• 대한약리학회지
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• 제30권2호
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• pp.167-179
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• 1994

Recent evidence indicates that glial cells have a wide range of funtions which are critical for maintaining a balanced homeostatic environment in the central nervous system(CNS) peripheral nervous system(PNS). Morever, astrocytes are known to participate in the tissue repair and neuroimmunologic events within the CNS through many kinds of growth factors and cytokines. We investigated the effect of $TGF\;{\beta}_1$, on the growth and biochemical changes of rat glial cells in culture. The proliferative effect was determined by $^3H-thymidine$ uptake and the double immunostain with anti-cell-specific marker and anti-Bromodeoxyuridine(BrdU) antibody. To check the effect of biochemical changes we compared the amounts of glial fibrillar acidic protein(GFAP) and the activity of glutamine synthetase(GS) in astrocyte. And the amounts of myelin basic protein and the activity of 2',3'-cyclic nucleotide phosphohydrolase(CNPase) were measured in oligodendrocyte and the amounts of peripheral myelin in Schwann cell. When $TGF\;{\beta}_1$, was treated for 2 days with cultured glial cell, $TGF\;{\beta}_1$, decreased the $^3H-thymidine$ uptake and proliferation index of double immunostain of astrocytes, which indicates the inhibition of astroglial DNA synthesis, but stimulated the growth of Schwann cell. Also, $TGF\;{\beta}_1$, decrease the GS activity and increased the amounts of GFAP in astrocyte. In the case of Schwann cells the amounts of peripheral myelin was increased when treated with $TGF\;{\beta}_1$. However, $TGF\;{\beta}_1$, didn't show any effect on the proliferation and biochemical changes in oligodendrocyte. These results suggest that $TGF\;{\beta}_1$, might have a critical action in the regulation of proliferation and biochemical changes in glial cells, especially astrocyte.

• 대한감각통합치료학회지
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• 제2권1호
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• pp.21-32
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• 2004

Objective : Effect of treadmill exercise on hippocampal neural cell proliferation under normal conditions and alcohol intoxication conditions has been recently studied; however, this effect under sensory stimulation application has not clarified yet. In the present study, the effect of compression stimulation application on hippocampal neural cell proliferation in the dentate gyrus in normal and alcohol intoxicated rats was investigated. Methods : Experimental design: comparative investigation on number of 5-Bromo-2'-deoxyuridine(BrdU)B-positive cells in dentate gyrus 5 days after commencement. Setting: animal laboratory. Participants: male Sprague-Dawley rats of 3weeks old in age weighing $80{\pm}10gm$. Intervention: animals were randomly assigned into 4 groups; control-rest group(n=8), control-compression group(n=8), alcohol intoxication-rest group(n=8) and alcohol intoxication-compression group(n=8). Animals of the alcohol intoxicated groups were injected intraperitoneally with alcohol(2g/kg) twice per day for 3 days. All animals were injected BrdU(50mg/kg) intraperitoneally, and rats compression stimulation application groups were compressed using sphygmomanometer cuff times per day, for 5 days following alcohol administration. Measures: mean number of BrdU-positive cells in dentate gyrus was observed via immunohistochemistry. Results : Compression stimulation application significantly increased the number of BrdU-positive cells in the dentate gyrus. Also, treatment with alcohol for 3 days inhibited cell proliferation, and compression stimulation application alleviated alcohol-induced inhibition of new cell formation. Conclusion : These results suggest the possibility that compression stimulation application may help in improvement following alcohol-induced brain damaged.

• Nutritional Sciences
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• 제5권4호
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• pp.175-183
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• 2002

