• Biomolecules & Therapeutics
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• v.13 no.1
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• pp.35-40
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• 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.

• YAKHAK HOEJI
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• v.33 no.3
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• pp.149-155
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• 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.

• YAKHAK HOEJI
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• v.36 no.3
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• pp.278-284
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• 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
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• v.5 no.3
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• pp.306-315
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• 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
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• v.29 no.6
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• pp.719-724
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• 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
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• v.5 no.4
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• pp.402-411
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• 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
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• v.7 no.1
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• pp.79-88
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• 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.

• YAKHAK HOEJI
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• v.38 no.1
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• pp.57-66
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• 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
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• v.29 no.4
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• pp.459-470
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• 1999

To investigate the changes during the differentiation of the cerebral neurons of the embryogenic day (ED) 9 and 10, investigated the ultrastructural changes in the cerebral neurons by Electromicroscope, also cerebral protein, the activity of dehydronases (LDH, MDH and SDH) and changes of adenosine triphosphate concentration were analyzed, the result obtained are as follows. In the ultrastructural changes in the cerebral neurons, chromatin in 9 day-old chick embryos are comparatively distributed to even in neucleoplasm and could investigate very prominently that nuclear membrane is double-layer. Esperially, Rough endoplasmic reticulum (RER) and Golgi complex are developed well, also polysome is investigated and synaptic vesicles were scattered. In 10 day-old chick embryos, chromatin evenly spread and nuclear membrane could be differentiated prominently. Rough endoplasmic reticulum (RER) contain cytoplasm, mitochondria and Golgi complex are comparatively developed well. In 9 day-old cultural group of chick embryo cerebrum were separated 37 polypeptide bands and In 10 day-old cultural group of chick embryo cerebrum were separated 38 poly -peptide bands. The more culture time increase, the more the activity of dehydronases (LDH, MDH and SDH) increase. LDH activity was 11.07 (9th day) and 12.12 (10th day), MDH activity was 11.89 (9th day) and 13.44 (10th day) and SDH activity was 8.45 (9th day) and 10.52 (10th day) respectively. The ATP concentration degreesed 10 day-old cultural group than 9 day-old cultural group.

• YAKHAK HOEJI
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• v.37 no.1
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• pp.84-88
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• 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.