• Biomolecules & Therapeutics
• /
• 제13권1호
• /
• pp.35-40
• /
• 2005

This study was performed to investigate the regulatory mechanism of cerebral blood flow of adenosine A$_{2B}$ receptor agonist in the rats, and to define whether its mechanism is mediated by adenylate cyclase, guanylate cyclase and potassium channel. In pentobarbital-anesthetized, pancuronium-paralyzed and artificially ventilated male Sprague-Dawley rats, all drugs were applied topically to the cerebral cortex. Blood flow from cerebral cortex was measured using laser-Doppler flowmetry. Topical application of an adenosine A$_{2B}$ receptor agonist, 5'-N-ethylcarboxamidoadenosine (NECA; 4 umol/I) increased cerebral blood flow. This effect of NECA (4 umol/I) was not blocked by pretreatment with adenylate cyclase inhibitor, MDL-12,330 (20 umol/I). But effect of NECA (4 umol/I) was blocked by pretreatment with guanylate cyclase inhibitor, LY-83,583 (10 umol/I) and pretreatment with ATP-sensitive potassium channel inhibitor, glipizide (5 umol/I). These results suggest that adenosine A$_{2B}$ receptor increases cerebral blood flow. It seems that this action of adenosine A$_{2B}$ receptor is mediated via the activation of guanylate cyclase and ATP-sensitive potassium channel in the cerebral cortex of the rats.

• 약학회지
• /
• 제33권3호
• /
• pp.149-155
• /
• 1989

To predict the influence of carbon monoxide poisonining on cerebral energy metabolism, rats were exposed to 5000 ppm environment for 30 minutes. Carboxyhemoglobin (HBCO) saturation rate in this condition was 72% equally in male and female rats. Cerebral cortex in the rats showed lower level of ATP, glucose, creatine phosphate and higher level of lactate, pyruvate by anaerobic glycolysis. As for the levels of ATP, creatine phsphate and glucose, the cerebral cortex contents of them were larger in female rats of estrus than in male rats, whereas there was no difference between sexes in the levels of pyruvate and lactate. According to time passage from CO intoxication, the mode of changes in cerebral energy metabolite contents was similar in both sexes.

• 약학회지
• /
• 제36권3호
• /
• pp.278-284
• /
• 1992

This study was performed to investigate the effects of ginseng saponins on the cerebral energy metabolite's contents influenced by carbon monoxide(CO) intoxication. Each experimental group was divided young ($5{\sim}8$ weeks) and aged ($43{\sim}52$ weeks) rats, and they were exposed at 5,000 ppm CO (72%HbCO) for 30 min. One of the other groups was pretreated with ginseng saponins for 5 days before CO intoxication. The contents of cerebral energy metabolites in cerebral cortex, stratum and hypothalamus were measured. In cerebral cortex of both young and aged rats, the levels of ATP and creatine phosphate were significantly decreased, while those of lactate were significantly increased. There was no difference between the levels of cerebral energy metabolites of young and aged rats. Pretreatment of ginseng saponins before CO intoxication lowered decrease of the levels of cerebral energy metabolites and ATP levels were significantly recovered. On the other hands, contents of lactate in stratum and hypothalamus of young rats were significantly increased and the levels of ATP and creatine phosphate in stratum and hypothalamus were completely recovered at 2 weeks after CO intoxication. The results suggest that ginseng saponins have an ameliorating action against disturbance of the cerebral energy metabolites by CO intoxication.

• Biomolecules & Therapeutics
• /
• 제5권3호
• /
• pp.306-315
• /
• 1997

In order to investigate pharmacological properties of ι -muscone, effects of ι-muscone and musk on cerebral ischemia and central nervous system were compared. Cerebral ischemia insult was performed using unilateral carotid artery occlusion in Mongolian gerbils. The histological observations showed a preventive effect of the ι-muscone treatment with ischemia-induced brain damage. The ATP in brain tissue was decreased in vehicle-treated ischemic gerbils. This decrease was prevented by the ι-muscone treatment. In contrast to what was seen with ATP, the lactate and lipid peroxide were both elevated in vehicle-treated ischemic gerbils.˙ This elevation was prevented by the ι-muscone treatment. While ι-muscone had no effects on the hexobarbital-induced sleeping time and the convulsions induced by electric shock, pentetrazol and strychnine, it had effect on rotarod test and spontaneous activity test. Respiration rate and depth were increased by the ι-muscone treatment. Furthermore, ι-muscone showed anti-stress effect. Our findings suggest that the pharmacological profile of ι-muscone on cerebral ischemia and central nervous system are similar to that of musk.

