI results of all fingers. The results support using keyboard playing for hand rehabilitation, especially in the pressing force of individual finger sequential movements. Further investigation is needed to define the feasibility of the MIDI program for valid hand rehabilitation for people with brain damage.
    Neurorehabilitation 11/2013; · 1.42 Impact Factor
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    ABSTRACT: Repetitive transcranial magnetic stimulation (rTMS) is used to treat neurological diseases such as stroke and Parkinson's disease (PD). Although rTMS has been used clinically, its underlying therapeutic mechanism remains unclear. The objective of the present study was to clarify the neuroprotective effect and therapeutic mechanism of rTMS in an animal model of PD. Adult Sprague-Dawley rats were unilaterally injected with 6-hydroxydopamine (6-OHDA) into the right striatum. Rats with PD were then treated with rTMS (circular coil, 10Hz, 100% of motor threshold, 20min/day) daily for 4 weeks. Behavioral assessments such as amphetamine-induced rotational test and treadmill locomotion test were performed, and the dopaminergic (DA) neurons of substantia nigra pas compacta (SNc) were histologically examined. Expression of neurotrophic/growth factors was also investigated by multiplex ELISA and western blotting analysis 4 weeks after rTMS application. Among the results, the number of amphetamine-induced rotations was significantly lower in the rTMS group than in the control group at 4 weeks post-treatment. Treadmill locomotion was also significantly improved in the rTMS-treated rats. Tyrosine hydroxylase-positive DA neurons and DA fibers in rTMS group rats were greater than those in untreated group in both ipsilateral SNc and striatum, respectively. The expression levels of brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, platelet-derived growth factor, and vascular endothelial growth factor were elevated in both the 6-OHDA-injected hemisphere and the SNc of the rTMS-treated rats. In conclusion, rTMS treatment improved motor functions and survival of DA neurons, suggesting that the neuroprotective effect of rTMS treatment might be induced by upregulation of neurotrophic/growth factors in the PD animal model.
    Brain research 08/2013; · 2.46 Impact Factor
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    ABSTRACT: After spinal cord injury (SCI), functional and structural reorganization occurs at multiple levels of brain including motor cortex. However, the underlying mechanism still remains unclear. The current study was performed to investigate the alterations in the expression of the main regulators of neuronal development, survival and death, in the brain following thoracic contusive SCI in a mouse model. Eight-week-old female imprinting control region mice (n=60; 30-35 g) were used in this study. We analyzed the expression levels of regulators such as brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF) and histone deacetylase (HDAC) 1 in the brain following thoracic contusive SCI. The expression of BDNF levels were elevated significantly compared with control group at 2 weeks after injury (p<0.05). The expression of NGF levels were elevated at 2, 4 weeks compared with control group, but these difference were not significant (p>0.05). The GDNF levels were elevated at 2 week compared with control group, but these differences were not significant (p>0.05). The difference of HDAC1 levels were not significant at 2, 4 and 8 weeks compared with control group (p>0.05). These results demonstrate that the upregulation of BDNF may play on important role in brain reorganization after SCI.
