• Archives of Pharmacal Research
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• v.25 no.5
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• pp.697-703
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• 2002

We investigated that the role of nitric oxide (NO) on ischemic rats in brain and heart. Ischemia was induced by both common carotid arteries (CCA) occlusion for 24h following reperfusion. Then tissue samples were removed and measured NOx. In brain, NOx was increased by about 40% vs. normal and it was significantly inhibited by aminoguanidine, selective iNOS inhibitor. This result showed that NOx concentration was increased by iNOS. We investigated the role of $Ca^{2+}$ during ischemia. Nimodipine, L-type calcium channel blocker, didn't inhibit the increases of NOx concentration during ischemia. It suggested that increased NOx was due to calcium-independent NOS. MK-801, which N-methyl-D-aspartate (NMDA) receptor antagonist, didn't significantly prevent the increases of NOx. In heart, ischemia caused NOx decrease and it is inconsistent with NOx increase in brain. Aminoguanidine and nimodipine didnt affect on NOx decrease. But MK-801 more lowered NOx concentration than those of ischemia control group. It seemed that $Ca^{2+}$ influx in heart partially occurred via NMDA receptor and inhibited by NMDA receptor antagonist. The mean arterial pressure (MAP) in ischemic rats after 24h of CCA occlusion was decreased when compared to normal value, whereas the heart rates (HR) was not different between two groups. Aminoguanidine or MK801 had no effect on MAP or HR, but nimodipine reduced MAP. There was no difference the effects of aminoguanidine, nimodipine, or MK-801, on MAP and HR between normal rats and ischemic rats. In summary, ischemic model caused an increase of NOx concentration, suggesting that this may be produced via iNOS, which is calcium independent in brain. However in heart, ischemia decreased NOx concentration and NMDA receptor was partially involved. The basal MAP was decreased in ischemic rats but HR was not different from normal control, suggesting that increased NOx in brain of ischemic rat may result in the hypotension.

• Molecules and Cells
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• v.39 no.4
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• pp.337-344
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• 2016

Intravenous administration of mesenchymal stem cells (IV-MSC) protects the ischemic rat brain in a stroke model, but the molecular mechanism underlying its therapeutic effect is unclear. We compared genomic profiles using the mRNA microarray technique in a rodent stroke model. Rats were treated with $1{\times}10^6$ IV-MSC or saline (sham group) 2 h after transient middle cerebral artery occlusion (MCAo). mRNA microarray was conducted 72 h after MCAo using brain tissue from normal rats (normal group) and the sham and MSC groups. Predicted pathway analysis was performed in differentially expressed genes (DEGs), and functional tests and immunohistochemistry for inflammation-related proteins were performed. We identified 857 DEGs between the sham and normal groups, with the majority of them (88.7%) upregulated in sham group. Predicted pathway analysis revealed that cerebral ischemia activated 10 signaling pathways mainly related to inflammation and cell cycle. IV-MSC attenuated the numbers of dysregulated genes in cerebral ischemia (118 DEGs between the MSC and normal groups). In addition, a total of 218 transcripts were differentially expressed between the MSC and sham groups, and most of them (175/218 DEGs, 80.2%) were downregulated in the MSC group. IV-MSC reduced the number of Iba-$1^+$ cells in the peri-infarct area, reduced the overall infarct size, and improved functional deficits in MCAo rats. In conclusion, transcriptome analysis revealed that IV-MSC attenuated postischemic genomic alterations in the ischemic brain. Amelioration of dysregulated inflammation- and cell cycle-related gene expression in the host brain is one of the molecular mechanisms of IV-MSC therapy for cerebral ischemia.