To compare the effects of various types of dietary fiber on microbial production of short-chain fatty acids (SCFA) and on colon cell proliferation which is used as an intermediate biomarker for colon carcinogenesis, groups of 10 male Sprague-Dawley rats were fed one of four fiber-supplemented diets (6% cellulose, 6% pectin, 6% polydextrose, and a mixture of 3% cellulose and 3% polydextrose) for three weeks. As a control, a fiber-free diet was fed to a separate group of 10 rats. Cell proliferation was measured by in vivo incorporation of bromodeoxyuridine into DNA in the proximal and distal colon, respectively. Luminal concentrations of SCFA were measured by gas chromatography. Dietary fiber significantly influenced microbial production of SCFA in the colon; pectin supplementation produced the highest concentrations of luminal SCFA in both the proximal and distal colon (p<0.05). The degree of individual SCFA production was characterized by a relatively higher increase in butyrate production by the pectin-supplemented diet, and in propionate production by the polydextrose-supplemented diet, resulting in alterations of the molar ratios of acetate, propionate and butyrate. There were significant differences in colon cell proliferation among the diet groups; the pectin-supplemented diet produced a significantly higher effect on cell proliferation of distal colonic epithelial cells (p＜0.05), and the polydextrose-supplemented diet produced an intermediate effect compared to the fiber-free or cellulose-supplemented diet. Increased cell proliferation was correlated to increased luminal concentrations of butyrate in the proximal colon and to increased luminal concentrations of propionate and butyrate in the distal colon (p<0.05). Therefore, these data suggest that dietary fiber may modulate colon cell proliferation by altering luminal SCFA concentrations, particularly butyrate and perhaps propionate. In addition, the present study is the first finding that has demonstrated a relative increase in colon cell proliferation due to supplementation with polydextrose, suggesting that the overuse of this artificially synthesized polysaccharide in food processing technology needs to be carefully evaluated from the public health point of view.

• Journal of Korean Neurosurgical Society
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• 제61권1호
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• pp.10-18
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• 2018

Objective : To investigates the effect of curcumin on proliferation of spinal cord neural stem/progenitor cells (SC-NSPCs) and functional outcome in a rat spinal cord injury (SCI) model. Methods : Sixty adult male Sprague-Dawley rats were randomly and blindly allocated into three groups (sham control group; curcumin treated group after SCI; vehicle treated group after SCI). Functional recovery was evaluated by the Basso, Beattie, and Bresnahan (BBB) scale during 6 weeks after SCI. The expression of SC-NSPC proliferation and astrogliosis were analyzed by nestin/Bromodeoxyuridine (BrdU) and Glial fibrillary acidic protein (GFAP) staining. The injured spinal cord was then examined histologically, including quantification of cavitation. Results : The BBB score of the SCI-curcumin group was better than that of SCI-vehicle group up to 14 days (p<0.05). The coimmunoreactivity of nestin/BrdU in the SCI-curcumin group was much higher than that of the SCI-vehicle group 1 week after surgery (p<0.05). The GFAP immunoreactivity of the SCI-curcumin group was remarkably lower than that of the SCI-vehicle group 4 weeks after surgery (p<0.05). The lesion cavity was significantly reduced in the curcumin group as compared to the control group (p<0.05). Conclusion : These results indicate that curcumin could increase the expression of SC-NSPCs, and reduce the activity of reactive astrogliosis and lesion cavity. Consequently curcumin could improve the functional recovery after SCI via SC-NSPC properties.

• The Korean Journal of Physiology and Pharmacology
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• 제16권4호
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• pp.281-285
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• 2012

A previous animal study has shown the effects of erythropoietin (EPO) and its non-erythropoietic carbamylated derivative (CEPO) on neurogenesis in the dentate gyrus. In the present study, we sought to investigate the effect of EPO on adult hippocampal neurogenesis, and to compare the ability of EPO and CEPO promoting dendrite elongation in cultured hippocampal neural progenitor cells. Two-month-old male BALB/c mice were given daily injections of EPO (5 U/g) for seven days and were sacrificed 12 hours after the final injection. Proliferation assays demonstrated that EPO treatment increased the density of bromodeoxyuridine (BrdU)-labeled cells in the subgranular zone (SGZ) compared to that in vehicle-treated controls. Functional differentiation studies using dissociated hippocampal cultures revealed that EPO treatment also increased the number of double-labeled BrdU/microtubulea-ssociated protein 2 (MAP2) neurons compared to those in vehicle-treated controls. Both EPO and CEPO treatment significantly increased the length of neurites and spine density in MAP2(+) cells. In summary, these results provide evidences that EPO and CEPO promote adult hippocampal neurogenesis and neuronal differentiation. These suggest that EPO and CEPO could be a good candidate for treating neuropsychiatric disorders such as depression and anxiety associated with neuronal atrophy and reduced hippocampal neurogenesis.