    Journal of Korean Neurosurgical Society 06/2013; 53(6):337-41. · 0.56 Impact Factor
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    ABSTRACT: BACKGROUND: . Housing animals in an enriched environment (EE) enhances behavioral function. However, the mechanism underlying this EE-mediated functional improvement and the resultant changes in gene expression have yet to be elucidated. OBJECTIVES: . We attempted to investigate the underlying mechanisms associated with long-term exposure to an EE by evaluating gene expression patterns. METHODS: . We housed 6-week-old CD-1 (ICR) mice in standard cages or an EE comprising a running wheel, novel objects, and social interaction for 2 months. Motor and cognitive performances were evaluated using the rotarod test and passive avoidance test, and gene expression profile was investigated in the cerebral hemispheres using microarray and gene set enrichment analysis (GSEA). RESULTS: . In behavioral assessment, an EE significantly enhanced rotarod performance and short-term working memory. Microarray analysis revealed that genes associated with neuronal activity were significantly altered by an EE. GSEA showed that genes involved in synaptic transmission and postsynaptic signal transduction were globally upregulated, whereas those associated with reuptake by presynaptic neurotransmitter transporters were downregulated. In particular, both microarray and GSEA demonstrated that EE exposure increased opioid signaling, acetylcholine release cycle, and postsynaptic neurotransmitter receptors but decreased Na(+)/Cl(-)-dependent neurotransmitter transporters, including dopamine transporter Slc6a3 in the brain. Western blotting confirmed that SLC6A3, DARPP32 (PPP1R1B), and P2RY12 were largely altered in a region-specific manner. CONCLUSION: . An EE enhanced motor and cognitive function through the alteration of synaptic activity-regulating genes, improving the efficient use of neurotransmitters and synaptic plasticity by the upregulation of genes associated with postsynaptic receptor activity and downregulation of presynaptic reuptake by neurotransmitter transporters.
    Neurorehabilitation and neural repair 04/2013; · 4.28 Impact Factor
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    ABSTRACT: We investigated the effects of environmental enrichment (EE) on the function of transplanted adipose stem cells (ASCs) and the combined effect of EE and ASC transplantation on neurobehavioral function in an animal model of chronic hypoxic-ischemic (HI) brain injury. HI brain damage was induced in 7-day-old mice by unilateral carotid artery ligation and exposure to hypoxia (8% O₂ for 90 min). At 6 weeks of age, the mice were randomly injected with either ASCs or PBS into the striatum and were randomly assigned to either EE or standard cages (SC), comprising ASC-EE (n=18), ASCSC (n=19), PBS-EE (n=12), PBS-SC (n=17), and untreated controls (n=23). Rotarod, forelimb-use asymmetry, and grip strength tests were performed to evaluate neurobehavioral function. The fate of transplanted cells and the levels of endogenous neurogenesis, astrocyte activation and paracrine factors were also measured. As a result, EE and ASC transplantation synergistically improved rotarod latency, forelimb-use asymmetry, and grip strength compared to those of the other groups. The number of engrafted ASCs and βIII-tubulin⁺ neurons derived from the transplanted ASCs were significantly higher in mice in EE than those in SC. EE and ASC transplantation also synergistically increasedBrdU⁺βIII-tubulin⁺ neurons, GFAP⁺ astrocytic density and fibroblast growth factor-2 (FGF2) level but not the level of CS-56⁺ glial scarring in the striatum. In conclusion, EE and ASC transplantation synergistically improved neurobehavioral functions. The underlying mechanisms of this synergism included enhanced repair processes such as higher engraftment of the transplanted ASCs, increased endogenous neurogenesis and astrocytic activation coupled with upregulation of FGF2.
    Cell Transplantation 02/2013; · 4.42 Impact Factor
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    ABSTRACT: The purpose of this study is to examine the effects of Therapeutic Instrument Music Performance (TIMP) for fine motor exercises in adults with cerebral palsy (CP). Individuals with CP (n = 5) received a total of twelve, 30-min TIMP sessions, two days per week for six to nine weeks. Pre- and post-Music Instrument Digital Interface (MIDI) data were used as a measure of hand function. Pre-velocity was significantly different from the normative data obtained from typical adults (n = 20); however, post-velocity did not yield significance, specifically in the second and fifth fingers, indicating improvement in hand function for the adults with cerebral palsy. The finding implies that TIMP using keyboard playing may effectively improve manual dexterity and velocity of finger movement. Based on these results, future program development of instrumental playing for adults with CP is called for to enhance both their independent living skills and quality of life.
    Journal of exercise rehabilitation. 01/2013; 9(4):420-425.