• Journal of Pharmacopuncture
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• v.26 no.4
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• pp.327-337
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• 2023

Objectives: Epilepsy is a neurological condition characterized by repeated seizures attributable to synchronous neuronal activity in the brain. The study evaluated the effect of acetone extract of Adansonia digitata stem bark (ASBE) on seizure score, cognition, depression, and neurodegeneration as well as the level of Gamma-Aminobutyrate acid (GABA) and glutamate in Pentylenetetrazol-kindled rats. Methods: Thirty-five rats were assigned into five groups (n = 7). Groups 1-2 received normal saline and 35 mg/kg PTZ every other day. Groups 3-4 received 125 mg/kg and 250 mg/kg ASBE orally while group 5 received 5 mg/kg diazepam daily for twenty-six days. Group 3-5 received PTZ every other day, 30 mins after ASBE and diazepam. Results: The results showed that Pentylenetetrazol (PTZ) induces seizure, reduces mobility time in force swim test and decreases the normal cell number in the brain. It also significantly decreases (p < 0.05) catalase, superoxide dismutase and reduced glutathione activities compared to the ASBE pre-treated rats. Pre-treatment with ASBE reportedly decreases seizure activities significantly (p < 0.05) and increases mobility time in the force swim test. ASBE also significantly elevate (p < 0.05) the normal cell number in the hippocampus, temporal lobe, and dentate gyrus. Conclusion: ASBE reduced seizure activity and prevented depression in PTZ-treated rats. It also prevented neurodegeneration by regulating glutamate and GABA levels in the brain as well as preventing lipid peroxidation.

• Journal of the Korean Society of Food Science and Nutrition
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• v.27 no.2
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• pp.319-325
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• 1998

The purpose of this study was to investigate the effect of green tea catechin on microsomal mixed function oxidase(MFO) system of kidney and brain in streptozotocin(STZ) induced diabetic rats. Sprague-Dawley male rats weighing 140$\pm$10g were randomly assigned to one control and three STZ-diabetic groups. Diabetic groups wer classified to DM-0C(catechin 0%/kg diet), DM-0.5C (catechin 0.5%/kg diet), and DM-1.0C(catechin 1%/kg diet) according to the level of catechin supplementation. Diabetes were experimentally induced by intravenous administration of 55mg/kg body weight of STZ in citrate buffer(pH 4.3) after 4 weeks feeding of three experimental diets. Animals were sacrificed at the sixth day of diabetic state. The contents of cytochrome P450 in kidney were increased by 77, 42, 49% in DM-0C, DM-0.5C and DM-1.0C groups, respectively, than normal group. The contents of cytochrome P450 in brain were increased by 43% in DM-0C group than normal group, but those of DM-0.5C and DM-1.0C groups were similar to that of normal group. The contents of cytochrome b5 in kidney were increased by 78, 38, 49% in DM-0C, DM-0.5C and DM-1.0C groups, respectively, than normal group. Meanwhile, the contents of cytochrome b5 in brain were not significantly different among all groups. The activities of NADPH-cytochrome P450 reductase in kidney of DM-group were increased by 27% than normal group, but those of DM-0.5C and DM-1.0C groups were 13 and 15% lower than that of DM-0C group. The activities in brain were also increased by 31% in DM-0C group, but those of DM-0.5C and DM-1.0C groups were similar to than of normal group. Levels of TBARS (thiobarbituric acid reactive substance) in kidney were increased by 147, 60 and 59% in DM-0C, DM-0.5C, and DM-1.0C groups, respectively, compared with normal group, but those of DM-0.5C and DM-1.0C groups were 36, 35% lower than that of DM-0C group. Meanwhile, the levels of TBARS in brain were not significantly different among four groups. These results indicate that dietary catechins in green tea play a powerful antioxidant role in reducing the lipid peroxidation enhanced by activation of MFO system in STZ-induced diabetes.

