• The Korean Journal of Zoology
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• v.31 no.3
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• pp.191-206
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• 1988

Chick embryos which have received a single injection of the organophosphate compound,malathion (0.1 mg, 0.5 mg, 1.0 mg or 2.0 mg in 0.05 ml of corn oil) via the yolk sac at certain times (2 daya, 4 days or 6 days after incubation) have been investigated. After 9 days of incubation, chick embryos were harvested to investigate the effects of malathion on the development of cerebrum morphologically and biochemically. The effects of simultaneous injection of malathion and nicotinamide were also compared. On ultrastructural examination, neurons in cerebral cortex showed to be inhibited in their differentiation by malathion; nuclear irregularity, swelling of endoplasmic reticulum, and cytoplasmic vacuoles were observed. On cytochemical study of acetylcholinesterase(AChE) by electron microscope, the positive reaction products of this enryme were localized at the membrane of nucleus and endoplasmic reticulum of neurons. Inhibition of AChE activty was severe in groups treated with relatively low doses, which was consistent with the results of spectrophotometric analysis. The activity of lactate dehydrogenase(LDH) of cerebrum in groups treated with malathion was higher than that of the control group. The nicotinamide adenine dinucleotide(NAD) content of chick embruo treated with malathioti decreased significantly, and nicotinamide coinjection raised the NAD level as compared with the control group, thus preventing malathion-induced momhological alteration. In conclusion, it is suggested that malathion changes the ultrastructure of differentiating neurons and alters some enzyme activities in chick embryo cerebrum, and the severity of which is consistently dose-or age-dependent.

• The Journal of Internal Korean Medicine
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• v.22 no.2
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• pp.161-174
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• 2001

Objectives : The purpose of this investigation is to evaluate the effect of Chungpesagan-Tang Extracts on reversible forebrain ischemia in Sprague-Dawley rats. Methods : the volume of cerebral infarction and edema, the pathohistological change of neurons, the number of survived neurons, neurotransmitters through immunohistochemical methods, proteins connected with neurotransmitters through immunohistochemical methods and the pathohistological change of neurons through electro-microscopy were investigated. From these reseach data, the protection of neurons and the activity of brain cells were examined. Results : 1. The infaction volume of the control group was 23.9%, and that of the sample group was 16%. 2. The brain edema volume of the control group increased by 17% compared to the normal group and that of the sample group increased by 10%. 3. The light microscopy revealed that the neurons in the ischemia-induced area and CA1 area of hippocampus were most heavily damaged and that the sample group was less damaged compared with the control group. Most pyramidal neurons died in 7 days when brain ischemia was induced. 4. The number of survived pyramidal neurons in the CA1 area of the hippocampus were studied. The normal group had 93 neurons/mm, survived the control group(after 3 days) had 21/mm, the control group(after 7 days) had 3/mm and the sample group 33/mm. 5. The immunohistochemical methods revealed that: (1) In the control group, the sensitivity of GABA, NOS, DBH were increased, and those of Synapsin, eEF-$1{\alpha}$ decreased. NOS and DBH had positive reactions in the control group, but negative in the normal group. (2) In thd sample group, the sensitivity of GABA, NOS, DBH were attenuated, and those of NPY, Synapsin, CaMKII, eEF-$1{\alpha}$ increased when compared to the control group. 6. The electro-microscopy revealed that most neurons died by necrosis and some neurons died by apoptosis. Several imflammation cells appeared in the injured area of neurons. The number of neurons in the sample group that died by ischemia decreased. But, the number that died by apoptosis did not significantly change. Conclusions : The data shows that the effect of Chungpesagan-Tang Extracts on reversible forebrain ischemia in Sprague-Dawley rats is significant.

