• Annals of Clinical Neurophysiology
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• 제17권1호
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• pp.1-16
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• 2015

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that is characterized by progressive death of motor neurons in the cortex, brainstem, and spinal cord. Until now, many treatment strategies have been tested in ALS, but so far only Riluzole has shown efficacy of slightly slowing disease progression. The pathophysiological mechanisms underlying ALS are multifactorial, with a complex interaction between genetic factors and molecular pathways. Other motor neuron disease such as spinal muscular atrophy (SMA) and spinobulbar muscular atrophy (SBMA) are also progressive neurodegenerative disease with loss of motor neuron as ALS. This common thread of motor neuron loss has provided a target for the development of therapies for these motor neuron diseases. A better understanding of these pathogenic mechanisms and the potential pathological relationship between the various cellular processes have suggested novel therapeutic approaches, including stem cell and genetics-based strategies, providing hope for feasible treatment of ALS.

• 한국전문물리치료학회지
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• 제2권1호
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• pp.62-70
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• 1995

The use of electricity to evoke s skeletal muscle response is FES, which is a form of functional electrical stimulation. In the case of the damaged spinal cord, the technique can supply stimulation to the lower moter neurons and their muscle fiber, which have been disconnected from control of the higher nervous system. Recent advances in electronics, particularly miniaturization, have made possible the design of much improved systems of electrodes and stimulaters for FES. Clinical research has followed two main lines: the use of FES in the upper extremities for producing functional hand rehabilitation in quadriplegics and in the lower extremities for producing standing and gait in paraplegics.

• Molecules and Cells
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• 제20권3호
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• pp.315-324
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• 2005

Pain is an unpleasant sensation experienced when tissues are damaged. Thus, pain sensation in some way protects body from imminent threat or injury. Peripheral sensory nerves innervated to peripheral tissues initially respond to multiple forms of noxious or strong stimuli, such as heat, mechanical and chemical stimuli. In response to these stimuli, electrical signals for conducting the nociceptive neural signals through axons are generated. These action potentials are then conveyed to specific areas in the spinal cord and in the brain. Sensory afferent fibers are heterogeneous in many aspects. For example, sensory nerves are classified as $A{\alpha}$, $-{\beta}$, $-{\delta}$ and C-fibers according to their diameter and degree of myelination. It is widely accepted that small sensory fibers tend to respond to vigorous or noxious stimuli and related to nociception. Thus these fibers are specifically called nociceptors. Most of nociceptors respond to noxious mechanical stimuli and heat. In addition, these sensory fibers also respond to chemical stimuli [Davis et al. (1993)] such as capsaicin. Thus, nociceptors are considered polymodal. Recent advance in research on ion channels in sensory neurons reveals molecular mechanisms underlying how various types of stimuli can be transduced to neural signals transmitted to the brain for pain perception. In particular, electrophysiological studies on ion channels characterize biophysical properties of ion channels in sensory neurons. Furthermore, molecular biology leads to identification of genetic structures as well as molecular properties of ion channels in sensory neurons. These ion channels are expressed in axon terminals as well as in cell soma. When these channels are activated, inward currents or outward currents are generated, which will lead to depolarization or hyperpolarization of the membrane causing increased or decreased excitability of sensory neurons. In order to depolarize the membrane of nerve terminals, either inward currents should be generated or outward currents should be inhibited. So far, many cationic channels that are responsible for the excitation of sensory neurons are introduced recently. Activation of these channels in sensory neurons is evidently critical to the generation of nociceptive signals. The main channels responsible for inward membrane currents in nociceptors are voltage-activated sodium and calcium channels, while outward current is carried mainly by potassium ions. In addition, activation of non-selective cation channels is also responsible for the excitation of sensory neurons. Thus, excitability of neurons can be controlled by regulating expression or by modulating activity of these channels.

