• Korean Journal of Acupuncture
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• v.23 no.3
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• pp.81-98
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• 2006

Objectives : Acupuncture using a tonification or sedation techniques method is used as a controlling the medication for an early stroke in the Korean medicine. LR3 has indicatons of headache, vertigo, facial paralysis, apoplexy, epiepsy as the source acupoint of a liver meridian. So this study is aims to investigate the anti-apoptotic and neuroprotective effects of acupuncture on the focal ischemia induced by intraluminal filament insertion in rats. Methods : The focal ischemia was induced by intraluminal filament insertion into middle cerebral artery. The animals were divided into seven groups (n=8 in each group) : Normal, intactness group; Conrol group, no therapy group after being ischemia induced; MA-l, acupuncture perpendicularly without Tonification or Sedation techniques at LR3 after being ischemia induced; MA-2, acupuncture obliquely towards the knee at LR3 after being ischemia induced; MA-3, acupuncture obliquely towards the toe at LR3 after being ischemia induced; MA-4, acupuncture obliquely towards the knee and rotate 9 times in a clockwise direction at LR3 after being ischemia induced; MA-5, acupuncture obliquely towards the toe and rotate 6 times in a counterclockwise direction at LR3 after being ischemia induced. The anti-apoptotic and neuroprotective effects of Acupuncture techniques of tonification or sedation at LR3 are observed by mGluR5, Bax, Cresyl violet, ChAT-stain and NGF. Results : The intensity of mGluR5 and the density of ChAT was increased in MA-1 group. The intensity of Bax was decreased in MA-3, MA-4 group. The density of neurons stained by Cresyl violet and ChAT was increased in MA-2, MA-3, MA-4, MA-5 group. The density of neurons stained by NGF was only increased in MA-4 group. Conclusions : Our study suggests that acupuncture perpendicularly without Tonification or Sedation techniques and obliquely towards the knee and rotate 9 times in a clockwise direction(Tonifying technique) at LR3 after being ischemia induced at LR3 shows anti-apoptotic and neuroprotective effects on cholinergic neuron in focal cerebral ischemia of the stroke in rats.

• The Journal of Korean Medicine
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• v.30 no.3
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• pp.70-78
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• 2009

Objectives : This study was aimed at examining the effects of the application of EA (electroacupuncture) at GV20 and LI4 in the early cerebral ischemia on the size of cerebral infarction, COX-2 and IL-6. Methods : For this experiment, 21, six-week-old male S-D (Sprague - Dawley) rats weighting 160g to 200g were selected and randomly classified into 3 groups, seven rats in each group. Brain ischemia was simulated using a modified Koizumi method which was performed on each rat. In the GV20 group, the GV20 of the SD rats was stimulated for thirty minutes with acupunctural electrode low frequency stimulator five hours after inducement of ischemia. For the LI4 group, the LI4 was stimulated as above, while for the Ischemia group, no stimulation was applied. Twenty-four hours after the experiment, stained cerebral tissues were examined and an immuno-histological test was done to examine inflammatory reaction Results : Out of the three groups, the LI4 group showed the smallest size of cerebral infarction and the Ischemia group showed the highest COX-2 (cyclooxygenase-2) expression value in the cortex of the cerebrum. In addition, the LI4 group showed the lowest COX-2 expression value in unknown putamen out of the three groups. Conclusions : We infer that EA, applied at LI4 and GV20 in early ischemia, is effective in delaying the expression of IL-6 (interleukin-6) and COX-2, the inflammatory agents manifested from stroke. In addition, application at LI4, rather than GV20, can lower the expression value of the inflammatory agents. Further, EA can be an effective way to block early inflammatory reaction in stroke.

