• Journal of Korean Neurosurgical Society
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• 제59권4호
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• pp.334-340
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• 2016

Objective : The aim of our study was to evaluate the neuroprotective functions of the combination therapy using methylprednisolone (MP) and tranilast (TR) after spinal cord injury (SCI) in adult rats. Methods : Spinal cord compression injury model was achieved using Yasargil aneurysm clip. Rats were divided into control group, MP group, TR group, and combination therapy group using TR and MP. Rat models were assessed for locomotor functional recovery using Basso, Beattie, and Bresnahan (BBB) score, spinal cord water content and myeloperoxidase (MPO) activity 24 hours post SCI, haematoxylin and eosin staining and glial fibrillary acid protein (GFAP) staining at 7 and 14 days post SCI. Results : The spinal cord water content and MPO activity in the combination therapy group was significantly lower than the control group and the individual therapy groups p<0.05. The combination therapy group had significantly higher BBB scores than control group and individual therapy groups (p<0.05). At one week after SCI, GFAP expression in the combination group was significantly lower than the control group (p<0.05) but there was no significant difference compared to the individual therapy groups (p>0.05). At 2 weeks after SCI there was a slight decrease in GFAP expression compared to the first week but the difference was not statistically significant (p>0.05), GFAP expression between the groups was not statistically significant p>0.05. Conclusion : Combining MP and TR is therapeutically more effective in improving functional recovery, inhibiting inflammation and glial scar formation after acute SCI.

• Advances in Traditional Medicine
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• 제7권5호
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• pp.556-563
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• 2008

Peripheral nerve injuries are a commonly encountered clinical problem and often result in a chronic pain and severe functional deficits. The expression of c-Fos is sometimes used as a marker of increased neuronal activity. We have prepared the aqueous extract of amygdalin from Armeniacae semen for pain control. In the present study, we investigated the effects of amygdalin on the recovery rate of the locomotor function and on the expression of c-Fos in the ventrolateral periaqueductal gray (vlPAG) region following sciatic crushed nerve injury in rats. Walking track analysis for the evaluation of functional recovery and immunohistochemistry for the c-Fos expression were used in this study. In the present results, characteristic gait change with dropping of the sciatic function index (SFI) was observed and c-Fos expression in the vlPAG was suppressed following sciatic crushed nerve injury in rats. Amygdalin enhanced SFI value and restored c-Fos expression in the vlPAG to the control value. The present our study indicated that amygdalin activates neurons in the vlPAG, and it facilitates functional recovery following peripheral nerve injury.

• 동의생리병리학회지
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• 제24권3호
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• pp.476-483
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• 2010

The present study was performed to investigate the putative anxiolytic-like effects of the aqueous extract of the roots of Scrophularia buergeriana (SB-W) using elevated plus-maze (EPM) and hole-board apparatus in mice. SB-W was orally administered at doses of 50, 100, 200 or 400 mg/kg to ICR mice, 1 h before the behavioral evaluation. Control group were administered with an equal volume of saline, and positive control group with buspirone (2 mg/kg, i.p.). The administration of SB-W significantly increased the percentage of time spent in open arms and entries into the open arms of the EPM compared with saline-treated control group (P < 0.05). Futhermore, those anxiolytic-like activities of SB-W were antagonized by flumazenil (a $GABA_A$ antagonist, 10 mg/kg), but not by WAY-100635 (a 5-$HT_{1A}$ antagonist, 0.3 mg/kg). Moreover, there were no changes in the locomotor activity and myorelaxant effects in any group compared with saline-treated control group. In the hole-board test, the administration of SB-W (200 and 400 mg/kg) significantly increased the number of head-dipping compared with saline-treated control group (P < 0.05). Therefore, these findings suggest that Scrophularia buergeriana promotes the anxiolytic-like activity mediated by GABAergic nervous system in mice.

