• The Korean Journal of Physiology and Pharmacology
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• 제12권6호
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• pp.299-306
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• 2008

Sometimes, spinal cord injury (SCI) results in various chronic neuropathic pain syndromes that occur diffusely below the level of the injury. It has been reported that behavioral signs of neuropathic pain are expressed in the animal models of contusive SCI. However, the observation period is relatively short considering the natural course of pain in human SCI patients. Therefore, this study was undertaken to examine the time course of mechanical and cold allodynia in the hindpaw after a spinal cord contusion in rats for a long period of time (30 weeks). The hindpaw withdrawal threshold to mechanical stimulation was applied to the plantar surface of the hindpaw, and the withdrawal frequency to the application of acetone was measured before and after a spinal contusion. The spinal cord contusion was produced by dropping a 10 g weight from a 6.25 and 12.5 mm height using a NYU impactor. After the injury, rats showed a decreased withdrawal threshold to von Frey stimulation, indicating the development of mechanical allodynia which persisted for 30 weeks. The withdrawal threshold between the two experimental groups was similar. The response frequencies to acetone increased after the SCI, but they were developed slowly. Cold allodynia persisted for 30 weeks in 12.5 mm group. The sham animals did not show any significant behavioral changes. These results provide behavioral evidence to indicate that the below-level pain was well developed and maintained in the contusion model for a long time, suggesting a model suitable for pain research, especially in the late stage of SCI or for long term effects of analgesic intervention.

• The Korean Journal of Physiology
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• 제22권1호
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• pp.89-100
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• 1988

Effect of clonidine on the dorsal horn cell responses to mechanical stimulations were studies in 3 spinalized cats and 10 cats with intact spinal cord. The type of dorsal horn cells was determined according to their response patterns to four graded mechanical stimulations (brush, pressure, pinch and squeeze) applied to the respective receptive fields. In the present study the results obtained only from the wide dynamic range (WDR) cells were included. The responses of the WDR cells to noxious mechanical stimuli were selectively suppressed following intravenous administration of clonidine into the experimental animals. The clonidine-induced changes in responses of the WDR cells to mechanical stimulation were not affected by naloxone or propranolol whereas effect of clonidine on WDR cell responses was almost completely abolished after intravenous administration of yohimbine. Also in the spinalized cats results parallel to those observed in cats with intact spinal cord were obtained. The results of present study strongly implies that analgesic action of clonidine can be mediated through excitation of ${\alpha}_{2}-adrenoceptor$ even at the spinal cord level without supraspinal mechanism.

• Journal of Korean Neurosurgical Society
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• 제59권5호
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• pp.437-441
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• 2016

Objective : Recently, regenerative therapies have been used in clinical trials (heart, cartilage, skeletal). We don't make use of these treatments to spinal cord injury (SCI) patients yet, but regenerative therapies are rising interest in recent study about SCI. Neural precursor/stem cell (NPSC) proliferation is a significant event in functional recovery of the central nervous system (CNS). However, brain NPSCs and spinal cord NPSCs (SC-NPSCs) have many differences including gene expression and proliferation. The purpose of this study was to investigate the influence of neural growth factor (NGF) on the proliferation of SC-NPSCs. Methods : NPSCs ($2{\times}10^4$) were suspended in $100{\mu}L$ of neurobasal medium containing NGF-7S (Sigma-Aldrich) and cultured in a 96-well plate for 12 days. NPSC proliferation was analyzed five times for either concentration of NGF (0.02 and 2 ng/mL). Sixteen rats after SCI were randomly allocated into two groups. In group 1 (SCI-vehicle group, n=8), animals received 1.0 mL of the saline vehicle solution. In group 2 (SCI-NGF group, n=8), the animals received single doses of NGF (Sigma-Aldrich). A dose of 0.02 ng/mL of NGF or normal saline as a vehicle control was intra-thecally injected daily at 24 hour intervals for 7 days. For Immunohistochemistry analysis, rats were sacrificed after one week and the spinal cords were obtained. Results : The elevation of cell proliferation with 0.02 ng/mL NGF was significant (p<0.05) but was not significant for 2 ng/mL NGF. The optical density was increased in the NGF 0.02 ng/mL group compared to the control group and NGF 2 ng/mL groups. The density of nestin in the SCI-NGF group was significantly increased over the SCI-vehicle group (p<0.05). High power microscopy revealed that the density of nestin in the SCI-NGF group was significantly increased over the SCI-vehicle group. Conclusion : SC-NPSC proliferation is an important pathway in the functional recovery of SCI. NGF enhances SC-NPSC proliferation in vitro and in vivo. NGF may be a useful option for treatment of SCI patients pending further studies to verify the clinical applicability.