• Journal of Oriental Neuropsychiatry
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• v.19 no.1
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• pp.125-146
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• 2008

Objectives : The purpose of this study is to suggest for the following experimental study of dementia by reviewing recent oriental medicine journals that have been published since 2000. Methods: We have investigated various types of studies in relation to dementia through 90 articles that have been published from 2000 to 2007 in recent oriental medicine journals were registered Korea research foundation. Results and Conclusions : 1. Since 2000, 88 articles in relation to dementia have been published and almost of them are herbal medicine-centered studies. Also they show a tendency to increase every year. The journal of oriental neuropsychiatry carries the highest number of studies in relation to dementia. 2. According to the experimental paper, there are 30 cases of using herb simplexes, 48 cases of herb-combined prescription, and 10 cases of other ways. Especially 7 cases of using herb-combined prescription relation to Sasang constitution are all for the Taeumin. 3. There are 85 cases of Animal and cellular experimental, 60 cases of using pathologic model induced cytotoxic activity, a case of using L-NAME, 3 cases of 192 saporin, 4 cases of ibotenic acid, 10 cases of focal cerebral ischemia, 3 cases of alcohol-administered, and one case of natural degradation. 4. Moms water maze, Radial arm maze Passive avoidance learning model were using for examining learning and memory of model animal 5. We propose that following studies of dementia are to he investigated of the applied method of using siRNA with tranceduced gene, sample preparation by water-soaking, oriental medical diagnosis, standardization of differentiating symptom and herb simplexes, building the database by classified prescriptions, and experiment model which are based on precise examining mechanism with cell line as like mouse H19-7 hippocampus, rat HT22 hippocampus, astrocyte, microglia, using the model of animals at APP, PS1, BACE, CT99/PS1, APOE4, Tau, APP/PSI/Tau

• The Korea Journal of Herbology
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• v.33 no.2
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• pp.69-77
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• 2018

Objectives : Daesiho-tang (DSHT) has been widely used in the treatment of cerebral infarct in traditional medicine. However, there was not report on the anti-obesity-related diseases efficacy of DSHT. In this study, we investigated the effects for the new formulation of DSHT, on the adipocyte differentiation cycle in 3T3-L1 cells. Methods : 3T3-L1 cells were treated with DSHT (50, 100, $200{\mu}g/m{\ell}$) during differentiation for 6 days. Also, the inhibitory effect of DSHT against 3T3-L1 adipogenesis was evaluated in various stage of adipogenesis such as early (0-2day), intermediate (2-4day), and terminal stage (4-6day). The accumulation of lipid droplets was determined by Oil Red O staining. and, the expressions of genes related to adipogenesis were measured by RT-PCR and Western blot analyses. Results : DSHT showed inhibitory activity on adipocyte differentiation at 3T3-L1 preadipocytes without affect cell toxicity as assessed by measuring fat accumulation and adipogenesis. In addition, DSHT significantly reduced the expression levels of several adipocyte marker genes including proliferator activated $receptor-{\gamma}$ ($PPAR-{\gamma}$) and CCAAT/ enhancer-binding $protein-{\alpha}$ ($C/EBP-{\alpha}$). Also, the anti-adipogenic effect of DSHT was strongly limited in the intermediate (2-4 day), terminal stage (4-6 day) of 3T3-L1 adipogenesis. In addition, the DSHT treatment down- regulated mRNA expression levels of $PPAR-{\gamma}$,, $C/EBP-{\alpha}$ in mature 3T3-L1 adipocytes. Conclusions : These results suggest that, the ability of DSHT has inhibited overall adipogenesis and lipid accumulation in the 3T3-L1 cells. The new formulation of DSHT may be a promising medicine for the treatment of obesity and related metabolic disorders.

• The Korea Journal of Herbology
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• v.24 no.1
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• pp.179-189
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• 2009