• Journal of Dental Anesthesia and Pain Medicine
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• 제16권2호
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• pp.137-140
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• 2016

Spinal muscular atrophy (SMA) is an autosomal recessive, severe neuromuscular disorder in which degeneration of alpha motor neurons in the spine progressively weakens and ultimately paralyzes the proximal muscles. It occurs in one per 6,000-10,000 infants, and is a genetic disorder with the second-highest mortality rate worldwide. An 18-year-old male patient with SMA was referred for general anesthesia for difficulty in performing dental treatment due to limited mouth opening caused by temporomandibular joint (TMJ) pain. However, the patient had a high risk of general anesthesia complications, so TMJ pain during mouth opening was reduced through local anesthesia of the TMJ. Fortunately, the anesthesia was successful in reducing pain during mouth opening, enabling the patient to receive dental treatment with an adequate mouth opening.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2002년도 Current Trends in Toxicological Sciences
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• pp.14-23
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• 2002

The nervous system consists of two types of cells, which are neurons and glial cells. Among the glial cells, oligodendrodendrocytes and schwann cells form myelin sheaths in the central nervous system (CNS) and the peripheral nervous system (PNS), respectively. The major function of myelin in vertebrates is to insulate axonal and help action potential travel faster.(omitted)

• The Korean Journal of Pain
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• 제22권3호
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• pp.210-215
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• 2009

Background: Several studies have indicated that a nerve injury enhances the expression of the voltage-gated calcium channel ${\alpha}2{\delta}1$ subunit (Cav ${\alpha}2{\delta}1$) in sensory neurons and the dorsal spinal cord. This study examined whether NMDA receptor activation is essential for Cav ${\alpha}2{\delta}1$-mediated tactile allodynia in Cav ${\alpha}2{\delta}1$ overexpressing transgenic mice and L5/6 spinal nerve ligated rats (SNL). These two models show similar Cav ${\alpha}2{\delta}1$ upregulation and behavioral hypersensitivity, without and with the presence of other injury factors, respectively. Methods: The transgenic (TG) mice were generated as described elsewhere (Feng et al., 2000). The left L5/6 spinal nerves in the Harlan Sprague Dawley rats were ligated tightly (SNL) to induce neuropathic pain, as described by Kim et al. (1992). Memantine 2 mg/kg (10 ul) was injected directly into the L5/6 spinal region followed by $10{\mu}l$ saline. Tactile allodynia was tested for any mechanical hypersensitivity. Results: The tactile allodynia in the SNL rats could be reversed by an intrathecal injection of memantine 2 mg/kg at 1.5 hours. The tactile allodynia in the Cav ${\alpha}2{\delta}1$ over-expressing TG mice could be reversed by an intrathecal injection of memantine 2 mg/kg at 1.5, 2.0 and 2.5 hours. Conclusions: The behavioral hypersensitivity was similar in the TG mice and nerve injury pain model, supporting the hypothesis that elevated Cav ${\alpha}2{\delta}1$ mediates similar pathways that underlie the pain states in both models. The selective activation of spinal NMDA receptors plays a key role in mediating the pain states in both the nerve-injury rats and TG mice.

• The Korean Journal of Pain
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• 제25권4호
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• pp.213-220
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• 2012

Background: It has been demonstrated that the expression of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and apoptotic cell death in the dorsal root ganglion (DRG) following spinal nerve constriction injury play a role in the initiation and continuation of hyperalgesia and allodynia. The present study was designed to investigate the effects of ethyl pyruvate (EP) on mechanical and cold allodynia, TNF-${\alpha}$ expression, and apoptosis in DRG after spinal nerve ligation injury. Methods: Rats were divided into 3 groups: control, pre-EP, and post-EP. EP (50 mg/kg) was intraperitoneally injected 30 minutes before (pre-EP) or after (post-EP) surgery. Behavioral tests to determine mechanical and cold allodynia were conducted before surgery and 4 and 7 days after surgery. Seven days after surgery, TNF-${\alpha}$ protein levels in DRG were evaluated by enzyme-linked immunosorbent assay, and DRG apoptosis was determined by immunohistochemical detection of activated caspase-3. Results: Treatment with EP significantly reduced mechanical and cold allodynia following spinal nerve ligation injury. TNF-${\alpha}$ protein levels in the pre-EP ($4.7{\pm}1.2$ pg/200 ${\mu}g$; P < 0.001) and post-EP ($6.4{\pm}1.8$ pg/200 ${\mu}g$; P < 0.001) groups were 2-3 times lower than the control group ($14.4{\pm}1.2$ pg/200 ${\mu}g$). The percentages of neurons and satellite cells that co-localized with caspase-3 were also significantly lower in the pre-EP and post-EP groups than the control group. Conclusions: These results demonstrate that EP has a strong anti-allodynic effect that acts through the inhibition of TNF-${\alpha}$ expression and apoptosis in DRG after spinal nerve ligation injury.

