• The Journal of Korean Medicine
• /
• v.26 no.2 s.62
• /
• pp.217-230
• /
• 2005

Objectives: Chungpaesagan-tang (CPSGT), which is frequently used for treating patients of cerebrovascular disease, has not been reported by clinical doctors concerning the effect of neuronal aptosis caused by brain ischemia. To study the effect of CPSGT on focal cerebral ischemia in normal and diabetic rats and SHR, focal cerebral ischemia was induced by transient MCAO, and after onset CPSGT was administrated. Methods: Rats (Sprague-Dawley) were divided into four groups: sham-operated group, MCA-occluded group, CPSGT­administrated group after MCA occlusion, and normal group. The MCA was occluded by intraluminal method. CPSGT was administrated orally twice (l and 4 hours) after middle cerebral artery occlusion. All groups were sacrificed at 24 hours after the surgery. The brain tissue Was stained with $2\%$ triphenyl tetrazolium chloride (TTC) or $1\%$ cresyl violet solution, to examine effect of CPSGT on ischemic brain tissue. The blood samples were obtained from the heart.~. Tumor necrosis $factor-\alpha$ level and interleukin-6 level of serum was measured from sera using enzyme-linked immunoabsorbent assay (ELISA). Then changes of immunohistochemical expression of $TNF-\alpha$ in ischemic damaged areas were observed. Results: In NC+MCAO+CP and DM+MCAO+CP, CPSGT significantly (p<0.01) decreased the number of neuron cells compared to the control group. CPSGT markedly reduced (p<0.01) the infarct size of the forebrain in distance from the interaural line on cerebral ischemia in diabetic rats. CPSGT significantly reduced the $TNF-\alpha$ expression in penumbra region of damaged hemisphere in diabetic rats. Conclusions: CPSGT had a protective effect on cerebral ischemia in SD rats, especially in diabetic rats compared with normal SD rats.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.21 no.4
• /
• pp.891-897
• /
• 2007

This experimental Study was designed to investigate the mechanism of Acanthopanacis Cortex Roots(ACR) 50% ethyl alcohol extract on the improvement of regional cerebral blood flow and cytokines production in cerebral ischemic rats. And was designed to investigate whether ACR inhibits lactate dehydrogenase(LDH) activity in neuronal cells The results were as follows; ACR significantly inhibited LDH activity in neuronal cells. These results suggest that ACR prevents the neuronal death. rCBF was significantly and stably increased by ACR(10 mg/kg, i.p.) during the period of cerebral reperfusion, which contrasted with the findings of rapid and marked increase in control group. In cytokine production of serum by drawing from femoral arterial blood at 1 hr after middle cerebral arterial occlusion, experimental group was significantly decreased $IL-1{\beta}$ and $TNF-{\alpha}$ production, and significantly increased IL-10 production compared with control group. In cytokine production of serum by drawing from femoral arterial blood at 1 hr after reperfusion, experimental group was significantly decreased $IL-1{\beta}$ and $TNF-{\alpha}$ production, and significantly increased IL-10 production compared with control group. According to above results, the author suggest that ACR had an anti-ischemic effect through the improvement of cerebral hemodynamics, and inhibitive effect on the brain damage by inhibited $IL-1{\beta}$ and $TNF-{\alpha}$ production, and accelerated IL-10 production.

• The Journal of Internal Korean Medicine
• /
• v.24 no.2
• /
• pp.337-347
• /
• 2003