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    ABSTRACT: This study aimed to investigate the effects of enriched environment (EE) on promoting angiogenesis and neurobehavioral function in an animal model of chronic hypoxic-ischemic (HI) brain injury. HI brain damage was induced in seven day-old CD-1® mice by unilateral carotid artery ligation and exposure to hypoxia (8% O2 for 90 min). At six weeks of age, the mice were randomly assigned to either EE or standard cages (SC) for two months. Rotarod, forelimb-use asymmetry, and grip strength tests were performed to evaluate neurobehavioral function. In order to identify angiogenic growth factors regulated by EE, an array-based multiplex ELISA assay was used to measure the expression in frontal cortex, striatum, and cerebellum. Among the growth factors, the expression of fibroblast growth factor-2 (FGF-2) was confirmed using western blotting. Platelet endothelial cell adhesion molecule-1 (PECAM-1) and α-smooth muscle actin (α-SMA) were also evaluated using immunohistochemistry. As a result, mice exposed to EE showed significant improvements in rotarod and ladder walking performances compared to SC controls. The level of FGF-2 was significantly higher in the frontal cortex of EE mice at 8 weeks after treatment in multiplex ELISA and western blot. On the other hand, FGF-2 in the striatum significantly increased at 2 weeks after exposure to EE earlier than in the frontal cortex. Expression of activin A was similarly upregulated as FGF-2 expression pattern. Particularly, all animals treated with FGF-2 neutralizing antibody abolished the beneficial effect of EE on motor performance relative to mice not given anti-FGF-2. Immunohistochemistry showed that densities of α-SMA(+) and PECAM-1(+) cells in frontal cortex, striatum, and hippocampus were significantly increased following EE, suggesting the histological findings exhibit a similar pattern to the upregulation of FGF-2 in the brain. In conclusion, EE enhances endogenous angiogenesis and neurobehavioral functions mediated by upregulation of FGF-2 in chronic hypoxic-ischemic brain injury.
    PLoS ONE 01/2013; 8(9):e74405. · 3.73 Impact Factor
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    ABSTRACT: To clarify factors affecting bone mineral density (BMD) in adults with cerebral palsy (CP). Thirty-five patients with CP participated in this study. Demographic data including gender, age, body mass index (BMI), subtype according to neuromotor type and topographical distribution, ambulatory function, and functional independence measure (FIM) were investigated. The BMD of the lumbar spine and femur were measured using Dual-energy X-ray absorptiometry, and the factors affecting BMD were analyzed. The BMD had no significant association with factors such as gender, age, and subtype in adults with CP. However, BMI was significantly correlated with the BMD of lumbar spine and femur (p<0.05). The FIM score was also positively correlated with the BMD of femur (p<0.05). Moreover, CP patients with higher ambulatory function had significantly higher BMD of femur (p<0.05). These findings suggest that BMI and functional levels such as FIM and ambulatory function can affect BMD in adults with CP. The results might be used as basic data, suggesting the importance of treatment including weight bearing exercise and gait training in adults with CP.
    Annals of rehabilitation medicine. 12/2012; 36(6):770-5.
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    Jung Hwa Seo, Sung-Rae Cho
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    ABSTRACT: Stem cells are emerging as therapeutic candidates in a variety of diseases because of their multipotent capacities. Among these, mesenchymal stem cells (MSCs) derived from bone marrow, umbilical cord blood or adipose tissue, comprise a population of cells that exhibit extensive proliferative potential and retain the ability to differentiate into multiple tissue-specific lineage cells including osteoblasts, chondrocytes, and adipocytes. MSCs have also been shown to enhance neurological recovery, although the therapeutic effects seem to be derived from an indirect paracrine effect rather than direct cell replacement. MSCs secrete neurotrophic factors, promote endogenous neurogenesis and angiogenesis, encourage synaptic connection and remyelination of damaged axons, decrease apoptosis, and regulate inflammation primarily through paracrine actions. Accordingly, MSCs may prevail as a promising cell source for cell-based therapy in neurological diseases.
