• Anatomy and Cell Biology
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• 제50권3호
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• pp.207-213
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• 2017

Glycogen synthase kinase $(GSK)-3{\beta}$ and related enzymes are associated with various forms of neuroinflammation, including spinal cord injury (SCI). Our aim was to evaluate whether lithium, a non-selective inhibitor of $GSK-3{\beta}$, ameliorated SCI progression, and also to analyze whether lithium affected the expression levels of two representative $GSK-3{\beta}$-associated molecules, nuclear factor erythroid 2-related factor-2 (Nrf-2) and heme oxygenase-1 (HO-1) (a target gene of Nrf-2). Intraperitoneal lithium chloride (80 mg/kg/day for 3 days) significantly improved locomotor function at 8 days post-injury (DPI); this was maintained until 14 DPI (P<0.05). Western blotting showed significantly increased phosphorylation of $GSK-3{\beta}$ (Ser9), Nrf-2, and the Nrf-2 target HO-1 in the spinal cords of lithium-treated animals. Fewer neuropathological changes (e.g., hemorrhage, inflammatory cell infiltration, and tissue loss) were observed in the spinal cords of the lithium-treated group compared with the vehicle-treated group. Microglial activation (evaluated by measuring the immunoreactivity of ionized calcium-binding protein-1) was also significantly reduced in the lithium-treated group. These findings suggest that $GSK-3{\beta}$ becomes activated after SCI, and that a non-specific enzyme inhibitor, lithium, ameliorates rat SCI by increasing phosphorylation of $GSK-3{\beta}$ and the associated molecules Nrf-2 and HO-1.

• 약학회지
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• 제44권6호
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• pp.499-504
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• 2000

We previously demonstrated that 6-paradol, a compound structurally related to capsaicin, showed to produce prolonged analgesia in experimental animals. The effects of 6-paradol on the release of adenosine were investigated in the rat spinal cord synaptosomes by high performance liquid chromatography. In the presence of $Ca^{++}$, adenosine was released from synaptosomes of rat spinal cord by 6-paradol and capsaicin in a dose dependent manner. Nifedifine, L-type voltage sensitive calcium channel blocker, was found to be ineffective in releasing adenosine by $10\;{\mu}M$ 6-paradol. After exposure to $10\;{\mu}M$ capsazepine, a novel capsaicin selective antagonist, the level of adenosine evoked by $10\;{\mu}M$ 6-paradol was decreased by 75%, and that evoked by $10\;{\mu}M$ capsaicin was blocked completely. These results suggest that the analgesic effect of 6-paradol might be mediated by the vanilloid (capsaicin) sensitive pathway, or the direct binding to the vanilloid receptor.

• Journal of Pharmaceutical Investigation
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• 제9권2호
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• pp.22-30
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• 1979

Effects of Akebiae Lignum, whose scientific name is Akebia quinata Decaisne, on the blood pressure were investigated with EtOH extract in whole and spinal rabbits. Akebia Lignum EtOH extract (AEE), when given intravenously, produced a fall in blood pressure not only in whole rabbit but also in spinal rabbit and AEE administered into a lateral cerebral ventricle of whole rabbit did not elicit a fall in blood pressure. The depressor responses of the whole rabbit to intravenous AEE were weakened by treatment of the animals with atropine and chlorisondamine but not by vagotominijation, phentolamine avil, and then the depressor action causing by AEE in the whole rabbit was not affected by pretreatment of physostigmine which is cholinesterase inhibitor and of hemicholinium which blocks acetylcholine synthesis by interfering with choline uptake in nerves. These observations suggest that the hypotensive action of AEE of which component is not affected by cholinesterase is due to direct action at parasympathetic receptor.