• Journal of Korean Neurosurgical Society
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• 제46권4호
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• pp.397-402
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• 2009

Objective : In this study, the authors assessed the ability of rat bone marrow derived mesenchymal stem cells (BMDMSCs), in the presence of a growth factor, fibroblast growth factor-4 (FGF-4) and hydroxyapatite, to act as a scaffold for posterolateral spinal fusion in a rat model. Methods : Using a rat posterolateral spine fusion model. the experimental study comprised 3 groups. Group 1 was composed of 6 animals that were implanted with 0.08 gram hydroxyapatite only. Group 2 was composed of 6 animals that were implanted with 0.08 gram hydroxyapatite containing $1{\times}10^6/60{\mu}L$ rat of BMDMSCs. Group 3 was composed of 6 animals that were implanted with 0.08 gram hydroxyapatite containing $1{\times}10^6/60{\mu}L$ of rat BMDMSCs and FGF-4 $1{\mu}G$ to induce the bony differentiation of the BMDMSCs. Rats were assessed using radiographs obtained at 4, 6, and 8 weeks postoperatively. After sacrifice, spines were explanted and assessed by manual palpation, high-resolution microcomputerized tomography, and histological analysis. Results : Radiographic, high-resolution microcomputerized tomographic, and manual palpation revealed spinal fusion in five rats (83%) in Group 2 at 8 weeks. However, in Group 1, three (60%) rats developed fusion at L4-L5 by radiography and two (40%) by manual palpation in radiographic examination. In addition, in Group 3, bone fusion was observed in only 50% of rats by manual palpation and radiographic examination at this time. Conclusion : The present study demonstrates that 0.08 gram of hydroxyapatite with $1{\times}10^6/60{\mu}L$ rat of BMDMSCs induced bone fusion. FGF4, added to differentiate primitive $1{\times}10^6/60{\mu}L$ rat of BMDMSCs did not induce fusion. Based on histologic data, FGF-4 appears to induce fibrotic change rather than differentiation to bone by $1{\times}10^6/60{\mu}L$ rat of BMDMSCs.

• ETRI Journal
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• 제35권6호
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• pp.1029-1037
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• 2013

This paper introduces a novel and fast synthesizing method for 3D motions of quadrupedal animals that uses only a small set of motion capture data. Unlike human motions, animal motions are relatively difficult to capture. Also, it is a challenge to synthesize continuously changing animal motions in real time because animals have various gait types according to their speed. The algorithm proposed herein, however, is able to synthesize continuously varying motions with proper limb configuration by using only one single cyclic animal motion per gait type based on the biologically driven Froude number. During the synthesis process, each gait type is automatically determined by its speed parameter, and the transition motions, which have not been entered as input, are synthesized accordingly by the optimized asynchronous motion blending technique. At the start time, given the user's control input, the motion path and spinal joints for turning are adjusted first and then the motion is stitched at any speed with proper transition motions to synthesize a long stream of motions.

• 동의생리병리학회지
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• 제25권2호
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• pp.217-226
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• 2011

The aim of this study is to identify central neural pathway of neurons following the projection to the large intestine and Hapgok(LI4) which is Won acupoint of the large intestine meridian of hand-yangmyeong. In this experiment, Bartha's strain of pseudorabies virus was used to trace central localization of neurons related with large intestine and acupoint(LI4) which has been known to be able to regulate intestinal function. The animals were divided into 3 groups: group 1, injected into the large intestine; group 2, injected into the acupoint(LI4); group 3, injected into the acupoint(LI4) after severing the radial, ulnar, median nerve. After four days survival of rats, PRV labeled neurons were identified in the spinal cord and brain by immunohistochemical method. First-order PRV labeled neurons following the projection to large intestine, acupoint(LI4) and acupoint(LI4) after cutting nerve were found in the cervical, thoracic, lumbar and sacral spinal cord. Commonly labeled neurons were labeled in the lumbosacral spinal cord and thoracic spinal cord. They were found in lamina V- X, intermediomedial nucleus and dorsal column area. The area of sensory neurons projecting was L5-S2 spinal ganglia and T12-L1 spinal ganglia, respectively. In the brainstem, the neurons were labeled most evidently and consistently in the nucleus tractus solitarius, area postrema, dorsal motor nucleus of vagus nerve, reticular nucleus, raphe nuclei(obscurus, magnus and pallidus), C3 adrenalin cells, parapyramidal area(lateral paragigantocellular nucleus), locus coeruleus, subcoeruleus nucleus, A5 cell group, periaqueductal gray matter. In the diencephalon, PRV labeled neurons were marked mostly in the arcuate nucleus and median eminence. These results suggest that overlapped CNS locations are related with autonomic nuclei which regulate the functions of large intestine-related organs and it was revealed by tracing PRV labeled neurons projecting large intestine and related acupoint(LI4).

