• The Korean Journal of Physiology and Pharmacology
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• v.8 no.4
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• pp.187-194
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• 2004

Middle cerebral artery occlusion (MCAO) results in cell death by activation of complex signal pathways for cell death and survival. Hypothermia is a robust neuroprotectant, and its effect has often been attributed to various mechanisms, but it is not yet clear. Upstream from the cell death promoters and executioners are several enzymes that may activate several transcription factors involved in cell death and survival. In this study, we immunohistochemically examined the phosphorylation of mitogen-activated protein kinase, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 kinase during early period of the ischemic injury, following 2 hours (h) of transient MCAO. Increased phosphorylation of ERK and p38 was observed in the vessels at 3 h, neuron-like cells at 6 and 12 h and glia-like cells at 12 h. Activation of JNK was not remarkable, and a few cells showed active JNK following ischemia. Phosphorylation of Elk-1, a transcription factor, was reduced by ischemic insult. Hypothermia attenuated the activation of ERK, p38 and JNK, and inhibited reduction of Elk-1. These data suggest that signals via different MAPK family members converge on the cell damage process and hypothermia protects the brain by interfering with these pathways.

• The Korean Journal of Physiology
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• v.28 no.2
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• pp.191-196
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• 1994

Captopril, an inhibitor of angiotensin converting enzyme, is also known to inhibit the degradation of bradykinin. We examined the effects of intracerebroventricular (ICV) captopril on the central pressor response to bradykinin in normotensive, 2-kidney, 1 clip Goldblatt (GHR) and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Captopril (1 mg) and bradykinin (5 nmol) were administered into the right lateral cerebral ventricle, and blood pressure and heart rate were continuously monitored throughout the experiment. ICV captopril alone did not affect the blood pressure within 10 minutes but it significantly augmented the central pressor response to bradykinin in GHR. On the contrary, captopril was without effect on the pressor response to bradykinin in normotensive and DOCA-salt rats. These findings indicate that endogenous kinins are not critical in regulating arterial pressure in normotensive and DOCA hypertensive rats. However, in GHR, an enhanced activity of the brain kallikrein-kinin system in maintaining the high blood pressure is suggested.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.4
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• pp.363-368
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• 2018

Hypotension is one of the potential causes of dizziness. In this review, we summarize the studies published in recent years about the electrophysiological and pharmacological mechanisms of hypotension-induced dizziness and the role of the vestibular system in the control of blood pressure in response to hypotension. It is postulated that ischemic excitation of the peripheral vestibular hair cells as a result of a reduction in blood flow to the inner ear following hypotension leads to excitation of the central vestibular nuclei, which in turn may produce dizziness after hypotension. In addition, excitation of the vestibular nuclei following hypotension elicits the vestibulosympathetic reflex, and the reflex then regulates blood pressure by a dualcontrol (neurogenic and humoral control) mechanism. In fact, recent studies have shown that peripheral vestibular receptors play a role in the control of blood pressure through neural reflex pathways. This review illustrates the dual-control mechanism of peripheral vestibular receptors in the regulation of blood pressure following hypotension.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.1
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• pp.50-56
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• 2009

The present study was designed to investigate the effects of Phamacopuncture therapy using Cervi Pantotrichum Cornu (PC) at BL23 BL52 on the regional cerebral blood flow (rCBF) and mean arterial blood pressure (MABP) in normal rats, then the related mechanisms were also investigated. In addition, the present author also investigated the effects of phamacopuncture therapy at BL23.BL52 on the rCBF in cerebral ischemic rats. The results in normal rats were as follows; PC (3 mg/kg and 5 mg/kg) at BL23 BL52 significantly increased rCBF but decreased MABP. This result suggests that PC at BL23 BL52 significantly increased rCBF by dilating pial arterial diameter. Increase of PC (5 mg/kg)-induced rCBF was significantly inhibited by pretreatment with indomethacin (1 mg/kg, i.p.), an inhibitor of cyclooxygenase and methylene blue ($10{\mu}g/kg$, i.p.), an inhibitor of guanylate cyclase. Decrease of PC (5 mg/kg)-induced MABP was significantly increased by pretreatment with methylene blue but was decreased by pretreatment with indomethacin. These results suggested that the action of PC (5 mg/kg) was mediated by guanylate cyclase. The results in cerebral ischemic rats were as follows ; The rCBF was significantly and stably increased by PC (5 mg/kg) during the period of cerebral reperfusion, which contrasted with the findings of rapid and marked increase in Control group. In conclusion, these results suggest that phamacopuncture therapy using Carthami flos at BL23 BL52 can increase rCBF in normal state, and improve stability of rCBF in ischemic state. In addition, the present author also suggest that related mechanisms are involved in guanylate cyclase pathway.