This study investigated the effect of Yanggyuksanhwa-tang on cerebral ischemia of the rats. Considering age-related impact on cerebral ischemia, aged rats (18 months old) were used for this study. Ischemic damage was induced by the transient occlusion of bilateral common carotid arteries(BCAO) under the hypotension. Yanggyuksanhwa-tang was administered twice orally. Then changes of immunohistochemical expression of c-fos and c-jun in ischemic damaged hippocampus were observed. The BCAO in aged rats led significant increase of c-fos expression in CA1 and DG of hippocampus. While the treatment of Yanggyuksanhwa-tang significantly attenuated the increase of c-fos expression in CA1 hippocampus following BCAO ischemia. Depending on changes of the normalized optical density(NOD) of immunohistochemical c-fos expression, the treatment of Yanggyuksanhwa-tang significantly attenuated the increase of NOD in CA1 and DG of hippocampus. And there was not changes in CA2 and CA3 hippocampus with respect to the control BCAO group. The BCAO in aged rats led significant increase of c-jun expression in CA1 hippocampus. While the treatment of Yanggyuksanhwa-tang significantly attenuated the increase of c-jun expression in CA1 hippocampus following BCAO ischemia. Depending on changes of the NOD of immunohistochemical c-jun expression, the treatment of Yanggyuksanhwa-tang significantly attenuated the increase of NOD in CA1 hippocampus. And there was not changes in CA2, CA3 and DG of hippocampus with respect to the control BCAO group.

• BMB Reports
• /
• v.44 no.10
• /
• pp.647-652
• /
• 2011

The protein transduction domains have been reported to have potential to deliver the exogenous molecules, including proteins, to living cells. However, poor transduction of proteins limits therapeutic application. In this study, we examined whether imipramine could stimulate the transduction efficiency of PEP-1 fused proteins into astrocytes. PEP-1-catalase (PEP-1-CAT) was transduced into astrocytes in a time- and dose-dependent manner, reducing cellular toxicity induced by $H_2O_2$. Additionally, the group of PEP-1-CAT + imipramine showed enhancement of transduction efficiency and therefore increased cellular viability than that of PEP-1-CAT alone. In the gerbil ischemia models, PEP-1-CAT displayed significant neuroprotection in the CA1 region of the hippocampus. Interestingly, PEP-1-CAT + imipramine prevented neuronal cell death and lipid peroxidation more markedly than PEP-1-CAT alone. Therefore, our results suggest that imipramine can be used as a drug to enhance the transduction of PEP-1 fusion proteins to cells or animals and their efficacies against various disorders.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.18 no.6
• /
• pp.1714-1721
• /
• 2004

This experimental study was designed to investigate the mechanism of Palmul-Tang(PMT) on the changes of cerebral hemodynamics in rats. The changes of cerebral hemodynamics in normal rats were as follows ; The PMT-induced increase in regional cerebral blood flow was significantly inhibited by pretreatment with indomethacin(1㎎/㎏, i.p.), an inhibitor of cyclooxygenase, and was inhibited by methylene blue(10㎍/㎏, i.p.), an inhibitor of guanylate cyclase. The PMT-induced dilation in pial arterial diameter was significantly inhibited by pretreatment with indomethacin and methylene blue. The PMT-induced increase in mean arterial blood pressure was significantly inhibited by pretreatment with indomethacin but was increased by methylene blue. This results were suggested that the mechanism of PMT was mediated by cyclooxygenase. The changes of cytokine production in cerebral ischemic rats were as follows ; In cytokine production of serum by drawing from femoral arterial blood after middle cerebral arterial occlusion 1hr, sample group was decreased IL-1β and TNF-α production compared with control group, IL-10 production of sample group was similar to that of control group, but sample group was significantly increased TGF-β production compared with control group. In cytokine production of serum by drawing from femoral arterial blood after reperfusion 1hr, sample group was significantly decreased IL-1β production compared with control group and decreased TNF-α production compared with control group. IL-10 production of sample group was similar to that of control group, but sample group was significantly increased TGF-β production compared with control group. In cytokine production of serum by drawing from femoral arterial blood after reperfusion 4 hrs, sample group was significantly decreased IL-1β production compared with control group, but IL-10 production of sample group was similar to that of control group. sample group was increased TNF-α and TGF-β production compared with control group. These results suggested that PMT had inhibitive effect on the brain damage by inhibiting IL-1β and TNF-α production, but by accelerating TGF-β production. The present author thought that PMT had an anti-ischemic effect through the improvement of cerebral hemodynamics and inhibitive effect on the brain damage.