• Journal of Nutrition and Health
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• 제31권4호
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• pp.697-707
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• 1998

This study was designed to observe the effect of dietary fiber and fat on colon tumor incidence and cell proliferation. Male Sqraue Dawley rats(n=225) at 7 weeks of age, were divided into 3 groups depending on the type of fat b(beef tallow, corn oil and DHA-rich fish oil) and each group was again divided into 3 groups depending on type of fiber(fiber-free, perctin and cellulose) . The experimental diet containing dietary fat at 15%(w/w) and fiber at 6%(w/w) levels was fed for 25 weeks. At the same time, each rats was intramuscularly injected with DMH two times a week for 6 weeks to geive total dose of 180mg/kg body weight. Cell proliferation was measured by in vivo incroporation of bromodeoxyuridine (BrdU) into DNA. Fish oil decreased the tumor incidence (9.67%) compared with beef talow (33.39%) and corn oil (21.21%). Tumor incidence was decreased in all groups that fed cellulose (11.67%) compared with those of fiber-free(21.74%) and pectic(19.70%). Most of tumors was distributed at the site of the distal colon. The rats fed both fish oil and cellulose significantly decreased th enumber of tumors and tumor incidence compared to other groups. Fish oil was more effective in preventing cell prolofieration by decreasing crypt length and labeling index(LI) compared with beef tallow(p<0.05). Cell proliferation in distal colon was more developed to the upper part of the crypt compared to proximal colon. Overall tumor incidence and cell proliferation were more affected by dietary fat. But the effect of dietary fiber was different depending on type of fat in the experimental diet. These results suggest that a DHA -rich fish oil may has more decisive effect in inhibiting the cell proliferation in colon.

• The Korean Journal of Physiology and Pharmacology
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• 제22권2호
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• pp.145-153
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• 2018

The subgranular zone (SGZ) of hippocampal dentate gyrus (HDG) is a primary site of adult neurogenesis. Toll-like receptors (TLRs), are involved in neural system development of Drosophila and innate immune response of mammals. TLR2 is expressed abundantly in neurogenic niches such as adult mammalian hippocampus. It regulates adult hippocampal neurogenesis. However, the role of TLR2 in adult neurogenesis is not well studied in global or focal cerebral ischemia. Therefore, this study aimed to investigate the role of TLR2 in adult neurogenesis after photochemically induced cerebral ischemia. At 7 days after photothrombotic ischemic injury, the number of bromodeoxyuridine (BrdU)-positive cells was increased in both TLR2 knock-out (KO) mice and wild-type (WT) mice. However, the increment rate of BrdU-positive cells was lower in TLR2 KO mice compared to that in WT mice. The number of doublecortin (DCX) and neuronal nuclei (NeuN)-positive cells in HDG was decreased after photothrombotic ischemia in TLR2 KO mice compared to that in WT mice. The survival rate of cells in HDG was decreased in TLR2 KO mice compared to that in WT mice. In contrast, the number of cleaved-caspase 3 (apoptotic marker) and the number of GFAP (glia marker)/BrdU double-positive cells in TLR2 KO mice were higher than that in WT mice. These results suggest that TLR2 can promote adult neurogenesis from neural stem cell of hippocampal dentate gyrus through increasing proliferation, differentiation, and survival from neural stem cells after ischemic injury of the brain.

• Journal of Korean Neurosurgical Society
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• 제63권2호
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• pp.163-170
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• 2020