• Journal of Korean Neurosurgical Society
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• v.40 no.4
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• pp.267-272
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• 2006

Objective : There have been recent reports that mesenchymal stromal cells that are harvested from adipose tissue are able to differentiate into neurons. In the present study, we administered adipose tissue derived stem cells in rats with cerebral infarction in order to determine whether those stem cells could enhance the recovery of motor function. Methods : Cerebral infarction was induced by intraluminal occlusion of middle cerebral artery in rats. The adipose tissue-derived mesenchymal stem cells were harvested from inguinal fat pad and proliferated for 2 weeks in DMEM media. Approximately $1{\times}10^6$ cells were injected intravenously or into subdural space of the peri-lesional area. The rotor rod test was performed at preoperative state[before MCA occlusion], and 1, 2, 3, 4, 6, 8 and 10 weeks after the cell therapy. Results : The motor functions that were assessed by rotor rod test at 1 week of the cell therapy were nearly zero among the experimental groups. However, there was apparent motor function recovery after 2 weeks and 4 weeks of cell injection in intravenously treated rats and peri-lesionaly treated rats, respectively, while there was no significant improvement till 8 weeks in vehicle treated rats. Conclusion : These results demonstrate that the adipose derived stem cell treatment improves motor function recovery in rats with cerebral infarction.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.3
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• pp.575-580
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• 2006

This Study was designed to investigate the effects of Mixture of Bambusae Caulis in Liquamen and Bamboo Extract on the change of regional cerebral blood flow (rCBF) and mean arterial blood pressure (MABP) in normal and cerebral ischemic rats. Experimental materials were as follows ; BE- 1 was Bamboo Extract (BE) extracted with 70% ethyl alcohol, BE-11 was BE extracted with distilled water at $121^{\circ}C$ for 30 min, BE-111 was BE extracted with distilled water at $121^{\circ}C$ for 3 hrs, MLC was mixture of Bambusae Caulis in Liquamen (BCL) and BE-111 mixed at the ratio of 1 to 100 (MLC100), 1 to 50 (MLC50), 1 to 20 (MLC20), 1 to 10 (MLC10), 1 to 5 (MLC5). The results were as follows , The Changes of BE- 1 on the rCBF and MABP in normal rats were not showed, BE- 11 significantly decreased rCBF in a dose-dependent manner Dut increased MABP in a dose-dependent manner. BE-111 increased rCBF in a dose-dependent manner, MLC significantly increased rCBF in a dose-dependent manner and increased MABP in a dose-dependent manner. rCBF was significantly and stably increased by MLC5 (1 mg/kg, i.p.) during the period of cerebral reperfusion, which contrasted with the findings of rapid and marked increase in control group. As results above ; The present author thought that BE- 111 and MLC increased rCBF by dilating pial arterial diameter.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.6
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• pp.643-650
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• 2017

Vascular dementia (VaD) is a group of heterogeneous diseases with the common feature of cerebral hypoperfusion. To identify key factors contributing to VaD pathophysiology, we performed a detailed comparison of Wistar and Sprague-Dawley (SD) rats subjected to permanent bilateral common carotid artery occlusion (BCCAo). Eight-week old male Wistar and SD rats underwent BCCAo, followed by a reference memory test using a five-radial arm maze with tactile cues. Continuous monitoring of cerebral blood flow (CBF) was performed with a laser Doppler perfusion imaging (LDPI) system. A separate cohort of animals was sacrificed for evaluation of the brain vasculature and white matter damage after BCCAo. We found reference memory impairment in Wistar rats, but not in SD rats. Moreover, our LDPI system revealed that Wistar rats had significant hypoperfusion in the brain region supplied by the posterior cerebral artery (PCA). Furthermore, Wistar rats showed more profound CBF reduction in the forebrain region than did SD rats. Post-mortem analysis of brain vasculature demonstrated greater PCA plasticity at all time points after BCCAo in Wistar rats. Finally, we confirmed white matter rarefaction that was only observed in Wistar rats. Our studies show a comprehensive and dynamic CBF status after BCCAo in Wistar rats in addition to severe PCA dolichoectasia, which correlated well with white matter lesion and memory decline.