• Journal of Chest Surgery
• /
• v.41 no.4
• /
• pp.405-416
• /
• 2008

Background: Spinal cord ischemic injury during thoracic and thoracoabdominal aortic surgeries remains a potentially devastating outcome despite using various methods of protection. Neuronal voltage-dependent sodium channel antagonists are known to provide neuroprotection in cerebral ischemic models. This study was designed to compare the neuroprotective effects of phenytoin with those of hypothermia in a rabbit model of spinal cord ischemia. Material and Method: Spinal cord ischemia was induced in New Zealand white rabbits by means of infrarenal aortic cross clamping for 25 minutes. Four groups of 8 animals each were studied. The control group and the hypothermia group received retrograde infusion of saline only ($22^{\circ}C$, 2 mL/min); the normothermic phenytoin group and the hypothermicphenytoin group received retrograde infusion of 100 mg of phenytoin at different rectal temperatures ($39^{\circ}C$ and $37^{\circ}C$, respectively) during the ischemic period. The neurologic function was assessed at 24 and 72 hours after the operation with using the modified Tarlov criteria. The spinal cords were harvested after the final neurologic examination for histopathological examination to objectively quantify the amount of neuronal damage. Result: No major adverse effects were observed with the retrograde phenytoin infusion during the aortic ischemic period. All the control rabbits became severely paraplegic, Both the phenytoin group and the hypothermia group had a better neurological status than did the control group (p < 0.05). The typical morphological changes that are characteristic of neuronal necrosis in the gray matter of the control animals were demonstrated by means of the histopathological examination, whereas phenytoin or hypothermia prevented or attenuated these necrotic phenomena (p < 0.05). The number of motor neuron cells positive for TUNEL staining was significantly reduced, to a similar extent, in the rabbits treated with phenytoin or hypothermia. Phenytoin and hypothermia had some additive neuroprotective effect, but there was no statistical significance between the two on the neurological and histopathological analysis. Conclusion: The neurological and histopathological analysis consistently demonstrated that both phenytoin and hypothermia may afford significant spinal cord protection to a similar extent during spinal cord ischemia in rabbits, although no significant additive effects were noticed.

• Journal of Chest Surgery
• /
• v.31 no.10
• /
• pp.945-951
• /
• 1998

Background: Although profound hypothermia with total circulatory arrest(TCA) is a valuable maneuver in cardiac surgery, its applications have been limited due to serious complications, especially cerebral damage. In this study, the possible role of creatinine kinase-BB(CK-BB), an index enzyme of ischemic cerebral damage, was assayed as a parameter for the assessment of the cerebral complications after TCA. Hemoglobin(Hb), ionized calcium(Ca++), and blood glucose levels were also assessed as clinical parameters involved in cerebral damage. Materials and methods: Among patients with congenital heart disease, 18 patients who had been operated on with TCA were randomly selected and divided into two groups: 6 with acyanotic and 12 with cyanotic heart disease. Arterial blood from each patient was collected before and after TCA at scheduled times(15 min., 30 min, 1, 2, 4, 8, and 12hr). The levels of CK-BB, Hb, Ca++, and blood glucose were assessed in each sample. Results: As a whole, correlation between CK-BB level and blood sampling time after TCA was not statistically significant. Also, the difference in the level of CK-BB after TCA was not significant between the acyanotic and cyanotic groups. The levels of Hb and CK-BB correlated significantly. Conclusions: The results, which showed no correlation between the alterations in CK-BB level and the TCA duration, suggest that the single assay of the CK-BB level is not a representative measurement for the assessment of cerebral damage after TCA. Also, the cyanotic congenital heart disease group is not more vulnerable to cerebral damage induced by TCA.

