• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.64-64
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• 2003

It is thought that highly reactive oxygen radicals generated at the ischemia-reperfusion in case of strokes play an important role in damaging the brain. We examined the neuroprotective effects from the several medicinal herbs in the transient ischemic rat model and compared their effects with the free radical scavenging activities. Transient ischemia was induced by intraluminal occusion of the right middle cerebral artety for 120 min and reperfusion was continued for 22 h in rats. The free radical scavenging properties of medicinal herbs were examined in vitro by determination of the interaction with the 1,l-diphenyl-2-picrylhydrazyl (DPPH) stable free radical. Aqueous extracts of 11 medicinal herbs (200 mg/kg) were orally administered, promptly prior to reperfusion and 2 h after reperfusion. Total infarction volume in the ipsilateral hemisphere of ischemia reperfusion rats was significantly lowered by the treatment of 7 medicinal herbs (Sophora flavescens, Lycopus lucidus, Sanguisorba officinalis, Caesalpinia sappan, Albizia julibrissin, Rubia akane, Psoralea corylifolia, Prunella vulgaris). However, all of these medicinal herbs did not show antioxidative activities. These results suggest that neuroprotective effects of several drugs are not always correlated with their antioxidative properties.

• Archives of Pharmacal Research
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• v.27 no.11
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• pp.1136-1140
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• 2004

Red ginseng and fermented red ginseng were prepared, and their composition of ginsenosides and antiischemic effect were investigated. When ginseng was steamed at 98-$100{\circ}C$ for 4h and dried for 5h at $60{\circ}C$, and extracted with alcohol, its main components were ginsenoside $Rg_3$ > ginsenoside $Rg_1$> ginsenoside $Rg_2$. When the ginseng was suspended in water and fermented for 5 days by previously cultured Bifidobacterium H-1 and freeze-dried (fermented red ginseng), its main components were compound K > ginsenoside $Rg_3{\geq}$ ginsenoside $Rg_2$. Orally administered red ginseng extract did not protect ischemia-reperfusion brain injury. However, fermented red ginseng significantly protected ischemica-reperfusion brain injury. These results suggest that ginsenoside Rh2 and compound K, which was found to be at a higher content in fermented red ginseng than red ginseng, may improve ischemic brain injury.

• Korean Journal of Pharmacognosy
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• v.34 no.4 s.135
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• pp.335-338
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• 2003

It is thought that highly reactive oxygen species generated after strokes plays a key role in damaging the brain. We examined free radical scavenging activity and neuroprotective effects of several medicinal herbs in a rat model of transient ischemia. Free radical scavenging property of medicinal herbs was examined in vitro using 1,1-diphenyl-2-picrylhydrazyl stable free radical. Transient ischemia was induced by intraluminal occlusion of the right middle cerebral artery for 120 min, followed by reperfusion for 22 hr in rats. Aqueous extracts of 8 medicinal herbs (200 mg/kg) were orally administered twice to transient ischemic rat prior to reperfusion and 2 hr after reperfusion. Total infarction volume in the hemisphere ipsilateral to the ischemia-reperfusion was significantly decreased in 7 groups treated with Sophora flavescens, Lycopus lucidus, Sanguisorba officinalis, Caesalpinia sappan, Albizia julibrissin, Rubia akane, Psoralea corylifolia, or Prunella vulgaris. However, neuroprotective effects of these medicinal herbs were not correlated with their antioxidative activities. These results suggest that these medicinal herbs exert neuroprotection via antioxidative as well as unknown mechanism.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.62-62
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• 2003

It is now convincing that free radical generation is involved in the pathophy siological mechanisms of ischemic stroke, particularly in ischemia-reperfusion injury. The present study, therefore, examined neuroprotective effect of aloesin isolated from Aloe vera, which was known to have antioxidative activity, in a rat model of transient focal cerebral ischemia. Transient focal cerebral ischemia was induced by occlusion of middle cerebral artery for 2 hr with a silicone-coated 4-0 nylon monofilament in male Sprague-Dawley rats under isoflurane anesthesia Aloesin (1, 3, 10, 30 and 50 mg/kg/injection) was administered intravenously 3 times at 0.5, 2 and 4 hr after onset of ischemia. Neurological score was measured 24 hr after onset of ischemia immediately before sacrifice. Seven serial coronal slices of the brain were stained with 2,3,5-triphenyltetrazolium chloride and infarct size was measured using a computerized image analyzer. Treatment with the close of 1 or 50 mg/kg did not significantly reduce infarct volume compared with the saline vehicle-treated control group. However, treatments with the closes of 3 and 10 mg/kg significantly reduced both infarct volume and edema by approximately 47% compared with the control group, producing remarkable behavioral recovery effect. Treatment with the close of 30 mg/kg also significantly reduced infarct volume to a lesser extent by approximately 33% compared with the control group, but produced similar degree of behavioral recovery effect. In addition, general pharmacological studies showed that aloesin was a quite safe compound. The results suggest that aloesin can serve as a lead chemical for the development of neuroprotective agents by providing neuroprotection against focal ischemic neuronal injury.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.305.1-305.1
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• 2002

