• Journal of Korean Neurosurgical Society
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• 제61권1호
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• pp.10-18
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• 2018

Objective : To investigates the effect of curcumin on proliferation of spinal cord neural stem/progenitor cells (SC-NSPCs) and functional outcome in a rat spinal cord injury (SCI) model. Methods : Sixty adult male Sprague-Dawley rats were randomly and blindly allocated into three groups (sham control group; curcumin treated group after SCI; vehicle treated group after SCI). Functional recovery was evaluated by the Basso, Beattie, and Bresnahan (BBB) scale during 6 weeks after SCI. The expression of SC-NSPC proliferation and astrogliosis were analyzed by nestin/Bromodeoxyuridine (BrdU) and Glial fibrillary acidic protein (GFAP) staining. The injured spinal cord was then examined histologically, including quantification of cavitation. Results : The BBB score of the SCI-curcumin group was better than that of SCI-vehicle group up to 14 days (p<0.05). The coimmunoreactivity of nestin/BrdU in the SCI-curcumin group was much higher than that of the SCI-vehicle group 1 week after surgery (p<0.05). The GFAP immunoreactivity of the SCI-curcumin group was remarkably lower than that of the SCI-vehicle group 4 weeks after surgery (p<0.05). The lesion cavity was significantly reduced in the curcumin group as compared to the control group (p<0.05). Conclusion : These results indicate that curcumin could increase the expression of SC-NSPCs, and reduce the activity of reactive astrogliosis and lesion cavity. Consequently curcumin could improve the functional recovery after SCI via SC-NSPC properties.

• 생명과학회지
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• 제26권12호
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• pp.1355-1359
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• 2016

인간 중간엽 줄기세포(hMSCs)는 신경세포(neuron-like cells)를 포함한 다양한 세포로 분화할 수 있는 능력을 지닌 성체 줄기세포(adult stem cells)이다. 본 연구에서는 인간의 골수유래-중간엽 줄기세포(bone marrow-mesenchymal stem cells; hBM-MSCs)를 이용한 신경분화에서 신경세포 표지자(neuronal marker)인 NF-M, Tuj-1 뿐만 아니라 성상세포 표지자(glial marker)인 GFAP의 발현 역시 의미 있게 증가함을 real-time PCR, Western blot, and immunocytochemical staining법을 통하여 관찰하였다. 이를 개선하기 위하여, 신경분화에 중요한 신호전달자(signal intermediator)인 PDE4를 억제한 후 신경분화를 유도하였다. PDE4 억제자인 rolipram 혹은 resveratrol를 각각 처리하여 신경분화한 줄기세포(Roli- or RSV-dMSCs)에서 NF-M, Tuj-1의 발현이 증가하였고 반면, GFAP의 발현은 감소함을 real-time PCR, Western blot, and immunocytochemical staining법을 통하여 관찰하였다. 본 연구를 통하여, PDE4를 조절하며 줄기세포의 신경분화를 개선할 수 있음을 보였다.

• 동의신경정신과학회지
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• 제17권1호
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• pp.37-57
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• 2006

Objective : This research investigates the effect of the CMT and MCMT on Alzheimer‘s disease. Methods : The effects of the CMT and MCMT extract on (1) amyloid precursor proteins(APP), acetylcholinesterase(AChE) mRNA of PC-12 cells treated with CT-105; (2) the AChE activity and the APP production of PC-12 cell treated with CT-105; (3) the behavior; (4) expression of $IL-1{\beta}$, $TNF-{\alpha}$, MDA, GFAP, CD68 abd CD11b; (5) the infarction area of the hippocampus in Alzheimer's diseased mice induced with ${\beta}A$ were investigated. Results : 1. The CMT and MCMT extract suppressed the expression of APP, AChE, and mRNA in PC-12 cells treated with CT-105. 2. The CMT and MCMT extract suppressed the AChE activity, and the production of APP significantly in PC-12 cells treated with CT-105. 3. For the CMT and MCMT extract group a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer's disease induced by ${\beta}A$ in the Morris water maze experiment, which measured stop-through latency, and distance movement-through latency. 4. The CMT and MCMT extract suppressed the over-expression of $IL-1{\beta}$, $TNF-{\alpha}$, MDA, GFAP, CD68 abd CD11bCD68/GFAP, in the mice with Alzheimer's disease induced by ${\beta}A$. 5. The CMT and MCMT extract reduced the infarction area of hippocampus with Alzheimer's disease induced by ${\beta}A$ 6. The MCMT showed more excellent effects than CMT in the every experiments except PC-12 cells. Conclusions : These results suggest that the CMT and MCMT extract may be effective for the prevention and treatment of Alzheimer's disease. Investigation into the clinical use of the CMT and MCMT extract for Alzheimer's disease is suggested for future research.