• Journal of Korean Neurosurgical Society
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• v.49 no.1
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• pp.1-7
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• 2011

Objective: Glutamate is a key excitatory neurotransmitter in the brain, and its excessive release plays a key role in the development of neuronal injury. In order to define the effect of nimodipine on glutamate release, we monitored extracellular glutamate release in real-time in a global ischemia rat model with eleven vessel occlusion. Methods: Twelve rats were randomly divided into two groups: the ischemia group and the nimodipine treatment group. The changes of extracellular glutamate level were measured using microdialysis amperometric biosensor, in coincident with cerebral blood flow (CBF) and electroencephalogram. Nimodipine (0.025 ${\mu}g$/100 gm/min) was infused into lateral to the CBF probe, during the ischemic period. Also, we performed Nissl staining method to assess the neuroprotective effect of nimodipine. Results: During the ischemic period, the mean maximum change in glutamate concentration was $133.22{\pm}2.57\;{\mu}M$ in the ischemia group and $75.42{\pm}4.22\;{\mu}M$ (p<0.001) in the group treated with nimodipine. The total amount of glutamate released was significantly different (P<0.001) between groups during the ischemic period. The %cell viability in hippocampus was $47.50{\pm}5.64$ (p<0.005) in ischemia group, compared with sham group. But, the %cell viability in nimodipine treatment group was $95.46{\pm}6.60$ in hippocampus (p<0.005). Conclusion: From the real-time monitoring and Nissl staining results, we suggest that the nimodipine treatment is responsible for the protection of the neuronal cell death through the suppression of extracellular glutamate release in the 11-VO global ischemia model of rat.

• Biomolecules & Therapeutics
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• v.25 no.4
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• pp.383-389
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• 2017

Dexmedetomidine is an ${\alpha}2$-adrenergic receptor agonist that exhibits a protective effect on ischemia-reperfusion injury of the heart, kidney, and other organs. In the present study, we examined the neuroprotective action and potential mechanisms of dexmedetomidine against ischemia-reperfusion induced cerebral injury. Transient focal cerebral ischemia-reperfusion injury was induced in Sprague-Dawley rats by middle cerebral artery occlusion. After the ischemic insult, animals then received intravenous dexmedetomidine of $1{\mu}g/kg$ load dose, followed by $0.05{\mu}g/kg/min$ infusion for 2 h. After 24 h of reperfusion, neurological function, brain edema, and the morphology of the hippocampal CA1 region were evaluated. The levels and mRNA expressions of interleukin-$1{\beta}$, interleukin-6 and tumor nevrosis factor-${\alpha}$ as well as the protein expression of inducible nitric oxide synthase, cyclooxygenase-2, nuclear factor-${\kappa}Bp65$, inhibitor of ${\kappa}B{\alpha}$ and phosphorylated of ${\kappa}B{\alpha}$ in hippocampus were assessed. We found that dexmedetomidine reduced focal cerebral ischemia-reperfusion injury in rats by inhibiting the expression and release of inflammatory cytokines and mediators. Inhibition of the nuclear factor-${\kappa}B$ pathway may be a mechanism underlying the neuroprotective action of dexmedetomidine against focal cerebral I/R injury.

• Korean Journal of Medicinal Crop Science
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• v.22 no.1
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• pp.46-52
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• 2014

In traditional Korean and Chinese medicine, safflower (Carthamus tinctorius L.) for the treatment of central nervous system-related symptoms such as tremor, seizure, stroke and epilepsy. We investigated the effects of safflower could influence cerebral ischemia-induced neuronal and cognitive impairments. Administration of safflower for 1 day (200 mg/kg body weight, p.o.) increased the survival of hippocampal CA1 pyramidal neurons after transient global brain ischemia. And neurological functions measured as short term memory. Post-treatment with safflower for 2 times decreased the induction/reduction - induced production of neuronal cell loss from global cerebral ischemia. Safflower markedly decreased neuronal cell death and also caused a decrease in the content of thiobarbituric acid-reacting substances (TBARS) ($55.2{\pm}9.4{\mu}mol\;mg^{-1}$) and significant improvement of activities of glutathione (GSH) ($27.2{\pm}5.0{\mu}mol\;mg^{-1}$) in hippocampus. We conclude that treatment with safflower attenuated learning and memory deficits, and neuronal cell loss induced by global cerebral ischemia. These results suggest that safflower may be a potential candidate for the treatment of vascular dementia.