• Journal of Korean Neurosurgical Society
• /
• 제29권6호
• /
• pp.719-724
• /
• 2000

Objectives : It has been reported that the presence of a pharmacologically inactive foreign substance, polystyrene latex bead, in subarachnoid space activates a non-specific immunological response and elicits arterial narrowing. Recently the activation of potassium($K^+$) channels may be of benefit in relieving cerebral vasospasm. The present study examined the effects of systemic administration of a ATP-sensitive $K^+$ channel activator, cromakalim, on the polystyrene latex bead-induced cerebral vasospasm. Methods : The spasm models similar to that caused by subarachnoid blood injection were created by injection of bead into rabbit cisterna magna. Intravenous injections of cromakalim were administered twice daily(bid) 30 minutes after induction of vasospasm. Animals were killed by perfusion-fixation 2 days after vasospasm. Basilar arteries were removed and sectioned, and the luminal cross-sectional areas were measured. Results : Injection of bead elicited an arterial constriction, reducing arterial diameter to 33.3% of resting tone. Cromakalim inhibited bead-induced constriction at a dose of 0.3mg/kg(Mann-Whitney test, p<0.01). Conclusion : These results support the concept that the cellular events triggered by inactivation of ATP-sensitive $K^+$ channels are responsible for the pathogenesis of vasospasm. The findings also indicate that cromakalim represents a potential therapeutic agents for the treatment of cerebral vasospasm.

• Biomolecules & Therapeutics
• /
• 제5권4호
• /
• pp.402-411
• /
• 1997

ln order to investigate pharmacological properties of New Woohwangchungsimwon Liquid (NCL) and Woohwangchungsimwon Liquid (CL), effects of NCL and CL on cerebral ischemia and central nervous system were compared. Cerebral ischemia insult was performed using unilateral carotid artery occlusion in Mongolian gerbils. The histological observations showed a preventive effect of NCL and CL treatments with ischemia-induced brain damage. The ATP in brain tissue was decreased in vehicle-treated ischemic gerbils. This decrease was prevented by CL treatment. In contrast to what was seen with ATP, the lactate and lipid peroxide were both elevated in vehicle-treated ischemic gerbils. This elevation was inhibited by NCL and CL treatments. While NCL and CL had no effects on the hexobarbital-induced sleeping time, they prevented the seizures induced by electric shock and pentetrazol. NCL and CL showed sedative effect in rotarod and spontaneous activity test. Respiration rate and depth were increased at the high dose of NCL and CL. Furthermore, NCL and CL showed anti-stress effect. Our findings suggest that the pharmacological profile of NCL on cerebral ischemia and central nervous system are similar to that of CL.

• Biomolecules & Therapeutics
• /
• 제7권1호
• /
• pp.79-88
• /
• 1999

In order to investigate pharmacological properties of New Wonbang Woohwangchungsimwon Liquid(NSCL) and Wonbang Woohwangchungsimwon Liquid(SCL), the effects of NSCL and SCL on cerebral ischemia and central nervous system were compared. Cerebral ischemia insult was performed using unilateral carotid artery occlusion in mongolian gerbils. The histological observations showed a preventive effect of NSCL and SCL treatments with ischemia-induced brain damage. The ATP in brain tissue was decreased in vehicle-treated ischemic gerbils. This decrease was prevented by NSCL and SCL treatment. In contrast to what was seen with ATP, lipid peroxide were elevated in vehicle-treated ischemic gerbils. This elevation was inhibited by NSCL and SCL treatments. While NSCL and SCL had no effects on the hexobarbital-induced sleeping time, they showed sedative effect in rotarod and spontaneous activity test. NSCL and SCL prevented the seizures induced by electric shock and strychnine, but the effect of NSCL was less than that of SCL. Furthermore, NSCL and SCL showed anti-stress effect. Our findings suggest that the pharmacological profiles of NSCL on cerebral ischemia and central nervous system are similar to those of SCL.