• The Korean Journal of Physiology and Pharmacology
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• 제12권5호
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• pp.245-251
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• 2008

Single-channel recordings of TASK-1 and TASK-3, members of two-pore domain $K^+$ channel family, have not yet been reported in dorsal root ganglion (DRG) neurons, even though their mRNA and activity in whole-cell currents have been detected in these neurons. Here, we report single-channel kinetics of the TASK-3-like $K^+$ channel in DRG neurons and up-regulation of TASK-3 mRNA expression in tissues isolated from animals with spinal cord injury (SCI). In DRG neurons, the single-channel conductance of TASK-3-like $K^+$ channel was $33.0{\pm}0.1$ pS at - 60 mV, and TASK-3 activity fell by $65{\pm}5%$ when the extracellular pH was changed from 7.3 to 6.3, indicating that the DRG $K^+$ channel is similar to cloned TASK-3 channel. TASK-3 mRNA and protein levels in brain, spinal cord, and DRG were significantly higher in injured animals than in sham-operated ones. These results indicate that TASK-3 channels are expressed and functional in DRG neurons and the expression level is up-regulated following SCI, and suggest that TASK-3 channel could act as a potential background $K^+$ channel under SCI-induced acidic condition.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 1990년도 Proceedings of International Symposium on Korean Ginseng, 1990, Seoul, Korea
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• pp.36-44
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• 1990

The analgesic effect of morphine was antagonized and the development of tolerance was suppressed by the modification of the neurologic function in the animals treated with ginseng saponins. The activation of the spinal descending inhibitory systems as well as the supraspinal structures by the administration of morphine was inhibited in the animals treated with ginseng saponins intracerebrally or intrathecally The development of morphine tolerance and dependence, and the abrupt expression of naloxone induced abstinence syndrome were also inhibited by ginsenoside Kbl , Rba, Rgl and Re. These results suggest that ginsenoside Kbl, Rba, Rgl and Re are the bioactive components of panax ginseng on the inhibition of the development of morphine tolerance and dependence, and the inhibition of abrupt abstinence syndrome. In addition, further research on the minor components of Panax ginseng should be investigated. A single or daily treatment with ginseng saponins did not induce any appreciable changes in the brain level of monoamines at the various time intervals and at the various day intervals, respectively The inhibitory or facilitated effects of ginseng saponins on electrically evoked contractions in guinea pig ileum (U-receptor) and mouse was definers (5·receptor) were not mediated through opioid receptors. The antagonism of a x receptor agonist, U-, iO.488H was also not mediated through opioid receptors in the animals treated with ginseng saponins, bolt mediated through serotonergic mechanisms. Ginseng saponins inhibited morphine S-dehydrogenase that catalyzed the production of morphine from morphine, and increased hepatic glutathione contents for the detoxification of morphine. This result suggests that the dual action of the above plays an important role in the inhibition of the development of morphine tolerance and dependence.

• Journal of Korean Neurosurgical Society
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• 제46권1호
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• pp.1-4
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• 2009

Objective: To report an unsuspected adaptive plasticity of single upper motor neurons and of primary motor cortex found after microsurgical connection of the spinal cord with peripheral nerve via grafts in paraplegics and focussed discussion of the reviewed literature. Methods: The research aimed at making paraplegics walk again, after 20 years of experimental surgery in animals. Amongst other things, animal experiments demonstrated the alteration of the motor endplates receptors from cholinergic to glutamatergic induced by connection with upper motor neurons. The same paradigm was successfully performed in paraplegic humans. The nerve grafts were put into the ventral-lateral spinal tract randomly, with out possibility of choosing the axons coming from different areas of the motor cortex. Results: The patient became able to selectively activate the re-innervated muscles she wanted without concurrent activities of other muscles connected with the same cortical areas. Conclusion: Authors believe that unlike in nerve or tendon transfers, where the whole cortical area corresponding to the transfer changes its function a phenomenon that we call "brain plasticity by areas". in our paradigm due to the direct connection of upper motor neurons with different peripheral nerves and muscles via nerve grafts motor learning occurs based on adaptive neuronal plasticity so that simultaneous contractions of other muscles are prevented. We propose to call it adaptive functional "plasticity by single neurons". We speculate that this phenomenon is due to the simultaneous activation of neurons spread in different cortical areas for a given specific movement, whilst the other neurons of the same areas connected with peripheral nerves of different muscles are not activated at the same time. Why different neurons of the same area fire at different times according to different voluntary demands remains to be discovered. We are committed to solve this enigma hereafter.