• Journal of Chest Surgery
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• 제34권11호
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• pp.823-830
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• 2001

배경: 흉부나 흉복부 대동맥 수술중 대동맥 혈류의 일시적 차단에 의해 유발되는 낮은 혈류압으로 인한 척추신경의 허혈성 손상에 의한 하지마비는 심각한 수술 합병증으로 남아 있다. 심장이나 뇌에 있어서 잠깐 동안의 허혈성 자극을 주는 허혈성 전처치는 이어지는 장기간의 허혈성 손상을 이길 수 있는 내성을 유발하는 것으로 알려져 있다. 본 연구는 돼지 모델을 이용하여 이러한 허혈성 내성이 척추신경의 허혈성 전처치를 통하여도 생길 수 있는지의 여부를 알아보고자 하였다. 대상 및 방법 : 실험은 세 군으로 나뉘어 시행되었다 : sham 군(n=3), 대조군(n=6)과 허혈성 전처치군(n=8). Sham 군에서는 척추 신경의 허혈성 손상 없이 좌측 개흉술 만을 시행하였다. 대조군과 허혈성 전처치군은 30분간의 대동맥 차단을 통한 척추신경의 허혈성 손상이 가해졌다. 하지만 허혈성 전처치군은 48시간전에 20분간의 허혈성 자극이 선행되었다. 24시간 후에 신경학적 검사를 시행하였으며, 조직 병리와 MPA (malonedialdehyde) spectrophotometry 검사를 위하여 척추 신경을 취득하였다. 결과: 허혈성 손상 24시간 후에 행하여진 신경학적 검사에서 대조군과 허혈성 전처치군 사이에 통계학적으로 유의한 차이가 있었다(p=0.028). 조직병리와 MDA 검사에서는 통계적으로 유의한 차이를 얻을 수 없었으나, MDA 검사상 경계선상의 통계적 유의성은 보이고 있었다. 결론: 본 돼지 실험 연구를 통해 비록 실험 동물들이 걷거나 설 수 있을 정도의 완전한 척추신경의 회복을 보이지는 못했으나, 허혈성 전처치가 척추신경의 30분간의 허혈성 손상에 대하여 견딜 수 있는 내성을 유발시키는 것을 알 수 있었다. 허혈성 전처치가 기존의 척추신경의 허혈성 손상을 보호하기 위한 방법들과 병행될 때 상승 보호 효과를 얻을 수 있으리라 기대되며, 이에 대한 실험들이 뒷받침되어야 할 것이다.35.81 $\textrm{mm}^2$(Level 1), 181.88$\pm$34.74 $\textrm{mm}^2$(Level 2)로 두 위치에서 단면적은 남녀간에 유의한 차이가 있었다(p 0.05). 기관의 각각의 위치에서 내경과 단면적은 연령군에 따라 고연령층에서 증가하는 추세를 나타내었으나 통계적인 의미는 없었다. 결론: 한국 정상 성인의 기관내경과 단면적의 크기는 성별에 따라 통계적으로 유의한 차이가 있었으나 연령에 따른 차이는 없었고, 전산화 단층촬영은 기관의 내경과 단면적의 크기를 얻는데 비교적 정확하고 안전한 방법이라 생각된다.의한 약물학적 전처치는 재관류 후 심근기능 회복에 유익한 효과를 나타냈으며, 이러한 전처치 효과는 교감신경계 신경전달물질의 고갈이나 $\alpha$1-수용체 차단제에 의해 소멸되는 것으로 보아 전처치에 의한 심근보호효과는 교감신경계 전달물질 및 $\alpha$1-수용체를 통해 유도됨을 알 수 있다.380$\pm$71 mL, p=0.05).방 및 치료에 도움이 될 수 있는 물질을 개발할 가치가 있다고 사료된다을 공급한 대조구에 비해 높았다. 어미의 성 성숙 및 산란은 두 번의 실험에서 대조구보다 저염분구에서 원만히 이루어졌다. 암컷 성숙 개체의 경우 1차 실험은 대조구 6마리, 저염분구 12마리였으며, 2차 실험은 대조구 5마리, 저염분구 12마리였으며, 2차 실험은 대조구 5마리, 저염분구 14마리로서 성숙유도에 있어 염분의 조절에 의한 성숙이 이루어진 것을 알 수 있다. 산란 시기는 1차 실험에서 대조구나 저염분구의 산란 개시 시점이 거의 동일한 데 비해, 2차 실험에서는 저염분구가 대조구에 비해 대략 20일 정도 빠르게 나타났다. 또한 산란에 가입한 암컷 어미의 개체수도 두 차례의 실험 모두 저염분구가 많았다. 또한