• Journal of Sasang Constitutional Medicine
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• v.13 no.2
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• pp.165-176
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• 2001

This study demonstrates the effects of Yanggyuksanhwa-Tang, Sasang constitutional herb prescription reported its clinical effect on the stroke of the So-yang In(少陽人), on the cerebral blood flow changes induced by nitro L-arginine methyl ester (L-NAME) treatment and ischemic brain damage induced by the middle cerebral artery occlusion (MCAO) in the rats. The changes of the arterial blood pressure, cerebral blood flow, and the diameter of the pial artery were measured in rats treated with L-NAME. And the changes of the infarct size, volume, and plasma tumor necrosis factor alpha ($TNF-{\alpha}$) levels were measured in the rats that the middle cerebral artery has been occluded by the intraluminal suture thread method. Yanggyuksanhwa-Tang was administered by the i.v. injection on the L-NAME treated rats, by the i.o. administration on the MCAO rats. The results is 1. The changes of the arterial blood pressure was not different statistically between in the L-NAME treated control group and in the Yanggyuksanhwa-Tang administered group. 2. Increase in the cerebral blood flow induced by L-NAME treatment was attenuated in the Yanggyuksanhwa-Tang administered group significantly (P<0.05) as compared with the L-NAME treated control group. 3. Decrease in the diameter of the pial artery induced by L-NAME treatment was attenuated about 18% in the Yanggyuksanhwa-Tang administered group as compared with the L-NAME treated control group. 4. Ischemic damaged infarct areas were decreased significantly (P<0.05) in the interaural 12mm, 10mm, and 6mm brain sections of the Yanggyuksanhwa-Tang administered group as compared the MCA occluded control group. 5. Total ischemic infarct volume was decreased significantly (P<0.05) in the Yanggyuksanhwa-Tang administered group as compared the MCA occluded control group. 6. Plasma $TNF-{\alpha}$ levels were decreased significantly (P<0.01) in the Yanggyuksanhwa-Tang administered group as compared the MCA occluded control group.

• Animal cells and systems
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• v.15 no.4
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• pp.279-286
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• 2011

Hypoxic ischemia injury is a common cause of functional brain damage, resulting from a decrease in cerebral blood flow and oxygen supply to the brain. The main problems associated with hypoxic ischemia to the brain are memory impairment and dopamine dysfunction. Hypothermia has been suggested to ameliorate the neurological impairment induced by various brain insults. In this study, we investigated the effects of hypothermia on memory function and dopamine synthesis following hypoxic ischemia to the brain in rats. For this purpose, a step-down avoidance task, a radial eight-arm maze task, and immunohistochemistry for tyrosine hydroxylase (TH) and 5-bromo-2'-deoxyuridine (BrdU) were performed. The present results indicated that the hypoxic ischemia-induced disturbance of the animal's performances and spatial working memory was associated with a decrement in TH expression in the substantia nigra and striatum, and an increase in cell proliferation in the hippocampal dentate gyrus. Hypothermia treatment improved the animals' performance and spatial working memory by suppressing the decrement in TH expression in the substantia nigra and striatum and the increase in cell proliferation in the dentate gyrus. We suggest that hypothermia can be an efficient therapeutic modality to facilitate recovery following hypoxic ischemia injury to the brain, presumably by modulating the dopaminergic cell loss.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.1
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• pp.236-242
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• 2004

Cerebral ischemia resulting from transient or permanent occlusion of cerebral arteries leads to neuronal cell death and eventually causes neurological impairments. Bee venom has been used for the treatment inflammatory disease. In the present study, the effects of bee venom on apoptosis and cell proliferation in the hippocampal dentate gyrus following transient global ischemia in gerbils were investigated using immunohistochemistry for cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), caspase-3, and 5-bromo-2'-deoxyuridine (BrdU). It was shown that apoptotic cell death and cell proliferation in the hippocampal dentate gyrus were significantly increased following transient global ischemia in gerbils and that treatment of bee venom suppressed the ischemia-induced increase in apoptosis and cell proliferation in the dentate gyrus. The present results also showed that 1 mg/kg bee-venom treatment suppressed the ischemia-induced increasing apoptosis, cell proliferation, and COX-2 expression in the dentate gyrus. It is possible that the suppression of cell proliferation is due to the reduction of apoptotic cell death by treatment of bee venom. In the present study, bee venom was shown to prosses anti-apoptotic effect in ischemic brain disease, and this protective effect of bee venom against ischemia-induced neuronal cell death is closely associated with suppression on caspase-3 expression.