The temporal profiles of the changes of dopaminergic cell and microglial activation induced by transient cerebral ischemia was investigated in the substantia nigral region which lay outside ischemic areas of rat brain after middle cerebral artery occlusion (MCAO). Transient cerebral ischemia was induced by intraluminal occlusion of the right middle cerebral artery for 2 hand reperfusion was continued for 1, 2. 3. 7. 10. 14. 30, 60. and 120 days. Activated microglial cells were visualized with immunohistochmistry using OX-43 antibody. (omitted)

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.6
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• pp.435-440
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• 2010

Valproic acid (VPA) is a well-known anti-epileptic and mood stabilizing drug. A growing number of reports demonstrate that VPA is neuroprotective against various insults. Despite intensive efforts to develop new therapeutics for stroke over the past two decades, all treatments have thus far failed to show clinical effect because of treatment-limiting side effects of the drugs. Therefore, a safety-validated drug like VPA would be an attractive candidate if it has neuroprotective effects against ischemic insults. The present study was undertaken to examine whether pre- and post-insult treatments with VPA protect against brain infarct and neurological deficits in mouse transient (tMCAO) and permanent middle cerebral artery occlusion (pMCAO) models. In the tMCAO (2 hr MCAO and 22 hr reperfusion) model, intraperitoneal injection of VPA (300 mg/kg, Lp.) 30 min prior to MCAO significantly reduced the infarct size and the neurological deficit. VPA treatment immediately after reperfusion significantly reduced the infarct size. The administration of VPA at 4 hr after reperfusion failed to reduce the infarct size and the neurological deficit. In the pM CAO model, treatment with VPA (300 mg/kg, i.p.) 30 min prior to MCAO significantly attenuated the infarct size, but did not affect the neurological deficit. Western blot analysis of acetylated H3 and H4 protein levels in extracts from the ischemic cortical area showed that treatment with VPA increased the expression of acetylated H3 and H4 at 2 hrs after MCAO. These results demonstrated that treatment with VPA prior to ischemia attenuated ischemic brain damage in both mice tMCAO and pMCAO models and treatment with VPA immediately after reperfusion reduced the infarct area in the tMCAO model. VPA could therefore be evaluated for clinical use in stroke patients.

• Reproductive and Developmental Biology
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• v.35 no.2
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• pp.167-174
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• 2011

Acute ischemic stroke results from sudden decrease or loss of blood supply to an area of the brain, resulting in a coinciding loss of neurological function. The antioxidant action of melatonin is an important mechanism among its known effects to protective activity during ischemic/reperfusion injury. The focus of this research, therapeutic efficacy of melatonin on recovery of neurological function following long term treatment in ischemic brain injured rats. Male Sprague-Dawley rats (n=40; 8 weeks old) were divided into the control group, and MCAo groups (Vehicle, MT7 : MCAo+ melatonin injection at 7:00, MT19 : MCAo+melatonin injection at 19:00, and MT7,19 : MCAo+melatonin injection at 7:00 and 19:00). Rat body weight and neurological function were measured every week for 8 weeks. After 8 weeks, the rats were anesthetized with a mixture of zoletil (40 mg/kg) and xylazine (10 mg/kg) and sacrificed for further analysis. Tissues were then collected for RNA isolation from brain tissue. Also, brain tissues were analyzed by histological procedures. We elucidated that melatonin was not toxic in vital organs. MT7,19 was the most rapidly got back to mild symptom on test of neurological parameter. Also, exogenous melatonin induces both the down-regulation of detrimental genes, such as NOSs and the up-regulation of beneficial gene, including BDNF during long term administration after focal cerebral ischemia. Melatonin treatment reduced the loss of primary motor cortex. Therefore, we suggest that melatonin could be act as prophylactic as well as therapeutic agent for neurorehabilitative intervention.