• Biomolecules & Therapeutics
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• 제7권3호
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• pp.271-277
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• 1999

Safety evaluation of LB71350, a new HIV-1 protease inhibitor, was performed in mice, rats and dogs. For the general behavior of mice, LB71350 at an oral dose of 200 mg/kg did not show any significant effects on muscle tone and locomotor activity. In terms of central nervous system, at oral doses of 200 mg/kg and 1000 mg/kg, LB71350 inhibited acetic acid-induced pain response approximately 41% and 83% of control. respectively. At oral doses of 200 mg/kg and 500 mg/kg, it reduced the rectal body temperature in rats. Pentylenetetrazole-induced seizure in mice was slightly potentiated by oral administration of LB71350 at doses ranging from 200 mg/kg to 1000 mg/Ag. Single or five day treatment of LB71350 doubled the hexobarbital- induced sleeping time in mice at oral doses ranging from 50 mg/kg to 500 mg/kg. It did not cause any effects on gastric secretion and acidity in rat at oral doses of 200 mg/kg and 1000 mg/kg and also it did not change intestinal motility in mice up to 1000 mg/kg. Blood coagulation indices such as prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin time (TT) in rats were not affected by the treatment of LB71350 up to 500 mg/kg. LB71350 caused no significant effects on the cardiac output, stroke volume, heart rate, and mean blood pressure when infused intravenously to the anesthetized rats and dogs. Taken together, LB71350 at high oral doses caused significant pharmacological effects on the central nervous system and the hexobarbital-induced sleeping time.

• 대한약침학회지
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• 제21권4호
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• pp.277-283
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• 2018

Objectives: Ethanol withdrawal following its chronic use is a serious outcome and challenging to treatment. The chronic use of ethanol induces a progressive neuroplasticity in different reigns of brain. In this study we evaluated the effects of aqueous extract of Crocus sativus L. (saffron) and its active compound, crocin, on the withdrawal behavior induced after repeated administration of ethanol, in two regimens of prophylactic (administration of drugs concomitant with the induction of dependence) and treatment (administration of drugs during the period of ethanol withdrawal) in mice which received ethanol. Methods: Ethanol dependence was induced by oral administration of 10% v/v ethanol (2 g/kg) for 7 days. The aqueous extracts of saffron (40, 80 and 160) and crocin (10, 20 and 40 mg/kg) were administered to mice in two regimens of prophylactic (along with ethanol) and treatment (during withdrawal period). Diazepam (1 mg/kg) was used as a positive control. Six hours after discontinuation of the ethanol, seizure was evaluated by the sub-convulsive dose of pentyleneltetrazole (PTZ) (30 mg/kg). The open field test and Rota rod test were used for evaluation of locomotor activity and motor incoordination, respectively. Results: Both extracts and crocin increased the number of crossed lined in the open field test. PTZ kindling seizure was inhibited in animals received extract (80 and 160 mg/kg) in both regimens. Motor incoordination was only improved following administration of crocin. Conclusion: The aqueous extract of saffron and crocin can be considered as safe agents and reliable alternative to diazepam in management of ethanol withdrawal syndrome.

• Journal of Acupuncture Research
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• 제39권4호
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• pp.310-316
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• 2022

Background: Verbenalin is an iridoid glucoside, which is among the active components of some medicinal herbs such as Verbena officinalis Linn, and Cornus officinalis Siebold and Zucc. Previous studies have confirmed the antioxidant activity and neuroprotective potential of verbenalin. To confirm the safety of verbenalin, an approximate lethal dose was determined based on a single oral dose toxicity study. Methods: Institute of Cancer Research mice were randomly assigned to three verbenalin exposure groups (250, 500, and 1,000 mg/kg) and a control group (5% methylcellulose solution). There were (5 male and 5 female mice per group). Mortality, clinical signs, and body weight were monitored for 14 days, and necropsies were conducted. Results: No mortalities were observed in the control group or the verbenalin 250 mg/kg group, whereas mortalities were observed in the 500 mg/kg and 1,000 mg/kg verbenalin groups. During the observation period, stool abnormalities such as mucous stools were observed. Clinical signs such as loss of locomotor activity were observed in the 500 mg/kg and 1,000 mg/kg verbenalin groups. During the study period, significant changes in body weight were observed in the 500 mg/kg and 1,000 mg/kg verbenalin groups; however, no gross abnormalities were observed at necropsy. Overall, no toxicity was found in the 250 mg/kg group. Conclusion: The approximate lethal dose of verbenalin was estimated to be 500 mg/kg. For a more accurate assessment of the safety of verbenalin, other types of studies such as repeated-dose toxicity studies should also be conducted.