• 약학회지
• /
• 제38권1호
• /
• pp.57-66
• /
• 1994

We studied the effect of eicosanoids on the content of energy metabolites and the intrasynaptosomal $Ca^{++}([Ca^{++}]_i)$ concentration in cerebral ischemic rats. An ischemic model was made by bilateral carotid artery ligation (BCAL) and by incubation of synaptosomes under aglycemic and $N_2$ gas bubbling condition. The content of ATP, creatine phosphate and glucose decreased at 15 minutes after BCAL while that of lactate increased in male Wistar rats. Oral administration of EPA(100 mg/ml/Kg/day) or DHA(16 mg/ml/Kg/day) for 6 weeks improved both the decreases and the increase of the cerebral energy metabolites. In addition, the increase of $[Ca^{++}]_i$, under BACL was suppressed by EPA or DHA treatment. When the both Wistar rats and SHR were administered orally with EPA or DHA for 6 weeks, the effect on the increase of $[Ca^{++}]_i$ under ischemia by $N_2$ gas bubbling were protected. From these results, it may be that EPA or DHA treatment were greatly contributed to preservation of ischemic cerebral energy metabolism and $Ca^{++}$ concentration.

• Applied Microscopy
• /
• 제29권4호
• /
• pp.459-470
• /
• 1999

9, 10일 계배의 대뇌 신경세포 분화의 변화를 관찰하기 위하여 신경세포의 미세구조 변화를 전자현미경을 이용하여 관찰하였으며, 또한 대뇌 단백질, 탈수소효소의 활성도 및 ATP의 변화상을 분석한 결과는 다음과 같다. 대뇌 신경세포의 미세구조의 변화는 발생 9일 계배의 염색질은 핵질내에 비교적 고르게 분포해 있었으며 핵막은 2중막으로 아주 선명하게 구별되어 있음을 관찰할 수 있었다. 특히 조면소포체와 Golgi복합체가 잘 발달되어 있었으며, 또한 polysome이 관찰되었고 synaptic소포들이 산재되어 있었다. 10일 배양군의 계배의 신경세포는 염색질이 고루 분포해 있었으며 핵막을 뚜렷이 구분할 수 있었다. 세포질을 포함한 조면소포체와 mitochondria 그리고 Golgi 복합체가 비교적 잘 발달되어 있었다. 계배대뇌의 9일 배양군에서는 37개의 polypeptide band들이 분리되었고, 10일 배양군에서는 38개의 band가 생성되었다. 탈수소효소 활성도는 배양시간이 증가할 수록 증가하는 현상을 보였는데, LDH의 활성도는 9일 배양시 11.07이며 10일 배양시에는 12.12이였고, MDH는 각각 11.89와 13.44로 나타났다. 그리고 SDH는 9일 배양군에서는 8.45이며 10일 배양군에서는 10.52의 활성을 보여 증가했음을 알 수 있다. ATP의 변화는 10일 배양군$(2.10\times10^{-4}mol/ml)$이 9일 배양군$(2.50\times10^{-6}mol/ml)$에 비해 감소현상을 보였다.

• 약학회지
• /
• 제37권1호
• /
• pp.84-88
• /
• 1993

Brovincamine is a selective cerebral vasodilator that was apparently produced via a slow calcium blockade. Brovincamine has been shown to increase ATP production and glucose and oxygen consumption in brain, improving energy metabolism. Also brovincamine inhibited platelet aggregation induced by ADP and collagen in vivo and in vitro via an increase of cAMP concentration, promoting therapeutic effects on cerebral circulatory disorders. So we investigated and represented the clinical effects and safety of brovincamine in patients with cerebral stroke. Thirty patients of cerebral stroke that was older than 2 months, who were 22 cases of cerebral infarction, 6 of cerebral embolism that originated from carebral infarction, 6 of cerebral embolism that originated from cardiac diseases, and 2 of cerebral embolism that originated from cardiac diseases, and 2 of cerebral hemorrhage, were administered of 20 mg of oral brovincamine three times daily for 8 weeks. Improvement rates of each symptom after 8 week administration were 30.8% for subjective symptoms, 76% for psychiatric symptoms and 65.6% for neurologic symptoms. In final global improvement rates, much improvement was 10%, improvement was 23.3% slight improvement is 36.7%, and no change was 30%. So global improvement rate including slight improvement was 70%. As for side effects, there were 3 cases of mild gastrointestinal symptoms, but there were no other subjective side effects and significant fluctuation in laboratory examination. Conclusively throughout the present study, brovincamine is judged to be well tolerated and effective in patients with cerebral stroke.