• The Korean Journal of Pain
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• 제11권1호
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• pp.1-6
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• 1998

Background: The role of nitric oxide(NO) in analgesia from opioids is controversial. On the one hand, IV morphine analgesia is enhanced by IV injection of NO synthase inhibitors. On the other hand, IV morphine results in increased release of NO in the spinal cord. There have been no behavioral studies examining the interaction between IV morphine and intrathecal injection of drugs which affect NO synthesis. Method: Rats were prepared with chronic lumbar intrathecal catheters and were tested withdrawal latency on the hot plate after 3~5 days of surgery. Antinociception was determinined in response to a heat stimulus to the hind paw before and after IV injection of morphine, 2.5 mg/kg. Twenty minutes after morphine injection, rats received intrathecal injection of saline or the NO synthase inhibitors, L-NMMA or TRIM, the NO scavenger, PTIO, or the NO synthase substrate, L-Arginine. Intrathecal injections, separated by 15 min, were made in each rats and measurements were obtained every 5 min. Result: Mophine produced a 60~70% maximal antinociceptive response to a heat stimulus in all animals for 60 min in control experiments. Intrathecal injection of idazoxane decreased antinociception of IV morphine. The NO synthase inhibitors and the NO scavenger produced dose-dependent decreases in antinociceptive effect of morphine, whereas saline as a control group and L-Arginine as the NO substrate had no effect on antinociception of morphine. Conclusion: The present study supports the evidences that systemic morphine increase the nitrite in cerebrospinal fluid and dorsal horn. These data suggest that the synthesis of NO in the spinal cord may be important to the analgesic effect of IV morphine and increased NO in spinal cord has different action from the supraspinal NO.

• Journal of Chest Surgery
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• 제41권4호
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• pp.405-416
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• 2008

배경: 흉부 및 흉복부 대동맥의 수술 중 대동맥 차단은 허혈성 척수 손상에 의한 하반신 마비와 같은 심각한 합병증을 유발할 수도 있어 수술 중 허혈성 척수손상을 예방하기 위한 여러 방법의 연구가 계속 되고 있다. 최근에 허혈성 대뇌 손상 모델에서 신경조직의 막전위 의존성 나트륨채널 길항제가 대뇌 보호 효과가 있다는 보고가 있다. 본 연구는 토끼의 허혈성 척수손상 모델에서 나트륨채널 길항제인 페니토인과 저체온의 척수보호효과를 비교해 보고자 시행되었다. 대상 및 방법: 뉴질랜드산 토끼의 신동맥직하부에서 복부대동맥을 25분간 차단하는 방식으로 척수허혈을 유도하였으며 각 군당 8마리씩 네 군으로 나누었다. 대조군과(S39) 저체온군은(S37) 대동맥 차단시간 동안 직장온도를 각기 $39^{\circ}C$와 $37^{\circ}C$로 일정하게 유지하면서 $22^{\circ}C$ 생리적 식염수만 2 mL/min의 속도로 연속 주입하였으며, 정상체온 및 저체온 페니토인 군은(P39, P37) 앞의 두 군과 동일한 방법으로 하되 생리적 식염수에 페니토인을 녹여 주입하였다(100 mg/50 mL). 수술 후 24시간 및 72시간이 경과한 다음 Tarlov scoring을 통해 신경학적 평가를 시행하였고 마지막 평가 후에는 객관적으로 신경손상의 정도를 정량화하기 위해 척수를 고정 처리하였다. 결과: 페니토인의 역행성 주입에 따른 심각한 문제는 없었으며 대조군에(S39) 속한 모든 동물은 완전 또는 심한 하반신 마비 소견을 보였다. 페니토인과(P39) 저체온(S37)군 모두 대조군에 비해 신경학적 평가는 유사한 정도로 우수한 결과를 보였다(p<0.05). 조직 병리학적 검사 결과, 대조군에 속한 모든 동물은 척수 회백질에서 심한 신경조직 괴사 때 보이는 전형적인 특징을 보여주었으며, TUNEL 염색에 양성인 신경세포도 높은 빈도로 관찰되었으나, 저체온 또는 페니토인 투여 군에서는 괴사현상이 유의한 정도로 감소하였으며, 상대적으로 매우 낮은 빈도의 TUNL 염색 양성세포가 관찰되었다(p<0.05). 그러나 저체온과 페니토인을 병용했을 때의 부가적인 척수보호효과를 조사해 본 결과 신경학적 평가와 조직병리학적 결과 모두 유의한 수준의 부가적인 효과는 없었다. 걸론: 결론적으로, 토끼의 허혈성 척수 손상 모델을 이용하여 페니토인과 저체온의 신경보호효과를 알아본 결과 신경학적 평가와 조직병리학적 검사 결과 모두 부가적인 효과는 보여주지 못했지만 각각의 경우 유사한 정도의 신경보호효과를 보여주었다.