• The Korean Journal of Pharmacology
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• v.29 no.1
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• pp.1-8
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• 1993

To elucidate involvement of platelet-activating factor (PAF) in cerebral ischemia-reperfusion injury, male Sprague-Dawley rats and albino mice of either sex were subjected to a 10-min bilateral carotid artery occlusion and 6-hr recirculation. The McGraw stroke index in mice was markedly inhibited by PAF antagonists, BN 52021 and CV 6209 (1 mg/kg, i.p., each) When they were administered 10 min before bilateral carotid artery occlusion or 1 hr after reperfusion. The increases in brain water content were significantly attenuated by treatment with BN 52021 or CV 6209 in both animals. BN 52021 exhibited a significant improvement in the postischemic blood pressure change in association with a beneficial effect on the delayed dilatation of pial arterioles after 10 min of ischemia. Thus it is suggested that PAF plays an important role as an endogenous mediator in development of cerebral ischemia-reperfusion injury, and further, specific antagonists to PAF will be able to prevent or reverse the pathological sequelae of cerebral ischemia.

• 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.

• Clinical and Experimental Pediatrics
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• v.51 no.8
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• pp.874-878
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• 2008

Purpose : This study was undertaken to develop an animal model of periventricular leukomalacia (PVL) induced by in utero clamping of pregnant rat aorta in fetal rats. Methods : A timed pregnanct Sprague-Dawley rat on embryonic day 21 just prior to delivery was sedated and anesthetized, and a Harvard ventilator for small animals was applied. Following laparotomy, the maternal aorta was clamped reversibly for 40 minutes using a surgical clip. The fetal rats were then delivered by Cesarean section, resuscitated if necessary, and reared by a surrogate mother rat until postnatal day 21 to obtain the brain specimen. After systemic perfusion and fixation, $10{\mu}m$ thick serial brain sections were obtained and stained for pathologic examination and assessment of ventriculomegaly. Ventriculomegaly was assessed by the measured ventricle to total brain volume ratio. Results : Eight out of eleven fetal rats (73%) survived in the ischemia group after induction of in utero ischemia by clamping maternal rat aorta, and all ten survived in the control group. Body and brain weights measured at postnatal day 21 were significantly lower in the ischemia group compared to the control group. In pathologic findings, significant ventriculomagaly ($3.67{\pm}1.21%$ vs. $0.23{\pm}0.06%$) was observed in the ischemia group compared to the control group; although cystic lesion was not observed, mild (n=6) and moderate (n=2) rerefaction of the brain tissue was observed. Conclusion : A fetal rat model of PVL induced by in utero clamping of pregnant rat aorta was developed.

• 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.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.3
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• pp.760-764
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• 2005

This research was performed to investigate protective effect of Sophora Subprostrata fractions against focal ischemic brain damage after middle cerebral artery(MCA) occlusion. Rats were divided into six groups: MCA-occluded group(Control); each administered groups with Sophora Subprostrata total phase(Total), Sophora Subprostrata Aqueous phase (Aqueous), Sophora Subprostrata BuOH phase(BuOH), and Sophora Subprostrata Alkaloid phase(Alkaloid) after MCA-occlusion; sham-operated group(Sham). The right MCA was occluded by A poly-L-lysine coated 4-0 nylon suture thread through the internal carotid artery permanently. Sophora Subprostrata and fractions were administered orally(5mg/ml) for 7 days after MCA-occlusion. The behavior of ischemic rats were examined at 24 hours, 3, 5 and 7 days after MCA-occlusion from the views of 4 different aspects: posture & balance tests(4 subtests), reflex tests(6 subtests), muscle-tone tests(3 subtests), and foot-fault test. The results showed that 1) in muscle tone test, Sophora Subprostrata total phase only increased reduced muscle tone function from 3 to 7 days, 2) in reflex test, Sophora Subprostrata total and Aqueous phase increased fast recovery from 24 hours and 3 days, 3) in posture & balance test, Sophora Subprostrata total and Aqueous phase increased fast recovery from 24 hours, and Sophora Subprostrata BuOH and Alkaloid phase increased posture & balance function from 3 days, but 4) in motor function test, Sophora Subprostrata did not show effective recovery compared with control group. In conclusion, Sophora Subprostrata has protective effects against brain damage at the early stage of focal cerebral ischemia. Sophora Subprostrata total and Aqueous phase produced more pronounced protective effect against focal ischemic brain damage.