• 동의생리병리학회지
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• 제18권4호
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• pp.1083-1088
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• 2004

This Study was designed to investigate the mechanism of Prescription for Treatment Abundant Expectoration due to Deficiency of Qi(Yukgunja-Tang, YGT) on cerebral hemodynamics [regional cerebral blood f1ow(rCBF) and pial arterial diameter(PAD)] in cerebral ischemia rats. The results were as follows: Both rCBF and PAD were significantly and stably decreased by YGT (10㎎/㎏, i.p.) during the period of cerebral reperfusion, which contrasted with the findings of rapid and marked increase in Control group. Pretreatment with indomethacin(1㎎/㎏, i.p.), an inhibitor of cyclooxygenase and methylene blue(10㎍/㎏, i.p.), an inhibitor of guanylate cyclase significantly but unstably increased the YGT-induced increases in rCBF during the period of cerebral reperfusion. Pretreatment with indomethacin significantly and stably decreased the YGT-induced increases in PAD during the period of cerebral reperfusion, but pretreatment with methylene blue increased unstably the YGT-induced increases in PAD during the period of cerebral reperfusion. In conclusion, the present authors thought that mechanism of YGT on cerebral hemodynamics was connected with guanylate cyclase in cerebral ischemia rats.

• Archives of Pharmacal Research
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• 제23권4호
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• pp.413-417
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• 2000

The effect of ischemia/reperfusion-induced neuronal damage on the memory impairment were investigated using active avoidance and Morris water maze tasks in Wistar rats. Focal ischemia was induced by 1 h occlusion of the right middle cerebral artery (MCA) of Wistar male rats. Reperfusion was induced by releasing the occlusion and restoring the blood circulation for 24 h. The acquisition and preservation memory tested by active avoidance showed a significant difference between the sham and ischemia/reperfusion group. The water maze acquisition performance was also significant difference between sham and ischemia/repefusion groups in both latency and moving distance. The infarction volume was increased by the ischemia/reperfusion. Furthermore, the cresyl violet staining of the ischemia/reperfusion brain showed severe neuronal damage (pyramidal cell loss) in the cortex in addition to the striatum lesion of brain. This study shows that pyramidal cell damage in the cortex lesion may be partially related to memorial disturbance in the ischemia/reperfusion brain injury.

• 동의생리병리학회지
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• 제18권5호
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• pp.1404-1409
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• 2004

Cheonmabanhwa-Tang(CBT) has been used in the Oriental Medicine for many centuries as a therapeutic agent for dizziness due to Poong-Dam. This Study was designed to investigate the mechanism of Prescription on cerebral hemodynamics [regional cerebral blood flow(rCBF) and pial arterial diameter(PAD)J in cerebral ischemia rats, The results in cerebral ischemic rats were as follows: Both rCBF and PAD were significantly and stably increased by CBT (10 ㎎/㎏, i.p.) during the period of cerebral reperfusion, which contrasted with the findings of rapid and marked increase in control group. Pretreatment with indomethacin(1 ㎎/㎏, i.p.), an inhibitor of cyclooxygenase significantly but unstably increased the CBT-induced increases in PAD as well as rCBF during the period of cerebral reperfusion. Pretreatment with methylene blue(10 (.1.㎍/㎏, i.p.), an inhibitor of guanylate cyclase significantly but unstably increased the CBT-induced increases in PAD as well as rCBF during 150 minutes of cerebral reperfusion, but decreased stably the CBT-induced increases in rCBF and PAD after 180 minutes of cerebral reperfusion. In conclusion, the present authors thought that CBT caused effect on cerebral hemodynamics via mediation of cyclooxygenase.