• Advances in Traditional Medicine
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• v.8 no.4
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• pp.430-439
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• 2008

Chungpaesagan-tang (CPSGT) is most frequently used to treat ischemic brain injury in tradition Korean medicine. Clinically, cerebral ischemia is likely to be accompanied by preexisting or complicating disease. However, animal models used to examine the effects of herbal medicines on cerebral ischemia have not given this issue sufficient consideration. The present study was undertaken to determine the effects of CPSGT on focal cerebral ischemia in normal and SHR rats subjected to transient middle cerebral artery occlusion (MCAO). Animals were divided into four groups: Normal (Sprague-Dawley) rats subjected to MACO (the NC+MCAO group), normal rats subjected to MCAO and then administered CPSGT (NC + MCAO + CP), SHR rats subjected to MCAO (SHR + MCAO), and SHR rats subjected to MCAO and then administered CPSGT (SHR + MCAO + CP). MCAO was performed using the intraluminal method. CPSGT was administrated orally twice (1 and 4 h) after MCAO. All animals were sacrificed at 24 h postoperatively. Brain tissues were stained with hematoxylin & eosin, to examine the effect of CPSGT on ischemic brain tissues. In addition, changes in TNF-$\alpha$ expression in ischemic areas were examined by immunostaining. CPSGT was found to significantly reduce infarction areas in normal and SHR rats and infarction volumes in SHR rats. Similarly, CPGST markedly increased neuron numbers and sizes in all treated groups, except cell sizes in SHRs. Furthermore, CPSGT reduced TNF-$\alpha$ expression in MCAO administered SHR rats. The findings of the present study suggest that CPSGT effectively ameliorates neuron damage caused by MACO-induced cerebral ischemia, and that it has a significant neuroprotective effect after cerebral ischemia in SHR.

• Journal of Korean Medicine Rehabilitation
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• v.18 no.2
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• pp.45-60
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• 2008

Objectives : Sopung-tang(Shufeng-tang) is a famous herbal prescription that treated ischemic brain injury. This study was designed to evaluate the effects of Sopung-tang(Shufeng-tang) on congnition and motor function recovery after ischemic brain injury in rats. Methods : Male rats were divided into 4 groups. Those rats caused ischemic brain injury by occlusion of MCA as Longa method. Control group I was per os normal saline for 7 days after ischemic brain injury. Control group II was per os normal saline for 14 days after ischemic brain injury. Experimental group I(Ex I) was taken with Sopung-tang(Shufeng-tang) for 7 days after ischemic brain injury. Experimental group II(Ex II) was taken with Sopung-tang(Shufeng-tang) for 14 days after ischemic brain injury. The author carried out neurological, cognitive motor behavior tests and histological assessment. Neurological motor behavior tests consist of limb placement test, beam-walking test and horizontal wire test. Morris water maze test was used for cognitive motor behavior test. In the histological assessment test, TTC(2,3,5-triphenylteterazolium chloride) staining, Hematoxylin & Eosin staining and immunohistochemical staining were experimented. Results : 1. In neurological motor behavior tests, motor function recovery was significantly increased in the experimental groups as compared with control groups(p<0.05). Especially Ex II was significantly increased as compared with Ex I(p<0.05). 2. In Morris water maze test, congnitive motor function recovery was significantly increased in the experimental groups as compared with control group(p<0.05). Especially Ex II was significantly increased as compared with Ex I(p<0.05). 3. In the immunohistochemical staining for the expression of BDNF in hippocampus, more immune reaction was investigated in the experimental groups as compared with control groups. Especially most immune reaction was experimented in the EX II. Conclusions : According to the above results, Sopung-tang(Shufeng-tang) can treat on the congnition and motor function recovery after ischemic brain injury in rats. And it is effective method in expression of BDNF in hippocampus.