• Clinical and Experimental Pediatrics
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• 제48권4호
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• pp.425-432
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• 2005

목 적 : 폴리글루타민 질환은 해당 발현단백질의 연속되는 글루타민 아미노산 서열이 신장되기 때문에 일어나는 질환군이다. 현 연구는 폴리글루타민 질환 형질전환 초파리 모델들이 환자들 에서와 유사한 장애를 나타내는지 확인하기 위해 수행되었다. 방 법 : 폴리글루타민 질환 (SCA3) 형질전환 초파리를 대상으로 벽을 기어오르는 운동 능력을 검사하였다. 또한 유전학적인 방법을 통해서 아폽토시스를 억제하는 bcl-2 유전자와 화학적 샤페론이 뇌신경의 퇴행에 어떤 영향을 미치는지 확인하였으며 향후의 연구를 위해 척수소뇌 운동실조증 타입 2 (SCA2) 질환을 발현하는 형질전환 초파리를 생산하였다. 결 과 : SCA3 형질전환 초파리에서 신장된 폴리글루타민 배열을 지니는 질환성 초파리의 경우 신경계에서 해당 단백질을 발현하였을 경우 전형적인 운동 능력 상실을 나타냈다. 아폽토시스를 억제하는 유전자인 bcl-2를 함께 발현했을 경우, 신장된 단백질의 유독한 영향을 약화시키지 못했지만, 화학적 샤페론인글리세롤의 경우 적어도 눈에서의 유독한 영향은 억제하는 것으로 보인다. 본 연구진에 의해 개발된 SCA2 형질전환 초파리의 경우 유해 단백질의 발현 정도가 낮아서 정확한 분석이 어려웠다. 결 론 : SCA3 형질전환 초파리는 환자들에서 발견되는 운동실조증을 보였다. 글리세롤과 같은 화학적 샤페론이 현재 치료가 전무한 이 종류의 질환군의 치료에 효과적일 것으로 사료된다.

• Journal of Chest Surgery
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• 제49권4호
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• pp.232-241
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• 2016

Background: Paraplegia is a devastating complication following operations on the thoracoabdominal aorta. We investigated whether histidine-tryptophan-ketoglutarate (HTK) solution could reduce the extent of ischemia/reperfusion (IR) spinal cord injuries in a rat model using a direct delivery method. Methods: Twenty-four Sprague-Dawley male rats were randomly divided into four groups. The sham group (n=6) underwent a sham operation, the IR group (n=6) underwent only an aortic occlusion, the saline infusion group (saline group, n=6) underwent an aortic occlusion and direct infusion of cold saline into the occluded aortic segment, and the HTK infusion group (HTK group, n=6) underwent an aortic occlusion and direct infusion of cold HTK solution into the occluded aortic segment. An IR spinal cord injury was induced by transabdominal clamping of the aorta distally to the left renal artery and proximally to the aortic bifurcation for 60 minutes. A neurological evaluation of locomotor function was performed using the modified Tarlov score after 48 hours of reperfusion. The spinal cord was harvested for histopathological and immunohistochemical examinations. Results: The spinal cord IR model using direct drug delivery in rats was highly reproducible. The Tarlov score was 4.0 in the sham group, $1.17{\pm}0.75$ in the IR group, $1.33{\pm}1.03$ in the saline group, and $2.67{\pm}0.81$ in the HTK group (p=0.04). The histopathological analysis of the HTK group showed reduced neuronal cell death. Conclusion: Direct infusion of cold HTK solution into the occluded aortic segment may reduce the extent of spinal cord injuries in an IR model in rats.