• The Korea Journal of Herbology
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• v.21 no.2
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• pp.151-158
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• 2006

Objectives : The purpose of the present study is to observe the neuroprotective effect of the $NeuBo153^{\circledR}$ on transient focal cerebral ischemia in rats. Methods : $NeuBo153^{\circledR}$ was made by mixing the herbs, mainly the root of Panax ginseng, the root of Rehmannia glutinosa and Poria cocos, the stem bark of Acanthopanax senticosus, the root of Scutellaria baicalensis and Mel, and heating for 96 hours. Transient Focal cerebral ischemia (2 h of ischemia, 22 h of reperfusion) was induced by intraluminal suture method with SD rats. Sensory motor function was tested by rotarod test, prehensile traction test, beam balance test and foot fault test at 24 h after ischemia. The brain slices were stained by 2% 2, 3, 5-triphenyltetrazolium chloride and the infarct volume was measured by graphic analyzer at 24 h after ischemia. Results : $NeuBo153^{\circledR}$ treated group did not show significant differences compared with vehicle treated group in body temperature. Oral administration of $NeuBo153^{\circledR}$ reduced brain infarct volume by 29.7% compared with vehicle treated group. $NeuBo153^{\circledR}$ also showed protective effects on sensory motor functional deficits. Conclusion : $NeuBo153^{\circledR}$ treatment reduced brain damage and improved functional deficits induced by MCAo. It showed neuroprotective effects even when treatment was relayed 2 h after injury. Further research is required to evaluating long term functional recovery am accurate therapeutic range and mechanisms.

• Biomolecules & Therapeutics
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• v.8 no.2
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• pp.160-166
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• 2000

The present study examined influence of various ischemic duration on extent of focal ischemic brain injury induced by middle cerebral artery occlusion (MCAO) in rats. The MCAO was produced by insertion of a 17 mm silicone-coated 4-0 nylon surgical thread to the origin of MCA through the internal carotid artery for 30, 60, 90, 120 min (transient) or 24 hr (permanent) in male Sprague-Dawley rats under isoflurane anesthesia. Reperfusion in transient MCAO models was achieved by pulling the thread out of the internal carotid artery. Only rats showing neurological deficits characterized by left hemiparesis and/or circling to the left, were included in cerebral ischemic groups. The rats were sacrificed 24 hr after MCAO and seven serial coronal slices of the brain were stained with 2,3,5-triphenyltetrazolium chloride. Infarct size was measured using a computerized image analyzer. Ischemic damage was common in the frontoparietal cortex (somatosensory area) and the lateral segment of the striatum while damage to the medial segment of the striatum depended on the duration of the occlusion. In the 30-min MCAO grouts, however, infarcted region was primarily confined to the striatum and it was difficult to clearly delineate the region since there was mixed population of live and dead cells in the nucleus. Infarct volume was generally increased depending on the duration of MCAO, showing the most severe damage in the permanent MCAO group. However, there was no significant difference in infarct size between the 90-min and 120-min MCAO groups. % Edema also tended to increase depending on the duration of MCAO. The results suggest that the various focal ischemic rat models established in the present study can be used to evaluate in vivo neuroprotective activities of candidate compounds or to elucidate pathophysiological mechanisms of ischemic neuronal cell death.

• The Korea Journal of Herbology
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• v.23 no.2
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• pp.225-233
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• 2008

Objectives : The purpose of the present study was to development of neuroprotective antioxidant agents. For the purpose, we investigated the neuroprotective effect of anti oxidant herb, the root of Polygonum cuspidatum on transient focal cerebral ischemia in rats. Methods : The roots of Polygonum cuspidatum were extracted by 85% MeOH (PCE). Radical scavenging effects were investigated using DPPH assay and TBARs (Thiobarbituric acid reaction substance) assay in brian homogenates. Neuroprotective effect was investigated using transient focal cerebral ischemia rat model (2 h of ischemia, 22 h of reperfusion) by behavioral test and measurement of brain damage using 2, 3, 5-triphenyltetrazolium chloride staining. Results : PCE showed potent and dose dependent radical scavenging effects in DPPH and TBARs assay. Oral administration of PCE reduced brain infarct volume by 29.7% and improved the sensory motor functional deficit by 29% compared with vehicle treated group. Conclusions : PCE showed radical scavenging effects and neuroprotective effect on stroke rat model. Therefore, Polygonum cuspidatum could be a candidate for the development of neuroprotective-antioxidant agents.