• 대한본초학회지
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• 제20권3호
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• pp.75-81
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• 2005

Objectives : In brain disorders such as ischemic stroke, the final outcome depends largely on the duration and the degree of the ischemia as well as the susceptibility of various cell types in the affected brain region. In the present study, the effects of Nodus Nelumbinis Rhizomatis Extract(NNRe) were tested for the anti-oxidative action of rCBF. Methods : Regional cerebral blood flow(rCBF) were determined by LDF methods. LDF allows for real time, noninvasive, continuous recordings of local CBF. The LDF method has been widely used to trace hemodynamic changes in the superficial or the deep brain structures in experimental stroke research. Results : NNRe treatment showed no change on rCBF in methylene blue, ODQ and L-NNA pretreated rats. 120 minutes of MCAO and followed reperfusion, 0.1% concentration of NNR treatment improved the altered cerebral hemodynamics of cerebral ischemic by increasing rCBF. Conclusions : The ischemia/reperfusion induced oxidative stress may have contributed to cerebral damage in rats, and the present study provides clear evidences for the beneficial effect of NNR on ischemia/reperfusion induced brain injury.

• Biomolecules & Therapeutics
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• 제7권3호
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• pp.234-241
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• 1999

The present study assessed the cerebroprotective effect of platelet-activating factor(PAF) antagonists in transient cerebral ischemia of rats. Right middle cerebral artery (MCA) of Sprague-Dawley rats was occluded for 2 hours using an intraluminal filament technique, and was reperfused for 6 hours following cerebral ischemia. The infarct area of seven coronal brain slices was measured morphometrically following stain ing in the 2% 2,3,5-triphenyltetrazolium chloride solution. The changes in regional cerebral blood flow (rCBF) and pial arteriolar diameter were measured by laser-Doppler flowmetry and by a videomicroscopy, respectively. The infarct size was significantly reduced by PAF antagonists, BN 52021 and CV-6209, which were administered i.p. 10 min before MCA occlusion. Pretreatment with PAF antagonists significantly restored the changes in pial arterial diameter as well as those in rCBF during the period of cerebral ischemia-reperfusion. PAF antagonists significantly inhibited the inducible nitric oxide synthase activity in the pial arteries ipsilateral to ischemia. These results suggest that PAF antagonists exert a cerebroprotective effect against ischemic brain damage through an improvement of postocclusive cerebral blood flow.

• The Korean Journal of Pain
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• 제21권2호
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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.

• Biomolecules & Therapeutics
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• 제25권3호
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• pp.272-278
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• 2017

Fucoidan has been reported to exhibit various beneficial activities ranging from to antivirus and anticancer properties. However, little information is available about the effects of fucoidan on cerebral ischemia-reperfusion injury (IRI). Our study aimed to explore the effects of fucoidan on cerebral IRI, as well as the underlying mechanisms. Sprague-Dawley (SD) rats were randomly subjected to four groups: Sham, IRI+saline (IRI+S), IRI+80 mg/kg fucoidan (IRI+F80), and IRI+160 mg/kg fucoidan (IRI+F160). Fucoidan (80 mg/kg or 160 mg/kg) was intraperitoneally injected from 7 days before the rats were induced to cerebral IRI model with middle cerebral artery occlusion (MCAO) method. At 24 h after reperfusion, neurological deficits and the total infarct volume were determined. The levels of inflammation-associated cytokines (interleukin (IL)-$1{\beta}$, IL-6, myeloperoxidase (MPO), and tumor necrosis factor (TNF)-${\alpha}$), oxidative stress-related proteins (malondialdehyde (MDA) and superoxide dismutase (SOD)) in the ischemic brain were measured by enzyme-linked immunosorbent assay (ELISA). Besides, the levels of apoptosis-related proteins (p-53, Bax, and B-cell lymphoma (Bcl)-2) and mitogen-activated protein kinase (MAPK) pathway (phosphorylation-extracellular signal-regulated kinase (p-ERK), p-c-Jun N-terminal kinase (JNK), and p-p38) were measured. Results showed that administration of fucoidan significantly reduced the neurological deficits and infarct volume compared to the IRI+S group in a dose-dependent manner. Also, fucoidan statistically decreased the levels of inflammation-associated cytokines, and oxidative stress-related proteins, inhibited apoptosis, and suppressed the MAPK pathway. So, Fucoidan plays a protective role in cerebral IRI might be by inhibition of MAPK pathway.