• The Journal of Korean Medicine
• /
• v.22 no.1
• /
• pp.78-89
• /
• 2001

Objectives : The purpose of this investigation is to evaluate the effects of Woohwangcheongsim-won on reperfusion following MCA occlusion in rats. Methods : To evaluate the effect of Woohwangcheongsim-won on reperfusion following MCA occlusion, the volume of cerebral ischemia and edema were measured and the change of the CAI pyramidal neuron in the hippocampus was investigated by light microscopy. And the changes of several neurotransmitters and enzymes were investigated with the immunohistochemical methods. Results : 1. The volume of the control group, which was ischemic-damaged was 23.6%, and that of the sample group was 13.5%. 2. The voluminalratio of the right/left hemisphere was 116 in the control group, and that of the sample group was 107. 3. The pyramidal cells of CAI area in the control group were greatly damaged. The cells were changed into discontinuous and unsystematic forms, and nuclei, and cytoplasms were shrunk. On the other hand, the cells of the sample group were less damaged. 4. On the immunohistochemical methods, the sensitivities of GABA, NOS, DBH in the control group were increased, and those of synapsin and $eEF-l{\alpha}$ were decreased as compared with the normal group. NOS and DBH which were negative in the normal group showed positive reaction. On the other hand, the sensitivities of GABA, NOS and DBH in the sample group were decreased, but those of NPY, synapsin, CaMKII and $eEF-l{\alpha}$ were increased as compared with the control group. Conclusions : Woohwangcheongsim-won reduced the volume of cerebral ischemia and edema, and minimized the damage of pyramidal cells. The mechanism was related to protein synthesis, such as synapsin, ${\alpha}CaMKII$ and $eEF-l{\alpha}$, which resist neurotoxicity of glutamate receptors.

• Journal of International Academy of Physical Therapy Research
• /
• v.1 no.2
• /
• pp.107-112
• /
• 2010

The majority of strokes are caused by ischemia and result in brain tissue damage, leading to problems of the central nervous system including hemiparesis, dysfunction of language and consciousness, and dysfunction of perception. The purpose of this study was to investigate the effects of Poly(ADP-ribose) polymerase(PARP) on necrosis in neuronal cells that have undergone needle electrode electrical stimulation(NEES) prior to induction of ischemia. Ischemia was induced in male SD rats(body weight 300g) by occlusion of the common carotid artery for 5 min, after which the blood was reperfused. After induction of brain ischemia, NEES was applied to Zusanli(ST 36), at 12, 24 and 48 hours. Protein expression was investigated using immuno-reactive cells, which react to PARP antibodies in cerebral nerve cells, and Western blotting. The results were as follows: In the cerebral cortex, the number of PARP reactive cells after 24 hours significantly decreased(p<.05) in the NEES group compared to the GI group. PARP expression after 24 hours significantly decreased(p<.05) in the NEES group compared to the GI group. As a result, NEES showed the greatest effect on necrosis-related PARP immuno-reactive cells 24 hours after ischemia, indicating necrosis inhibition, blocking of neural cell death, and protection of neural cells. Based on the results of this study, NEES can be an effective method of treating dysfunction and improving function of neuronal cells in brain damage caused by ischemia.

• Journal of Ginseng Research
• /
• v.31 no.1
• /
• pp.44-50
• /
• 2007

Ginseng powerfully tonifies the original Qi. Ginseng used for insomnia, palpitations with anxiety, restlessness from deficient Qi and blood and mental disorientation. In order to investigate whether Ginseng cerebral ischemia-induced neuronal and cognitive impairments, we examined the effect of Ginseng on ischemia-induced cell death in the hippocampus, and on the impaired learning and memory in the Morris water maze and passive avoidance in rats. Ginseng when administered to rat at a dose of 200 mg/kg i.p. water extracts to 0 minutes and 90 minutes after 4-VO, significantly neuroprotective effects by 86.4% in the hippocampus of treated rats. For behavior test, rats were administered Ginseng (200mg/kg p.o.) daily for two weeks, followed by their training to the tasks. Treatment with Ginseng produced a marked improvement in escape latency to find the platform in the Morris water maze. Ginseng reduced the ischemia-induced learning disability in the passive avoidance. Consistent with behavioral data, treatments with Ginseng reduced jschemia-induced cell death in the hippocampal CA1 area. Oxidative stress is a causal factor in the neuropathogenesis of ischemic-reperfusion injury. Oxidative stress was examined in a rat model of global brain ischemia. The effects of Ginseng on lipid peroxidation (inhibition of the production of malondialdehyde, MDA) in different regions of the rat brain were studied. Ferrous sulfate and ascorbic acid (FeAs) were used to induce lipid peroxidation. The antiperoxidative effect showed 48-72% protection from tissue damage as compared with untreated animals. These results showed that Ginseng have a protective effect against ischemia-induced neuronal loss and learning and memory damage.