• Journal of Korean Neurosurgical Society
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• 제57권6호
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• pp.445-454
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• 2015

Objective : In the present study we analyzed neuroprotective and antiapoptotic effect of the difumarate salt S-15176, as an anti-ischemic, an antioxidant and a stabilizer of mitochondrial membrane in secondary damage following spinal cord injury (SCI) in a rat model. Methods : Three groups were performed with 30 Wistar rats; control (1), trauma (2), and a trauma+S-15176 (10 mg/kg i.p., dimethyl sulfoxide) treatment (3). SCI was performed at the thoracic level using the weight-drop technique. Spinal cord tissues were collected following intracardiac perfusion in 3rd and 7th days of posttrauma. Hematoxylin and eosin staining for histopatology, terminal deoxynucleotidyl transferase dUTP nick end labeling assay for apoptotic cells and immunohistochemistry for proapoptotic cytochrome-c, Bax and caspase 9 were performed to all groups. Functional recovery test were applied to each group in 3rd and 7th days following SCI. Results : In trauma group, edematous regions, diffuse hemorrhage, necrosis, leukocyte infiltration and severe degeneration in motor neurons were observed prominently in gray matter. The number of apoptotic cells was significantly higher (p<0.05) than control group. In the S-15176-treated groups, apoptotic cell number in 3rd and 7th days (p<0.001), also cytochrome-c (p<0.001), Bax (p<0.001) and caspase 9 immunoreactive cells (p<0.001) were significantly decreased in number compared to trauma groups. Hemorrhage and edema in the focal areas were also noticed in gray matter of treatment groups. Results of the locomotor test were significantly increased in treatment group (p<0.05) when compared to trauma groups. Conclusion : We suggest that difumarate salt S-15176 prevents mitochondrial pathways of apoptosis and protects spinal cord from secondary injury and helps to preserve motor function following SCI in rats.

• International Journal of Stem Cells
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• 제17권3호
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• pp.236-252
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• 2024

Spinal cord injury (SCI) is a serious nervous system disease that usually leads to the impairment of the motor, sensory, and autonomic nervous functions of the spinal cord, and it places a heavy burden on families and healthcare systems every year. Due to the complex pathophysiological mechanism of SCI and the poor ability of neurons to regenerate, the current treatment scheme has very limited effects on the recovery of spinal cord function. In addition, due to their unique advantages, exosomes can be used as carriers for cargo transport. In recent years, some studies have confirmed that treatment with mesenchymal stem cells (MSCs) can promote the recovery of SCI nerve function. The therapeutic effect of MSCs is mainly related to exosomes secreted by MSCs, and exosomes may have great potential in SCI therapy. In this review, we summarized the repair mechanism of mesenchymal stem cells-derived exosomes (MSCs-Exos) in SCI treatment and discussed the microRNAs related to SCI treatment based on MSCs-Exos and their mechanism of action, which is helpful to further understand the role of exosomes in SCI.

• The Journal of Korean Physical Therapy
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• 제13권2호
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• pp.335-346
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• 2001

This study was performed, using c-fos, to investigate the effect of TENS on pain model induced by capsaicin in spinal level. Twelve rats with 200-250g body weight were randomly divided into three groups: One group which induced by capsaicin, another group which applicated TENS with low frequency(4Hz. 200${\mu}$s, 20min) and the other group which applicated TENS with high frequency(100Hz, 50${\mu}$s, 20 min). The results of this study were as follows: 1. The number of c-fos immunoreactive neurons in superficial dorsal horn was increased markedly 2 hours after capsaicin injection, and decreased gradually from 4 hours to 16 hours after injection. 2. At 2hours after capsaicin injection, both low frequency and high frequency TENS decrease the number of c-fos immunoreactive neurons in superficial dorsal horn .3. In acute pain model, low frequency TENS greatly decrease c-fos expression than high frequency TENS. Therefore. decreasing the number of c-fos immunoreactive neurons which increased after capsaicin injection with application of TENS indicate that both of the TENS have inhibitory effect. In addition. low frequency TENS greatly decreased the number of neurons explains low frequency TENS is more effective than high frequency TENS in acute pain. This study also can become a part of scientific evidence on electrotherapy through measuring quantitively effects of TENS in pain model.