• 한방재활의학과학회지
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• 제20권3호
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• pp.1-11
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• 2010

Objectives : This study was designed to investigate the effects of Lumbricus extract(LE) on the regional cerebral blood flow(rCBF) in ischemic rats, further to determine the mechanism of action of LE, and the effects that LE inhibits lactate dehydrogenase(LDH) activity in brain cells. Methods and materials : This study, ischemic rats were divided into total four group: control group(n=6), experimental group I (LE treated group)(n=6), experimental group II(LE treated group after pretreatment with indomethacin)(n=6), experimental group III(LE treated group after pretreatment with methylene blue)(n=6). And the measurement that LE inhibits LDH activity in the damage to brain cells to N-methyl-D-aspartic acid(NMDA). The changes of rCBF were determinated by laser-doppler flowmetry(LDF), and LDH activity was determinated by microplate reader in vitro. Results : 1. The rCBF was significantly improved by LE(10 mg/kg, i.p.) during the period of cerebral reperfusion, compared with the control group. 2. The rCBF was significantly increased by LE after pretreatment with indomethacin(1 mg/kg, i.p.), an inhibitor of cyclooxygenase, during the period of cerebral reperfusion, compared with the LE group, and rCBF was accelerated by LE after pretreatment with methylene blue($10{\mu}g/kg$, i.p.) an inhibitor of guanylate cyclase during the period of cerebral reperfusion, compared with the control group. 3. LE significantly inhibited LDH activity in vitro in a dose-dependent manner. Conclusions : From the above results, these were suggested that Lumbricus had anti-ischemia action in connection with cyclooxygenase and might prevent the brain cells death through inhibited LDH activity.

• Journal of Korean Neurosurgical Society
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• 제29권2호
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• pp.167-179
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• 2000

Objective : We studied to clarify the effective time zone of mild hypothermic neural protection during ischemia and/or reperfusion after middle cerebral artery occlusion. Methods : In a reversible cerebral infarct model which maintained reperfusion of blood flow after middle cerebral artery occlusion for two hours, the size of cerebral infarction, cerebral edema and the extent of neurological deficit were observed and analyzed for comparison between the control and the experimental groups under hypothermia($33.5^{\circ}C$). The temporalis muscle temperature was reduced to $33.5^{\circ}C$ by surface cooling for two hours during middle cerebral artery occlusion for study group I. The following groups applied hypothermia for two-hour periods after reperfusion : group II(0-2 hours), group III(2-4 hours), and group IV(4-6 hours). They were rewarmed to $36.5^{\circ}C$ until sacrified at 2, 4, 6, 12, and 24 hours after reperfusion. Control group was maintained at normothermia without hypothermia. Results : In the experimental groups with hypothermia, the average value of the size of cerebral infarction($mean{\pm}SD$) was $1.97{\pm}1.65%$, which was a remarkable reduction over that of the control, $4.93{\pm}3.79%$. In the control, a progressive increase was shown in the size of infarction from point of reperfusion to 6 hours after reperfusion without further changes in size afterward. Intra-ischemic hypothermia(group I) prevented ischemic injury but did not prevent reperfusion injury. Group II examplified the most neural protective effect in comparison to the control group and group IV(p<0.05). The cortex was more vulnerable to reperfusion injury than the subcortex. Mild hypothermia showed more neural protective effects on the cortex than subcortex. Conclusion : The most appropriate time zone for application of mild hypothermia was defined to be within four hours following reperfusion.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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• pp.215-215
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• 1996

The present study examined chronic effects of transient focal cerebral ischemia on the substantia nigra, a remote exofocal area, using immunohistochenmical and receptor autoradiographic techniques. Transient focal cerebral ischemia was induced by middle cerebral artery (MCA) occlusion for 60 or 90 min followed by reperfusion using silicone-coated 4-0 nylon monofilament in male Wistar rats. After 1- or 2-week reperfusion following transient MCA occlusion, there were partial losses of tyrosine hydroxylase-immunoreactive dopaminergic neurons, incieases in glial fibrillary acidic protein-immunoreactive cells (gliosis), decreases in [$^3$H]YM-09151-2 binding for dopamine D$_2$ receptors, and marked atrophy in the ipsilateral substantia nigra. The precise mechanism(s) of exofocal damage to the substantia nigra is remained to be elucidated.