    Yonsei medical journal 11/2012; 53(6):1059-67. · 0.77 Impact Factor
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    ABSTRACT: Objective: We compared bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) with bilateral GPi DBS plus ventralis oralis (Vo) thalamotomy to analyze the effect of the combined Vo thalamotomy. Methods: Between March 2003 and December 2008, 10 patients underwent DBS and/or Vo thalamotomy for treatment of cerebral palsy in our institute of neurosurgery and rehabilitation medicine. Four patients received bilateral posteroventral GPi DBS as group I and 6 patients received GPi DBS plus unilateral thalamotomy as group II. Results: The movement and disability scores of group I improved by 32 and 14.3%, respectively, at the last follow-up compared with baseline. The movement and disability scores of group II improved by 31.5 and 0.18%. The BFMDRS-movement subscores of group II demonstrated statistically significant improvement in the contralateral arm compared to group I (p = 0.042). Body pain, vitality and mental health seemed to improve in group II, in terms of health-related quality of life. Conclusions: Contrary to our expectations, we were unable to demonstrate clear improvements in overall BFMDRS scores between group I and group II. However, movements of the contralateral upper extremities improved and health-related quality of life in group II showed satisfactory results.
    Stereotactic and Functional Neurosurgery 07/2012; 90(5):292-299. · 1.46 Impact Factor
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    ABSTRACT: Objectives: To investigate the effects of rhythmic auditory stimulation (RAS) on gait patterns in comparison with changes after neurodevelopmental treatment (NDT/Bobath) in adults with cerebral palsy. Design: A repeated-measures analysis between the pretreatment and posttreatment tests and a comparison study between groups. Setting: Human gait analysis laboratory. Subjects: Twenty-eight cerebral palsy patients with bilateral spasticity participated in this study. The subjects were randomly allocated to either neurodevelopmental treatment (n = 13) or rhythmic auditory stimulation (n = 15). Interventions: Gait training with rhythmic auditory stimulation or neurodevelopmental treatment was performed three sessions per week for three weeks. Temporal and kinematic data were analysed before and after the intervention. Rhythmic auditory stimulation was provided using a combination of a metronome beat set to the individual's cadence and rhythmic cueing from a live keyboard, while neurodevelopmental treatment was implemented following the traditional method. Main measures: Temporal data, kinematic parameters and gait deviation index as a measure of overall gait pathology were assessed. Results: Temporal gait measures revealed that rhythmic auditory stimulation significantly increased cadence, walking velocity, stride length, and step length (P < 0.05). Kinematic data demonstrated that anterior tilt of the pelvis and hip flexion during a gait cycle was significantly ameliorated after rhythmic auditory stimulation (P < 0.05). Gait deviation index also showed modest improvement in cerebral palsy patients treated with rhythmic auditory stimulation (P < 0.05). However, neurodevelopmental treatment showed that internal and external rotations of hip joints were significantly improved, whereas rhythmic auditory stimulation showed aggravated maximal internal rotation in the transverse plane (P < 0.05). Conclusions: Gait training with rhythmic auditory stimulation or neurodevelopmental treatment elicited differential effects on gait patterns in adults with cerebral palsy.