Objectives : Coptidis Rhizoma (Coptis japonica MAKINO; CR) is a well known crude drug as antimicrobial, antibacterial, anti-inflammatory, antioxidant activity. However, there is no study of the effect of CR on brain infarction and it's mechanism. The aim of this study was to investigate the effects on ischemic stroke induced by photothrombotic infarction by evaluating the functional & neuronal recovery after brain infarction. Materials & Methods : Male Sprague-Dawley rats (250-300 g) were induced photothrombotic brain infarction on sensorimotor cortex, and brain infarction volume by image J software (NIH, USA) after Nissl stain, also single pellet reaching task as a functional motor recovery were observed. After orally pretreated by CR (500 mg/kg) or normal saline as a sham control before 7 days from the time of photothrombotic infarction, rats were sacrificed. After then we analysed anti-inflammatory cytokines (TNF-$\alpha$, IL-6, IL-1$\beta$), by RT-PCR and ELISA method, and immunohistochemistry (GFAP, connexin-43) as a marker of neural plasticity. Results : CR (100, 250, 500 mg/kg) decreased the infarction volume dose-dependently, however the effect of 500mg/kg of CR (CR 500) showed the best (P=0.051). Also, CR 500 decreased the infarction volume time-dependently, the most effective time was 3-7 days after stroke. Photothrombosis increased inflammatory cytokines after infarction, CR 500 suppressed significantly mRNA expression of IL-1$\beta$, IL-6 and TNF-$\alpha$. In serum, CR 500 decreased the amount of IL-1$\beta$, 12h, 24h and 48h respectively (p < 0.05), also decreased that of IL-6 and TNF-$\alpha$, 12h respectively (p < 0.05) after infarction. The more astrocytes were observed and neural plasticity was facilitated in the rat brain of CR 500 than that of sham control in immunohistochemistry. Conclusions : This results suggest that CR decrease infarction volume and improve functional motor recovery in acute stage in photothrombotic ischemic infarction model in the mechanism of anti-inflammation and promoting neural plasticity.

• The Korean Journal of Pharmacology
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• v.32 no.3
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• pp.323-334
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• 1996

Male Mongolian gerbils $(60{\sim}80g)$ were given DL-difluoromethylornithine (DFMO; 250mg/kg, ip) and methylglyoxal bis(guanylhydrazone) (MGBG; 50 mg/k, ip), respectively, 1 h prior to transient (7 min) occlusion of bilateral common carotid arteries (OBC7) and a daily dose of one of them for 6 days after recirculation, and the polyamine contents, activities of ornithine and S-adenosylmethionine decarboxylases (ODC and SAM-DC), and light microscopic findings of the hippocampus were evaluated. The hippocampal putrescine (PT) levels of the control gerbils treated with saline (STGr), markedly increased after OBC7, showing a peak level at 24 h after recirculation. The peak PT level was reduced in DFMO treated gerbils (DTCr) and in MGBG treated gerbils (MTGr). And 7 days after recirculation, the PT level of DTGr was decreased to about 75% of the PT level in the sham operated group (nonTGr) and to about 55% of the STGr level, respectively. The hippocampal spermidine (SD) level of STGr tended to decline, showing the lowest value at 8 h after recirculation. But the spermidine (SD) level of DTGr was somewhat higher at 8 h after OBC7 than those of STGr and MTGr The hippocampal spermine (SM) levels of all the experimental groups were little changed for 7 days after OBC. OBC7 markedly increased the hippocampal ODC activity. reaching a maximum (about 3 times higher than preischemic level) at 8 h and rapidly recovered to the control value by 24 h in STGr gerbils, and the OBC7-induced increase of ODC activity was significantly attenuated by DFMO or MGBG treatment. Whereas OBC7 induced a rapid decrease of the hippocampal SAMDC activity follwed by gradual recovery to the preischemic level, and the decrease of the SAMDC activity was slightly attenuated by DFMO or MGBG treatment. 7 Days after OBC7 the histological finding of the hippocampal complex stained with cresyl violet showed an extensive delayed neuronal damage in the CA1 region and to a lesser extent, in the dentate gyrus, sparing the CA3 region. And the neuronal death was aggevated by DFMO but significantly attenuated by MGBG. The immunochemical reactivity of hippocampus to anti-GFAP antibody was significantly increased in the CA1 region and to a lesser extent, in the dentate gyrus 7 days after OBC7, but was little changed in the CA3. And the increase of the anti-GFAP immunoreactivity was moderately enhanced by DFMO and significantly suppressed by MGBG. These results suggest that the polyamine metabolism may play a modulatory role in the ischemic brain damage.