• 한국임상수의학회지
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• 제18권4호
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• pp.315-323
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• 2001

본 실험에서는 인공적으로 척수관의 20-50%를 차지하는 이물을 척수관내에 삽입한 후 이물제거 시기에 따라 somatosensory evoked potentials (SEPs) 변화상을 임상증상과 척수조영술을 이용하여 비교 관찰하였다. 실험군은 척수관의 50%를 차지하는 이물을 삽입하여 1주일 후에 제거한 군(II군), 2일 수에 제거한 군(III군), 또 척수관의 20%를 차지하는 이물을 삽입하여 1주일 후에 제거한 군(IV군), 2일 후에 제거한 군(V군), 8주 계속 유지한 군(VI군) 그리고 대조군으로 laminectomy만을 실시한 군(I군)으로 나누었다. 척수관 직경의 50%를 차지하는 큰 이물을 삽입하여 2일간 유지하였다가 제거한 후 관찰한 군(III군), 척수관 직경의 20%를 차지하는 작은 이물을 삽입하여 1주일간 유지하였다가 제거한 후 관찰한 군(IV군), 작은 이물을 삽입하여 2일간 유지하였다가 제거한 후 관찰한 군(V군)에서는 SEPs latency와 임상증상에서 거의 이상이 나타나지 않았다. 작은 이물을 8주간 계속 유지한 군(VI군)에서는 SEPs latency에서는 약간의 이상을 보였으나 임상증상에서 거의 이상이 나타나지 않았다. 척수압박 후 제거한 각각의 군에서 SEPs latency와 임상증상은 비슷한 회복추이를 보였다. 그러나 척수관 직경의 50%를 차지하는 큰 이물을 삽입하여 1주일간 유지하였다가 제거한 후 관찰한 군(II군)에서는 TN1의 SEPs latency는 기록되지 않았으며, 임상적으로 신경증상을 나타내었다. III, Iv 및 V 군에서 TP1과 TN1(T11과 T12사이)은 이물 삽입 직후에는 비정상적으로 기록되었고 처음으로 TP1과 TN1 값이 기록된 날은 이물을 삽입하였다가 제거한 후 각각 6일, 9.5일 및 3.5일째였다. VI군에서 TN1의 유발전위는 이물삽입 후 7.7일째부터 기록되었고 34일째에 정상적인 파형을 보였다. II군에서 TN1의 유발전위는 이물을 삽입하였다가 제거한 후 8주째 까지 기록되지 않았다. I군에서 TN1 값은 laminectomy 후 1일째에 처음으로 기록되었다.

• The Korean Journal of Physiology
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• 제21권1호
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• pp.67-77
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• 1987

Effect of intravenously injected clonidine on the flexion reflex was studied in 15 decerebrated and spinalized cats. The flexion reflex was elicited by electrical stimulation of the tibial nerve or the common peroneal nerve and it was recorded as single unit activity from filaments of the L6 or L7 ventral roots. In order to obtain the late flexion reflex discharges, $A{\delta}$ and C afferent fibers were stimulated with single or train electrical pulses respectively. The flexion reflex, especially the late component, was markedly inhibited after intravenous administration of clonidine. The clonidine-induced inhibition of the flexion reflex was compared before and after treatment of the animals respectively with yohimbine and naloxone. The inhibitory effect on the flexion reflex of clonidine was not altered by naloxone, a ${\mu}-opioid$ receptor blocker, whereas it was completely blocked by yohimbine, an ${\alpha}_2-adrenergic$ antagonist. These results indicate that clonidine inhibits the flexion reflex through excitation of ${\alpha}_2-adrenoceptors$ even at the spinal cord level.