    Clinical Rehabilitation 02/2012; 26(10):904-14. · 2.19 Impact Factor
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    ABSTRACT: Homogeneous culture of neural precursor cells (NPCs) derived from human pluripotent stem cells (hPSCs) would provide a powerful tool for biomedical applications. However, previous efforts to expand mechanically dissected neural rosettes for cultivation of NPCs remain concerns regarding non-neural cell contamination. In addition, several attempts to purify NPCs using cell surface markers have not demonstrated the expansion capability of the sorted cells. In the present study, we show that polysialic acid-neural cell adhesion molecule (PSA-NCAM) is detected in neural rosette cells derived from hPSCs, and employ PSA-NCAM as a marker for purifying expandable primitive NPCs from the neural rosettes. PSA-NCAM-positive NPCs (termed hNPC(PSA-NCAM+)) were isolated from the heterogeneous cell population of mechanically harvested neural rosettes using magnetic-based cell sorting. The hNPC(PSA-NCAM+) extensively expressed neural markers such as Sox1, Sox2, Nestin, and Musashi-1 (80∼98% of the total cells) and were propagated for multiple passages while retaining their primitive characteristics in our culture condition. Interestingly, PSA-NCAM-negative cells largely exhibited characteristics of neural crest cells. The hNPC(PSA-NCAM+) showed multipotency and responsiveness to instructive cues towards region-specific neuronal subtypes in vitro. When transplanted into the rat striatum, hNPC(PSA-NCAM+) differentiated into neurons, astrocytes, and oligodendrocytes without particular signs of tumorigenesis. Furthermore, Ki67-positive proliferating cells and non-neural lineage cells were rarely detected in the grafts of hNPC(PSA-NCAM+) compared to those of neural rosette cells. Our results suggest that PSA-NCAM-mediated cell isolation provides a highly expandable population of pure primitive NPCs from hPSCs that will lend themselves as a promising strategy for drug screening and cell therapy for neurodegenerative disorders.
    PLoS ONE 01/2012; 7(7):e39715. · 3.73 Impact Factor
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    ABSTRACT: Zinc-finger nucleases (ZFNs) and TAL-effector nucleases (TALENs) are powerful tools for creating genetic modifications in eukaryotic cells and organisms. But wild-type and mutant cells that contain genetic modifications induced by these programmable nucleases are often phenotypically indistinguishable, hampering isolation of mutant cells. Here we show that transiently transfected episomal reporters encoding fluorescent proteins can be used as surrogate genes for the efficient enrichment of endogenous gene-modified cells by flow cytometry.
    Nature Methods 11/2011; 8(11):941-3. · 23.57 Impact Factor
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    ABSTRACT: Dystonia is a symptom defined by involuntary and irregular contractions of the muscles, which cause movement disorders and postural problems. Deep brain stimulation (DBS) in globus pallidus interna (GPi) is a good option for controlling dystonia. DBS has already been shown to have significant effects on primary dystonia as well as Parkinson's disease. Dystonia is very difficult to manage, as seen in cerebral palsy (CP) mixed with spasticity. As CP patients grow, their musculoskeletal problems may require orthopedic surgery. However, the outcome of orthopedic surgery is not usually suitable due to dystonia. Therefore, we attempted to control dystonia through DBS initially and perform orthopedic surgery to correct musculoskeletal deformities after treatment of dystonia. Herein, we report a case that showed remarkable improvement in terms of the dystonia rating scale and gait pattern after combined therapy of DBS and orthopedic surgery.
    Annals of rehabilitation medicine. 10/2011; 35(5):742-6.