• Journal of Nutrition and Health
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• v.2 no.4
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• pp.113-125
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• 1969

These experiments were designed to study the influence of early protein undernutrition on growth, behaviors toward food, general attitude toward a new environment, brain size and body composition of the experimental rats. The following experimental groups were studied. Lactation period (3 weeks) (Diets of mother rats) 25% Casein diet 12% Casein diet 25% Casein diet 25% Casein diet 12% Casein diet 12% Casein diet After-weaning protein deprivation period None deprivation (25% Casein diet) None deprivation (25% Casein diet) 5% Casein diet (4 weeks) 5% Casein diet (8 weeks) 5% Casein diet (4 weeks) 5% Casein diet (8 weeks) After a long period of rehabilitation with 25% casein diet the following results were obtained. 1. Growth rate during lactation period is closely related with the protein levels of the diet for mother rats. The average body weight of offsprings of the mother rat fed 25% casein diet is 46.0 grams at 21 days old. However, that of the mother rat fed 12% casein diet is only 25.0 grams. 2. The group of protein undernutrition during lactation (S weeks) (offsprings of mother rat fed low protein diet, 12% casein diet) could never catch up with the normal group in its growth even after twenty-four (24) weeks of rehabilitation. 3. However, the groups of protein undernutrition during either four (4) or even eight (8) weeks after weaning could catch up with the normal group in their growth after long period of rehabilitation. 4. The absolute amounts of carcass protein and fat of the normal group are larger than those of the protein deficient groups. In terms of percent carcass, however, the normal group showed higher body fat and lower body protein than the early deficient groups. However, there is no difference between preweaning (3 weeks) and postweaning (8 weeks) deficient groups. It is assumed, from these differences in body composition, that there might be any differences in physiological and metabolic functions among these various groups, and also that the basic formation of various metabolic regulators (protein-nature) might be fixed mostly during lactation and postweaning period. 5. The groups of protein undernutrition during either three (3) weeks lactation or four (4) weeks after weaning are not so remarkably different from the normal group in their amounts of food intake and spillage. However, the groups of undernutrition during either eight (8) weeks postweaning or eleven (11) weeks (3 weeks lactation period plus 8 weeks postweaning period) showed higher amounts of food intake and spillage. In these respects, it seems that desire for food is closely related with the degree of early hunger in protein and also seems that the longer be deficient in early life the more food spillage is found. 6. Both preweaning and postweaning deficient groups showed generally nervous and restless. The normal group is staid and showed less mobilities. 7. The average size of the brains of the group subjected to protein deficiency during three (3) weeks lactation period is smaller than that of the group of the eight (8) weeks postweaning deficiency. This means that the development of the brain is made mostly during lactation period. The group of the eleven (11) weeks postnatal deficiency is significantly different from the normal group in its brain development. It is assumed, in connection with the results of various maze tests reported, that the brain size is closely related with the intellectual ability.

• Food Quality and Culture
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• v.3 no.1
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• pp.45-48
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• 2009

The investigation assessed the influence of Compositae plants consumption on the protein profile in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in Sprague-Dawley rats by injection of STZ (45 mg/kg body weight) into tail vein. The rats were randomly assigned to five groups: normal and STZ-control fed an AIN-93 diet, and groups whose diets were supplemented with 10% Compositae powder containing Artemisia iwayomogi (A. iwayomogi), Atractylodes lancea (A. lancea) or Taraxacum mongolicum (T. mongolicum). To observe the effects of Compositae plants in the animal model, the levels of protein in liver, kidney, lung, pancreas, and brain were determined after 4 weeks. The level of protein in kidney increased significantly in rats receiving the A. iwayomogi- and T. mongolicum-supplemented diet compared to the STZ-control group. The level of protein in lung was increased significantly in the A. iwayomogi-supplemented group. Blood glucose level correlated well with brain protein level but did not correlate with other protein levels. Also, blood glucose correlated inversely with kidney, lung and brain protein levels. It is suggested that supplementation with A. iwayomogi in diabetic rats leads elevates protein in kidney and lung.