• The Korean Journal of Pain
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• 제33권1호
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• pp.23-29
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• 2020

Background: Neuropathic pain (NP) is considered a clinically incurable condition despite various treatment options due to its diverse causes and complicated disease mechanisms. Since the early 2000s, multipotent human mesenchymal stem cells (hMSCs) have been used in the treatment of NP in animal models. However, the effects of hMSC injections have not been studied in chronic post-ischemia pain (CPIP) mice models. Here, we investigated whether intrathecal (IT) and intrapaw (IP) injections of hMSCs can reduce mechanical allodynia in CPIP model mice. Methods: Seventeen CPIP C57/BL6 mice were selected and randomized into four groups: IT sham (n = 4), IT stem (n = 5), IP sham (n = 4), and IP stem (n = 4). Mice in the IT sham and IT stem groups received an injection of 5 μL saline and 2 × 10⁴ hMSCs, respectively, while mice in the IP sham and IP stem groups received an injection of 5 μL saline and 2 × 10⁵ hMSCs, respectively. Mechanical allodynia was assessed using von Frey filaments from pre-injection to 30 days post-injection. Glial fibrillary acidic protein (GFAP) expression in the spinal cord and dorsal root ganglia were also evaluated. Results: IT and IP injections of hMSCs improved mechanical allodynia. GFAP expression was decreased on day 25 post-injection compared with the sham group. Injections of hMSCs improved allodynia and GFAP expression was decreased compared with the sham group. Conclusions: These results suggested that hMSCs may be also another treatment modality in NP model by ischemia-reperfusion.

• Biomolecules & Therapeutics
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• 제25권3호
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• pp.259-265
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• 2017

This study aimed to investigate the analgesic effect of substance P (SP) in an animal model of neuropathic pain. An experimental model of neuropathic pain, the chronic constriction injury (CCI) model, was established using ICR mice. An intravenous (i.v.) injection of SP (1 nmole/kg) was administered to the mice to examine the analgesic effects of systemic SP on neuropathic pain. Behavioral testing and immunostaining was performed following treatment of the CCI model with SP. SP attenuated mechanical allodynia in a time-dependent manner, beginning at 1 h following administration, peaking at 1 day post-injection, and decaying by 3 days post-injection. The second injection of SP also increased the threshold of mechanical allodynia, with the effects peaking on day 1 and decaying by day 3. A reduction in phospho-ERK and glial fibrillary acidic protein (GFAP) accompanied the attenuation of mechanical allodynia. We have shown for the first time that i.v. administration of substance P attenuated mechanical allodynia in the maintenance phase of neuropathic pain using von Frey's test, and simultaneously reduced levels of phospho-ERK and GFAP, which are representative biochemical markers of neuropathic pain. Importantly, glial cells in the dorsal horn of the spinal cord (L4-L5) of SP-treated CCI mice, expressed the anti-inflammatory cytokine, IL-10, which was not seen in vehicle saline-treated mice. Thus, i.v. administration of substance P may be beneficial for improving the treatment of patients with neuropathic pain, since it decreases the activity of nociceptive factors and increases the expression of anti-nociceptive factors.

• Molecules and Cells
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• 제26권2호
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• pp.186-192
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• 2008

NELL2, a neural tissue-enriched protein, is produced in the embryo, and postembryonically in the mammalian brain, with a broad distribution. Although its synthesis is required for neuronal differentiation in chicks, not much is known about its function in the adult mammalian brain. We investigated the distribution of NELL2 in various regions of the adult rat brain to study its potential functions in brain physiology. Consistent with previous reports, NELL2-immunoreactivity (ir) was found in the cytoplasm of neurons, but not in glial fibrillary acidic protein (GFAP)-positive glial cells. The highest levels of NELL2 were detected in the hippocampus and the cerebellum. Interestingly, in the cerebellar cortex NELL2 was observed only in the GABAergic Purkinje cells not in the excitatory granular cells. In contrast, it was found mainly in the hippocampal dentate gyrus and pyramidal cell layer that contains mainly glutamatergic neurons. In the dentate gyrus, NELL2 was not detected in the GFAP-positive neural precursor cells, but was generally present in mature neurons of the subgranular zone, suggesting a role in this region restricted to mature neurons.