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    ABSTRACT: Periventricular leucomalacia has long been investigated as a leading cause of motor and cognitive dysfunction in patients with spastic diplegic cerebral palsy. However, patients with periventricular leucomalacia on conventional magnetic resonance imaging do not always have motor dysfunction and preterm children without neurological abnormalities may have periventricular leucomalacia. In addition, it is uncertain whether descending motor tract or overlying cortical injury is related to motor impairment. To investigate the relationship between motor pathway injury and motor impairment, we conducted voxelwise correlation analysis using tract-based spatial statistics of white matter diffusion anisotropy and voxel-based-morphometry of grey matter injury in patients with periventricular leucomalacia and spastic diplegia (n = 43, mean 12.86 ± 4.79 years, median 12 years). We also evaluated motor cortical and thalamocortical connectivity at resting state in 11 patients using functional magnetic resonance imaging. The functional connectivity results of patients with spastic diplegic cerebral palsy were compared with those of age-matched normal controls. Since γ-aminobutyric acid(A) receptors play an important role in the remodelling process, we measured neuronal γ-aminobutyric acid(A) receptor binding potential with dynamic positron emission tomography scans (n = 27) and compared the binding potential map of the patient group with controls (n = 20). In the current study, white matter volume reduction did not show significant correlation with motor dysfunction. Although fractional anisotropy within most of the major white matter tracts were significantly lower than that of age-matched healthy controls (P < 0.05, family wise error corrected), fractional anisotropy mainly within the bilateral corticospinal tracts and posterior body and isthmus of the corpus callosum showed more significant correlation with motor dysfunction (P < 0.03) than thalamocortical pathways (P < 0.05, family-wise error corrected). Cortical volume of the pre- and post-central gyri and the paracentral lobule tended to be negatively correlated with motor function. The motor cortical connectivity was diminished mainly within the bilateral somatosensory cortex, paracentral lobule, cingulate motor area and visual cortex in the patient group. Thalamovisual connectivity was not diminished despite severe optic radiation injury. γ-Aminobutyric acid(A) receptor binding potential was focally increased within the lower extremity homunculus, cingulate cortex, visual cortex and cerebellum in the patient group (P < 0.05, false discovery rate corrected). In conclusion, descending motor tract injury along with overlying cortical volume reduction and reduced functional connectivity appears to be a leading pathophysiological mechanism of motor dysfunction in patients with periventricular leucomalacia. Increased regional γ-aminobutyric acid(A) receptor binding potential appears to result from a compensatory plasticity response after prenatal brain injury.
    Brain 03/2011; 134(Pt 4):1199-210. · 9.92 Impact Factor
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    ABSTRACT: Constraint-induced movement therapy (CIMT) has emerged as a promising therapeutic strategy for improving affected upper limb function in children with hemiplegic cerebral palsy (CP). However, little is known about the changes in the brain that are induced by CIMT. This study was designed to investigate these changes and behavioural performance after CIMT intervention in mice with neonatal hypoxic-ischemic brain injury. We utilized the neonatal hypoxic-ischemic brain injury model established in mice pups. Three weeks after the injury, the mice were randomly assigned to the following three groups: the control group (n = 15), the enriched-environment group (n = 17), and the CIMT with an enriched-environment group (CIMT-EE, n = 15). 5-bromo-2-deoxyuridine (BrdU) was injected daily to label proliferating cells during the 2 weeks of intervention. The CIMT-EE group showed better fall rate in the horizontal ladder rung walking test (mean 5.4%, SD 3.6%) than either the control (mean 14.3%, SD 7.3%; p = 0.001) or enriched-environment (mean 12.4%, SD 7.7%; p = 0.010) groups 2 weeks after the end of intervention. The CIMT-EE group also showed more neurogenesis (mean 7069 cells/mm³, SD 4017 cells/mm³) than either the control group (mean 1555 cells/mm³, SD 1422 cells/mm³; p < 0.001) or enriched-environment group (mean 2994 cells/mm³, SD 3498 cells/mm³; p = 0.001) in the subventricular zone. In the striatum, neurogenesis in the CIMT-EE group (mean 534 cells/mm³, SD 441 cells/mm³) was greater than in the control group (mean 95 cells/mm³, SD 133 cells/mm³; p = 0.001). There was CIMT-EE enhanced neurogenesis in the brain along with functional benefits in mice after early hypoxic-ischemic brain injury. This is the first study to demonstrate the effects of CIMT on neurogenesis and functional recovery after experimental injury to an immature brain.
    Developmental Medicine & Child Neurology 01/2011; 53(4):327-33. · 2.68 Impact Factor

Publication Stats

140 Citations
78.75 Total Impact Points

Institutions

  • 2008–2014
    • Yonsei University Hospital
      • Department of Internal Medicine
      Sŏul, Seoul, South Korea
  • 2012–2013
    • Yonsei University
      Sŏul, Seoul, South Korea
    • Ewha Womans University
      Sŏul, Seoul, South Korea
  • 2011
    • Myongji University
      Sŏul, Seoul, South Korea