• Biomolecules & Therapeutics
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• v.17 no.3
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• pp.270-275
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• 2009

Polyethylene glycol-conjugated hemoglobin (PEG-Hb) has been proposed as a blood substitute for transfusion due to their plasma expansion and oxygen transport capabilities. The protective effect of PEG-Hb on cerebral hypoxic-ischemic injury was investigated in neonatal hypoxia model and adult rat focal cerebral ischemia model. As intravenously administered 30 min before the onset of hypoxia, PEG-Hb markedly protected cerebral hypoxic injury in a neonatal rat hypoxia model. A similar treatment of PEG-Hb largely reduced the ischemic injury ensuing after 2-h middle cerebral artery occlusion followed by 22-h reperfusion. Consistently, neurological disorder was significantly improved by PEG-Hb. The results indicate that the pharmacological blockade of cerebral ischemic injury by using PEG-Hb may provide a useful strategy for the treatment of cerebral stroke.

• Journal of Acupuncture Research
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• v.33 no.3
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• pp.101-116
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• 2016

Objectives : This research was performed to investigate the effects of Ukgansan pharmacopuncture(U-PA) of focal brain ischemia induced by middle cerebral artery occlusion(MCAO) in rats. Methods : The subjects were divided into 5 groups : A control group, acupuncture group, pharmacopuncture group U-PA1($2.571mg/250g/40{\mu}{\ell}$), pharmacopuncture group U-PA2($6.428mg/250g/40{\mu}{\ell}$), and pharmacopuncture group U-PA3($12.855mg/250g/40{\mu}{\ell}$). The focal brain ischemia was induced by intraluminal filament insertion into the middle cerebral artery. After 3 days of MCAO, Ukgansan(UGS) pharmacopuncture treatment was performed on the GB20, and the day after being treated with pharmacopuncture, the Morris water maze test was carried out by the assigned group. The series of processes were treated 6 times. Thereafter Bax, Bcl-2, Bax/Bcl-2 ratio, mGluR5, density of neuronal cell, and ChAT were measured. Results : The results were as follows. 1. The intensity of Bax significantly decreased in the U-PA1, U-PA2, U-PA3 groups. 2. The Bax/Bcl-2 ratio significantly decreased in the U-PA3 group compared with the control group. 3. The neuroprotective effect on the hippocampal CA1 significantly increased in the U-PA1, U-PA2, U-PA3 groups compared with the control group. 4. The density of ChAT in the hippocampal CA1 significantly increased in the U-PA1, U-PA2, U-PA3 groups compared with the control group. Conclusion : These results suggest that UGS pharmacopuncture may have anti-apoptotic and neuroprotective effects on focal cerebral ischemia caused by intraluminal filament insertion into the middle cerebral artery in rats.

• 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.

• 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 Pain
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• v.21 no.2
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• pp.119-125
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• 2008

Background: Cerebral blood vessels are innervated by sympathetic nerves from the superior cervical ganglia (SCG), and these nerves may influence the cerebral blood flow. The purpose of the present study was to evaluate the neuroprotective effect of superior cervical sympathetic ganglion block in rats that were subjected to focal cerebral ischemia/reperfusion injury. Methods: Eighty male Sprague-Dawley rats (270-320 g) were randomly assigned to one of two groups (the ropivacaine group and a control group). In all the animals, brain injury was induced by middle cerebral artery (MCA) reperfusion that followed MCA occlusion for 2 hours. The animals of the ropivacaine group received $30{\mu}l$ of 0.75% ropivacaine, and their SCG. Neurologic score was assessed at 1, 3, 7 and 14 days after brain injury. Brain tissue samples were then collected. The infarct ratio was measured by 2.3.5-triphenyltetrazolium chloride staining. The terminal deoxynucleotidyl transferase mediated dUTP-biotin nick-end labeled (TUNEL) reactive cells and the cells showing caspase-3 activity were counted as markers of apoptosis at the caudoputamen and frontoparietal cortex. Results: The death rate, the neurologic score and the infarction ratio were significantly less in the ropivacaine group 24 hr after ischemia/reperfusion injury. The number of TUNEL positive cells in the ropivacaine group was significantly lower than those values of the control group in the frontoparietal cortex at 3 days after injury, but the caspase-3 activity was higher in the ropivacaine group than that in the control group at 1 day after injury. Conclusions: The study data indicated that a superior cervical sympathetic ganglion block may reduce the neuronal injury caused by focal cerebral ischemia/reperfusion, but it may not prevent the delayed damage.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.3
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• pp.257-263
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• 2009

This study aimed to investigate whether selective serotonin reuptake inhibitors (SSRIs) attenuate brain injury and facilitate recovery following photothrombotic cortical ischemia in mice. Male ICR mice were anesthetized and systemically administered Rose Bengal. Permanent focal ischemia was induced in the medial frontal and somatosensory cortices by irradiating the skull with cold light laser. The animals were treated with fluoxetine or sertraline once a day for 14 d starting 1 h after ischemic insult. Treatment with fluoxetine and sertraline significantly reduced the infarct size. The Evans blue extravasation indices of the fluoxetine- and sertraline-treated groups were significantly lower than that of the vehicle group. Treatment with fluoxetine and sertraline shifted the lower limit of the mean arterial blood pressure for cerebral blood flow autoregulation toward normal, and significantly increased the expression of heme oxygenase-1 (HO-1) and hypoxia-inducible factor-1 ${\alpha}$ (HIF-1 ${\alpha}$) proteins in the ischemic region. These results suggest that SSRIs, such as fluoxetine and sertraline, facilitate recovery following photothrombotic cortical ischemia via enhancement of HO-1 and HIF-1 ${\alpha}$ proteins expression, thereby providing a benefit in therapy of cerebral ischemia.