• Journal of Nutrition and Health
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• v.3 no.2
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• pp.81-85
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• 1970

These experiments were designed to study the influence of protein undernutrition during lactation period(3 wks) or after-weaning period(8 wks) on growth of organs, and on brain and liver composition of the experimental rats. The following experimental groups were studied. Group No. Rats Lactation(3 wks) (Diet of mother rat) After-weaning period(8wks) Rehabilitation Period(17wks) I 8 25% Casein diet 25% Casein diet 25% Casein diet II 8 12% Casein diet 25% Casein diet 25% Casein diet III 8 25% Casein diet 5% Casein diet 25% Casein diet IV 8 12% Casein diet 5% Casein diet 25% Casein diet After the perriod of rehabilitation(17 wks) with 25% casein diet, the following results were obtained. 1. Most of the organs except the spleen could not catch up with the normal group in their weights for the group of protein undernutrition during lactation(3 wks), even after 17 weeks of rehabilitation. For the group of protein undernutrition during after-weaning period(8 wks) brain, lung, heart, spleen and pancreas could catch up with the normal group after rehabilitation. According to this result it is assumed that the growth of brain, lung, heart and pancreas might be developed mostly during lactation and that the growth of liver and kidney might be developed after-weaning period continuously. 2. For the groups of protein underuntrition during lactation period or after-weaning period the amounts of total lipid, cholesterol and phospholipid of brain were lower than those of normal group. Especially, cholesterol level was significantly lower than normal group. And there was also a significant difference in the phospholipid level of the after-weaning(8 wks) deprivation group. 3. The groups of protein undernutrition during lactation or after-weaning period(8 wks) showed lower level of liver nitrogen and higher level of liver fat. Especially, protein undernutriton during lactation gave a greater influence on the lever of liver fat.

• Toxicological Research
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• v.23 no.3
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• pp.279-287
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• 2007

Copper (Cu) is an essential trace element indispensable for brain development and function; either excess or deficiency in Cu can cause brain malfunction. While it is known that Cu and Fe homeostasis are strictly regulated in the brain, the question as to how systemic Fe status may influence brain Cu distribution was poorly understood. This study was designed to test the hypothesis that dietary Fe condition affects Cu transport into the brain, leading to an altered brain distribution of Cu. Rats were divided into 3 groups; an Fe-deficient (Fe-D) group which received an Fe-D diet ($3{\sim}5 mg$ Fe/kg), a control group that was fed with normal diet (35mg Fe/kg), and an Fe-overload group whose diet contained an Fe-O diet (20g carbonyl Fe/kg). Following a 4-week treatment, the concentration of Cu/Fe in serum, CSF (cerebrospinal fluid) and brain were determined by AAS, and the uptake rates of Cu into choroids plexus (CP), CSF, brain capillary and parenchyma were determined by an in situ brain perfusion, followed by capillary depletion. In Fe-D and Fe-O, serum Fe level decreased by 91% (p<0.01) and increased by 131% (p<0.01), respectively, in comparison to controls. Fe concentrations in all brain regions tested (frontal cortex, striatum, hippocampus, mid brain, and cerebellum) were lower than those of controls in Fe-D rats (p<0.05), but not changed in Fe-O rats. In Fe-D animals, serum and CSF Cu were not affected, while brain Cu levels in all tested regions (frontal cortex, striatum, hippocampus, mid brain, and cerebellum) were significantly increased (p<0.05). Likewise, the unidirectional transport rate constants $(K_{in})$ of Cu in CP, CSF, brain capillary and parenchyma were significantly increased (p<0.05) in the Fe-D rats. In contrast, with Fe-O, serum, CSF and brain Cu concentrations were significantly decreased as compared to controls (p<0.05). Cu transport was no significant change of Cu transport of serum in Fe-O rats. The mRNA levels of five Cu-related transporters were not affected by Fe status except DMT1 in the CP, which was increased in Fe-D and decreased in Fe-O. Our data suggest that Cu transport into brain and ensuing brain Cu levels are regulated by systemic Fe status. Fe deficiency appears to augment Cu transport by brain barriers, leading to an accumulation of Cu in brain parenchyma.