• Journal of Korean Neurosurgical Society
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• 제63권2호
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• pp.153-162
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• 2020

Spinal cord injury (SCI) is one of the most devastating conditions and many SCI patients suffer neurological sequelae. Stem cell therapies are expected to be beneficial for many patients with central nervous system injuries, including SCI. Adult stem cells (ASCs) are not associated with the risks which embryonic stem cells have such as malignant transformation, or ethical problems, and can be obtained relatively easily. Consequently, many researchers are currently studying the effects of ASCs in clinical trials. The environment of transplanted cells applied in the injured spinal cord differs between the phases of SCI; therefore, many researchers have investigated these phases to determine the optimal time window for stem cell therapy in animals. In addition, the results of clinical trials should be evaluated according to the phase in which stem cells are transplanted. In general, the subacute phase is considered to be optimal for stem cell transplantation. Among various candidates of transplantable ASCs, mesenchymal stem cells (MSCs) are most widely studied due to their clinical safety. MSCs are also less immunogenic than neural stem/progenitor cells and consequently immunosuppressants are rarely required. Attempts have been made to enhance the effects of stem cells using scaffolds, trophic factors, cytokines, and other drugs in animal and/or human clinical studies. Over the past decade, several clinical trials have suggested that transplantation of MSCs into the injured spinal cord elicits therapeutic effects on SCI and is safe; however, the clinical effects are limited at present. Therefore, new therapeutic agents, such as genetically enhanced stem cells which effectively secrete neurotrophic factors or cytokines, must be developed based on the safety of pure MSCs.

• International Journal of Contents
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• 제8권1호
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• pp.74-81
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• 2012

The aim is to investigate the analgesic effect of transcranial direct current stimulation(tDCS) on central neuropathic pain(CNP) in spinal cord contusive rat model. Twenty Sprague-Dawley rats($250{\pm}50$ g, male) were used. Thoracic spinal cord(T10) was contused using New York University(NYU) spinal cord impactor. The animals were randomly assigned to two groups; GroupI: Non-treatment after SCI induction(n=10), GroupII: application of tDCS(0.1 mA, 20 min/time, 2 times/day, 5 days/6week) after SCI induction(n=10). Assess the effect of tDCS using the Basso Beattie Bresnahan(BBB) locomotor rating scales, Touch $test^{TM}$ sensory evaluator(TTSE), Plantar test$^{\circledR}$after contusion at the $2^{nd}$, $3^{rd}$, $4^{th}$, $5^{th}$, $6^{th}$ week and the immunohistochemistric response of c-fos in the thalamus, cerebral cortex after contusion at the $3^{rd}$, $6^{th}$ week after SCI. The scores of BBB scales were significantly different from $3^{rd}$week. TTSE were different significantly over time, but there were no differences at each evaluation times on between-measure time effects. Plantar test were different significantly over time and there were difference at the $4^{th}$, $6^{th}$ week after SCI on between-measure time effects. Also, immunohistochemistric response of c-fos was reduced significantly from $3^{rd}$, $6^{th}$ week after SCI in tDCS group compared with control group in thalamus and cortex. These results identified that tDCS of non-invasive therapeutic method may have beneficial analgesic effect on CNP after SCI with behavioral test and immunohistochemical test.

• The Journal of Korean Physical Therapy
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• 제23권2호
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• pp.45-52
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• 2011

Purpose: The purpose of this study was to investigate the effect of electroacupuncture on NeuN expression in ventral horn motor neurons of spinal cord, changes in pain thresholdchanges in motor function in rats with partially dissected sciatic nerves. Method: A total of 120 male Sprague-Dawley rats were randomly divided into two groups, a control group and a group administered electroacupuncture at ST36, LI11 and SP9 with 120 Hz and 0.5 mA. Animals were sacrificed on days 1, 3, 7, 14 and 28 after nerve injury (the sciatic nerve was partially dissected). The pain threshold was recorded by an Analgesia? meter and a BBB? score was calculated for motor function. After preparing lumbar spinal cord slide sections, they were immunostained with NeuN antisera (1:2,500). Results: The numbers of NeuN immunoreactive neuronsin the electroacupuncture group was increased compared to the control group. The numbers of NeuN immunoreactive neurons on days 14 and 28 day were different (p<0.05), as were the numbers on days 3 and 7 (p<0.01). The pain threshold BBB score for the electroacupuncture group was higher than for controls. Conclusion: The increase in pain threshold, BBB-score and number of NeuN immunoreactive neurons inventral horn motor neurons of spinal cord in rats withnerve dissection showed that electroacupuncture can attenuate pain transduction and increase motor function. Also, NeuN was a good marker for identifying the degree of nerve cell loss after nervous system injury.