• The Korean Journal of Physiology and Pharmacology
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• v.11 no.3
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• pp.85-88
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• 2007

Matrix metalloproteinases (MMPs) can degrade a wide range of extracellular matrix components. It has been reported that MMP-9 are activated after focal ischemia in experimental animals. (-)-Epigallocatechin-3-gallate (EGCG), a major constituent of green tea polyphenols, is a potent free radical scavenger and reduces the neuronal damage caused by oxygen free radicals. And it has been known that EGCG could reduce the infarction volume in focal brain ischemia and inhibit MMP-9 activity. To delineate the relationship between the anti-ischemic action and the MMP-9-inhibiting action of EGCG, we investigated the effect of EGCG on brain infarction and the activity of matrix metalloproteinase-9 induced by permanent middle cerebral artery occlusion (pMCAO) in ICR mice. EGCG (40 mg/kg, i.p. $15{\sim}30min$ prior to MCAO) significantly decreased infarction volume at 24 hr after MCAO. GM 6001 (50 mg/kg, i.p. $15{\sim}30min$ prior to MCAO), a MMP inhibitor, also significantly reduced infarction volume. In zymogram, MMP-9 activities began to increase at ipsilateral cortex at 2 hr after MCAO, and the increments of MMP-9 activities were attenuated by EGCG treatment. Western blot for MMP-9 also showed patterns similar to that of zymogram. These findings demonstrate that the anti-ischemic action of EGCG ire mouse focal cerebral ischemia involves its inhibitory effect on MMP-9.

• The Journal of Korean Medicine
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• v.23 no.1
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• pp.1-10
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• 2002

Objectives: Uncariae Ramulus Et Uncus extract is clinically used in Korea to treat ischemic cerebral damage. The present study was undertaken to study the neuroprotective effect of Uncariae Ramulus Et Uncus extract in middle cerebral artery occlusion (MCAO) rats. Methods: Changes of extracellular levels of dopamine, DOPAC, HVA. and HIAA in striatum were collected at 20 minutes interval by in vivo microdialysis and then analyzed by HPLC (high performance liquid chromatography) in rats subjected to permanent focal cerebral ischemia induced by 2 hours of MCAO. Uncariae Ramulus Et Uncus extract was orally administrated before MCAO. Different animals were used for measurement of cerebral infarction volume induced by 24 hours of MCAO with TIC staining and image analysis. Results: Extracellular levels of dopamine decreased after treatment with Uncariae Ramulus Et Uncus extract, while extracellular levels of DOPAC and HVA significantly increased. Cerebral infarction volume also significantly decreased after treatment with Uncariae Ramulus Et Uncus extract. Conclusions: These results provided evidence that Uncariae Ramulus Et Uncus extract can produce a neuroprotective effect on cerebral ischemia by regulating extracellular excitatory neurotransmitters.

• 대한핵의학회:학술대회논문집
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• 1992.06a
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• pp.183.1-183.1
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• 1992

• The Korean Journal of Pain
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• v.20 no.2
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• pp.83-91
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• 2007

Background: Cerebral blood vessels are innervated by sympathetic nerves that originate in the superior cervical ganglia (SCG). This study was conducted to determine the effect of an SCG block on brain injury caused by focal cerebral ischemia/reperfusion in a rat model. Methods: Male Sprague-Dawley rats (270-320 g) were randomly assigned to one of three groups (lidocaine, ropivacaine, and control). After brain injury induced by middle cerebral artery (MCA) occlusion/reperfusion, the animals were administered an SCG bloc that consisted of $30{\mu}l$ of 2% lidocaine or 0.75% ropivacaine, with the exception of animals in the control group, which received no treatment. Twenty four hours after brain injury was induced, neurologic scores were assessed and brain samples were collected. The infarct and edema ratios were measured, and DNA fragmented cells were counted in the frontoparietal cortex and the caudoputamen. Results: No significant differences in neurologic scores or edema ratios were observed among the three groups. However, the infarct ratio was significantly lower in the ropivacaine group than in the control group (P < 0.05), and the number of necrotic cells in the caudoputamen of the ropivacaine group was significantly lower than in the control group (P < 0.01). Additionally, the number of necrotic and apoptotic cells in theropivacaine group were significantly lower than inthe control group in both the caudoputamen and the frontoparietal cortex (P < 0.05). Conclusions: Brain injury induced by focal cerebral ischemia/reperfusion was reduced by an SCG block using local anesthetics. This finding suggests that a cervical sympathetic block could be considered as another treatment option for the treatment of cerebral vascular diseases.