• The Korean Journal of Nuclear Medicine
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• v.32 no.6
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• pp.482-489
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• 1998

Purpose: Radionuclide cisternography may be helpful in understanding pathophysiology of postural head-ache and low CSF pressure in patients with spontaneous intracranial hypotension. The purpose of this study was to characterize radionuclide cisternographic findings of spontaneous intracranial hypotension. Materials and Methods: The study population consists of 15 patients with spontaneous intracranial hypotension. Diagnosis was based on their clinical symptoms and results of lumbar puncture. All patients underwent radionuclide cisternography following injection of 111 to 222 MBq of Tc-99m DTPA into the lumbar subarachnoid space. Sequential images were obtained between 112 hour and 24 hour after the injection of Tc-99m DTPA. Radioactivity of the bladder, soft tissue uptake, migration of radionuclide in the subarachnoid space, and extradural leakage of radionuclide were evaluated according to the scan time. Results: Radionuclide cisternogram showed delayed migration of radionuclide into the cerebral convexity (14/15), increased soft tissue uptake (11/15), and early visualization of bladder activity at 30min (6/10) and 2hr (13/13). Cisternography also demonstrated leakage site of CSF in 4 cases and 2 of these were depicted at 30min. Epidural blood patch was done in 11 patients and headache was improved in all cases. Conclusion: The characteristic findings of spontaneous intracranial hypotension were delayed migration of radionuclide and early visualization of the soft tissue and bladder activity. These scintigraphic findings suggest that CSF leakage rather than increased CSF absorption or decreased production may be the main pathophysiology of spontaneous intracranial hypotension. Early and multiple imaging including the bladder and soft tissue is required to observe the entire dynamics of radionuclide migration.

• Proceedings of the Ginseng society Conference
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• 1988.08a
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• pp.92-98
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• 1988

The present study was performed to find the effects of ginseng and its saponins. which is written in Chung Yao Ta Tsu Tien as anti-amnesia in its chief indication. on experimental amnesia in mice. In the step through test. ginsenoside $Rb_1\;(GRb_1)\;and\;GRg_1$ facilitated the registration of memory and antagonized the electroconvulsive shock (ECS)-induced inhibition of the retention of memory. Moreover. $GRg_1$ antagonized the EtOH-induced inhibition of the retrieval of memory. In the step down test. $GRb_1\;GRb_2\;and\;GRg_1$ antagonized the ECS-induced inhibition of the retention of memory. Moreover. $GRg_1$ antagonized the EtOH-induced inhibition of the retrieval of memory and facilitated the acquisition of short term memory. In the shuttle hox and lever press tests. they have no effects on acquisition and retrieval of memory. except $GRb_1\;GRb_1$ depressed the retrieval of conditioned avoidance response in the shuttle box test. After the end of four tests. the effects of these orally administered drugs on sedative. analgesic. antipyretic and anticonvulsant actions. and on spontaneous and exploratory movements were tested in doses of less than 500mg/kg. but they had none of these effects. Present study may indicate that $GRg_1$ had effects on the retrieval of memory and on the acquisition process of learning response. The recent research on the role of NGF for the survival. regeneration and regulation of brain in adult animals. indicated the importance of NGF on dementia and amnesia. During our research on the specificity of the neurite out growth induced by NGF. we found that the effect of NGF was potentiated by $GRb_1$ in organ cultures of chick embryonic dorsal root ganglia. Then. the effect of $GRb_1$ on neuronal cell survivalin cell culture system was studied. $GRb_1$ potentiated the NGF-mediated increase of neurofilaments in cell cultures of chick embryonic sensory and sympathetic neurons. NGF with $GRb_1$ also showed a tendency to increase the number of surviving neurons of rat embryonic cerebral cortex. NGF increased choline acetyl transferase activity in cell cultures of rat embryonic septum area neurons. but $GRb_1$ did not potentiate NGF activity in cell cultures of rat embryonic septum area neurons. Present study may indicate that $GRb_1$ plays an important role for the survival or regeneration of neurons in the brain.