• Journal of Genetic Medicine
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• 제10권2호
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• pp.88-93
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• 2013

Alexander disease (ALXD) is a rare demyelinating disease of the white matter of the brain that is caused by a mutation in the glial fibrillary acidic protein (GFAP) gene. The overexpression of GFAP in astrocytes induces a failure in the developmental growth of the myelin sheath. The neurodegenerative destruction of the myelin sheath of the white matter is accompanied by an accumulation of abnormal deposits of Rosenthal fibers in astrocytes, which is the hallmark of ALXD. The disease can be divided into four groups based on the onset age of the patients: neonatal, infantile, juvenile, or adult. Early-onset disease is more severe, progresses rapidly, and results in a shorter life span than late-onset cases. Magnetic resonance imaging and genetic tests are mostly used for diagnostic purposes. Pathological tests of brain tissue for Rosenthal fibers are definitive diagnostic methods. Therapeutic strategies are being investigated. Ceftriaxone, which is an enhancer of glial glutamate transporter (GLT-1) expression, is currently in clinical trials for the treatment of patients with ALXD. To date, there are no clinically available treatments. The cause, pathology, pathophysiology, inheritance, clinical features, diagnosis, and treatment of ALXD will be reviewed comprehensively.

• 대한약침학회지
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• 제20권4호
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• pp.257-264
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• 2017

Introduction: Pharmacopuncture, which combines acupuncture with herbal medicine, is one of the newly developed acupuncture techniques that has recently been put into use. The possible mechanisms of scolopendra pharmacopuncture, as well as its potential effects on depressive symptoms, were investigated in this study by using a mouse model of chronic immobilization stress (CIS). Methods: C57BL/6 male mice were randomly assigned into three groups: mice not stressed with restraint and injected with distilled water, mice stressed with restraint and injected with distilled water, and mice stressed with restraint injected with scolopendra pharmacopuncture at a cervical site. Behavioral tests (an open field test, tail suspension test, and forced swimming test) were carried out after two weeks of CIS and injection treatments. The expression levels of glial fibrillary acidic protein (GFAP) in the hippocampus were determined by using western blot and immunohistochemistry analyses. Results: Mice exposed to CIS showed decreased behavioral activity, while scolopendra pharmacopuncture treatment significantly protected against the depressive-like behaviors induced by CIS. Moreover, scolopendra pharmacopuncture treatment increased GFAP protein levels in the hippocampi of the mice stressed by chronic immobilization. Conclusion: Scolopendra pharmacopuncture has an ameliorating effect on depressive behavior, which is partially mediated through protection against glial loss in the hippocampus.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제40권4호
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• pp.173-180
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• 2014

Objectives: The purpose of this study was to investigate the neurogenic differentiation of human dental pulp stem cells (DPSCs), periodontal ligament stem cells (PDLSCs), and stem cells from apical papilla (SCAP). Materials and Methods: After induction of neurogenic differentiation using commercial differentiation medium, expression levels of neural markers, microtubule-associated protein 2 (MAP2), class III ${\beta}$-tubulin, and glial fibrillary acidic protein (GFAP) were identified using reverse transcriptase polymerase chain reaction (PCR), real-time PCR, and immunocytochemistry. Results: The induced cells showed neuron-like morphologies, similar to axons, dendrites, and perikaryons, which are composed of neurons in DPSCs, PDLSCs, and SCAP. The mRNA levels of neuronal markers tended to increase in differentiated cells. The expression of MAP2 and ${\beta}$-tubulin III also increased at the protein level in differentiation groups, even though GFAP was not detected via immunocytochemistry. Conclusion: Human dental stem cells including DPSCs, PDLSCs, and SCAP may have neurogenic differentiation capability in vitro. The presented data support the use of human dental stem cells as a possible alternative source of stem cells for therapeutic utility in the treatment of neurological diseases.

• 생명과학회지
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• 제23권1호
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• pp.125-130
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• 2013

Calponin 3는 F-actin과 결합하는 단백질로 신경계의 가소성과 시냅스 활성을 조절하는데 중요한 역할을 하는 것으로 알려져 있다. 평활근과 심장근에 발현되는 calponin 1과 calponin 2와는 다르게 calponin 3는 뇌 조직에 많이 발현되어 있는 것으로 보고되고 있다. 본 연구는 마우스에서 3-nitropropionic acid를 투여하여 선조체에 비가역적 신경 손상을 주었을 때 calponin 3의 발현 양상을 알아보기 위하여 진행되었다. 본 연구 결과 3-nitropropionic acid를 마우스에 투여하였을 때 선조체에서 신경조직의 괴사가 일어남을 관찰하였으며 calponin 3는 약물 투여 후 1.5일부터 서서히 발현되는 것을 확인하였다. 특히, calponin 3는 신경조직의 괴사가 일어나는 부위의 주변부에서 발현되는 것을 확인하였으며 형광 이중면역 염색법으로 확인한 결과 GFAP를 발현하는 별아교세포에서 발현됨을 최초로 밝혔다. 따라서, calponin 3가 3-nitropropionic acid의 독성에 저항성을 나타내는 부위에서 별아교세포에서만 특이적으로 발현되는 것으로 보아 calponin 3는 별아교세포에 의한 신경아교증에 중요한 역할을 하는 것으로 추측된다.