Objective : Milk fat globule-epidermal growth factor VIII (MFG-E8) may play a key role in inflammatory responses and has the potential to function as a neuroprotective agent for ameliorating brain injury in cerebral infarction. This study aimed to determine the role of MFG-E8 in brain injury in the subacute phase of cerebral ischemia in a rat model. Methods : Focal cerebral ischemia was induced in rats by occluding the middle cerebral artery with the modified intraluminal filament technique. Twenty-four hours after ischemia induction, rats were randomly assigned to two groups and treated with either recombinant human MFG-E8 or saline. Functional outcomes were assessed using the modified Neurological Severity Score (mNSS), and infarct volumes were evaluated using histology. Anti-inflammation, angiogenesis, and neurogenesis were assessed using immunohistochemistry with antibodies against ionized calcium-binding adapter molecule 1 (Iba-1), rat endothelial cell antigen-1 (RECA-1), and bromodeoxyuridine (BrdU)/doublecortin (DCX), respectively. Results : Our results showed that intravenous MFG-E8 treatment did not reduce the infarct volume; however, the mNSS test revealed that neurobehavioral deficits were significantly improved in the MFG-E8-treated group than in the vehicle group. Immunofluorescence staining revealed a significantly lower number of Iba-1-positive cells and higher number of RECA-1 in the periinfarcted brain region, and significantly higher numbers of BrdU- and DCX-positive cells in the subventricular zone in the MFG-E8-treated group than in the vehicle group. Conclusion : Our findings suggest that MFG-E8 improves neurological function by suppressing inflammation and enhancing angiogenesis and neuronal proliferation in the subacute phase of cerebral infarction.

• 한국환경성돌연변이발암원학회지
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• 제19권2호
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• pp.89-94
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• 1999

Cell proliferation and c-Jun expression pattern in liver exposed by nongenotoxic carcinogens phenobarbital (PB) and clofibrate, and genotoxic carcinogen 2-amino-3-methylimidazo [4,5-f] quinoline (IQ) were investigated to see whether differential effects of genotoxic and non-genotoxic carcinogens on the development of neoplastic foci may be related to differential effect on cell proliferation. Male F344 rats were initially given a single intraperitioneal injection of diethylnitrosamine (200 mg/kg body weight), and 2 weeks later, animals were fed diets containing 0.03% IQ or 0.5% CE or 0.05% PB or basal diet as a control for 6 weeks. All rats were subjected to the two-thirds partial hepatectomy (PH) at week 3. Sequential sacrifice of rats was performed until 8 weeks. Cell proliferation was examined by immunohistochemical staining of bromodeoxyuridine and c-Jun expression was determined by northern blotting. The increase of cell proliferation rate after PH was significant in the rats fed 0.05% IQ and continued until 8 weeks, while the increase was not significant in the rats fed phenobarbital and clofibrate compared to that in the rats fed control diet. mRNA level of c-Jun in the liver treated with IQ was about 7 fold higher than that of control and peak at 5 hours after rH. In the liver treated with CE, mRNA level of c-Jun was 3-4 fold higher than that of control and the highest level of mRNA of c-Jun was seen at 24 hours after PH. These results show that differential effects of genotoxic and non-genotoxic carcinogens on the development of neoplastic foci may be related to differential effect on cell proliferation pattern.

• International Journal of Oral Biology
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• 제33권2호
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• pp.59-64
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• 2008

This study was designed to investigate the changes in the properties of the neuronal setm cells or progenitor cells associated with age-related decline in neurogenesis of the hippocampal dentate gyrus (DG). Active whole cells cycle marker Ki67 (a marker of whole cell cycle)-positive and S phase marker bromodeoxyuridine (BrdU)-positive. Neural stem cells gradually were reduced in the hippocampal subgranular zone (SGZ) in an age-dependant manner after birth (from P1 month to P1 year). The ratio of BrdUpositivecells/Ki67-positive cells was gradually enhanced in an age-dependent manner. The ratio of Ki67-positive cells/accu-mulating BrdU-positive cells at 3 hrs after BrdU injection was injected once a day for consecutive 5 days gradually decreased during ageing. TUNEL- and caspase 3 (apoptotic terminal caspase)-positive cells gradually decreased in the dentate SGZ during ageing and immunohistochemical findings of glial fibrillary acid protein (GFAP) were not changed during ageing. NeuN, a marker of mature neural cells, and BrdU-double positive cells gradually decreased in an age-dependent manner but differentiating ratio and survival rate of cells were not changed at 4 wks after BrdU injection once a day for consecutive 5 days. The number of BrdU-positive cells migrated from the hippocampal SGZ into granular layer and its migration speed was gradually declined during ageing. These results suggest that the adult neurogenesis in the mouse hippocampal DG gradually decrease through reducing proliferation of neural stem cells accompanying with cells cycle change and reduced cells migration rather than changes of differentiation.