• Clinical and Experimental Pediatrics
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• v.52 no.7
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• pp.824-831
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• 2009

Purpose : We aimed to investigate the efficacy of and functional recovery after intracerebral transplantation of different doses of mouse mesenchymal stem cells (mMSCs) in immature rat brain with hypoxic-ischemic encephalopathy (HIE). Methods : Postnatal 7-days-old Sprague-Dawley rats, which had undergone unilateral HI operation, were given stereotaxic intracerebral injections of either vehicle or mMSCs and then tested for locomotory activity in the 2nd, 4th, 6th, and 8th week of the stem cell injection. In the 8th week, Morris water maze test was performed to evaluate the learning and memory dysfunction for a week. Results : In the open field test, no differences were observed in the total distance/the total duration (F=0.412, P=0.745) among the 4 study groups. In the invisible-platform Morris water maze test, significant differences were observed in escape latency (F=380.319, P<0.01) among the 4 groups. The escape latency in the control group significantly differed from that in the high-dose mMSC and/or sham group on training days 2-5 (Scheffe's test, P<0.05) and became prominent with time progression (F=6.034, P<0.01). In spatial probe trial and visible-platform Morris water maze test, no significant improvement was observed in the rats that had undergone transplantation. Conclusion : Although the rats that received a high dose of mMSCs showed significant recovery in the learning-related behavioral test only, our data support that mMSCs may be used as a valuable source to improve outcome in HIE. Further study is necessary to identify the optimal dose that shows maximal efficacy for HIE treatment.

• Journal of Korean Neurosurgical Society
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• v.29 no.10
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• pp.1309-1315
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• 2000

Objectives : We performed an in vivo experiment to investigate the effect of $^{166}Holmium$ and $^{166}Holmium$-chitosan complex($^{166}Ho$-CHICO) on the normal brain of rats and to determine the sublethal dose of $^{166}Ho$-CHICO. Materials and Methods : $^{166}Ho$ is a beta and gamma ray emitter. $^{166}Ho$-CHICO is a novel radio-pharmaceutical complex with chitosan to facilitate the transport of $^{166}Ho$ obtained from Korea Atomic Energy Research Center(Taejon, Korea). It is in acidic form and becomes gel state at alkaline pH. One hundred and seventy consecutive rats were divided into four groups : $^{166}Ho$ treated(n＝50), $^{166}Ho$-CHICO treated(n＝57), saline treated(n＝5) and chitosan treated(n＝5) groups. $^{166}Ho$ and $^{166}Ho$-CHICO were injected into the rat brain stereotactically with various doses of 0.1mCi/$20{\mu}l$, 0.2mCi/$20{\mu}l$, 0.3mCi/$20{\mu}l$, and 0.4mCi/$20{\mu}l$ using an automated microinjector. Nuclear imaging, histopathological and hematological studies were performed in 10 rats in each group at 1 day, 3days, 7 days, 1 month and 3 months after the injections. Results : An infiltration of inflammatory cells and necrotic changes were noted in $^{166}Ho$ treated group at 1 week after the injection. A wedge-shaped tissue defect due to necrosis, lined with infiltrated glial cells in $^{166}Ho$ treated group and a cystic defect lined with reactive astroglial cells in $^{166}Holmium$-CHICO treated group at 3 months after the injection were observed. $^{166}Ho$ alone without chitosan leaked out and caused necrotic lesion on the cerebral surface but $^{166}Holmium$-CHICO treated group did not show this feature. As the dose of $^{166}Ho$ increased, the mortality rates were also increased. The mortality rate of the $^{166}Holmium$-CHICO group was higher than the $^{166}Ho$ treated group at a dose of 0.4mCi/$20{\mu}l$/300g. There was no detectable radioactivity due to the leakage or extravasation from the injected site of the brain on the scintigraphy performed at 1 hour, 24 hours and 48 hours after the injection. There was also no detectable activity of $^{166}Holmium$-CHICO in other organs including spleen, liver and kidney. Conclusions : $^{166}Ho$-CHICO did not leak out to the critical cortical surface of the brain from the injection site and induced radiation changes of the parenchyma around the injection site without cortical damage. The sublethal dose of $^{166}Ho$-CHICO for the normal brain in rats was determined to be 0.2mCi/$20{\mu}l$/300g.