• Journal of Periodontal and Implant Science
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• v.37 no.3
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• pp.553-562
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• 2007

Osteoblasts regulate osteoclastogenesis by production of various cytokines. Aggregatibacter(A) ac-tinomycetemcomitans is one of periodontopathogens which invades gingival tissue. Therefore, clarifying the effect of alive A. actinomycetemcomitans on osteoblasts is important to understand the mechanism of alveolar bone resorption in periodontitis. We investigated induction of osteoclastogenesis-inducing cytokines, adherence, and invasion by A. actinomycetemcomitans in osteoblasts. Osteoblasts were isolated from mouse calvaria and expression of cytokines was determined by RT-PCR. When the ratio of the number of A. actinomycetemcomtians to the number of osteoblasts was 10:1, 50:1 and 100:1, RANKL mRNA expression was increased. A. actinomycetemcomitans also increased expression of macrophage inflammatory protein (MIP) -1${\alpha}$, interleukin (IL)-1${\beta}$, and tumor necrosis factor (TNF)-${\alpha}$. A. actinomycetemcomitans attached to and invaded osteoblasts at ratio of 1000:1. These results suggest that A. actinomycetemcomitans increases osteoclastogenesis-inducing ability of osteoblasts by stimulating the expression of RANKL, MIP-1${\alpha}$,IL-1${\beta}$, and TNF-${\alpha}$ and that invasion of A. actinomycetemcomitans provides a means by which the bacteria escape from immune system and antibiotic therapy.

• Toxicological Research
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• v.31 no.4
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• pp.347-354
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• 2015

Excess manganese (Mn) is neurotoxic. Increased manganese stores in the brain are associated with a number of behavioral problems, including motor dysfunction, memory loss and psychiatric disorders. We previously showed that the transport and neurotoxicity of manganese after intranasal instillation of the metal are altered in Hfe-deficient mice, a mouse model of the iron overload disorder hereditary hemochromatosis (HH). However, it is not fully understood whether loss of Hfe function modifies Mn neurotoxicity after ingestion. To investigate the role of Hfe in oral Mn toxicity, we exposed Hfe-knockout ($Hfe^{-/-}$) and their control wild-type ($Hfe^{+/+}$) mice to $MnCl_2$ in drinking water (5 mg/mL) for 5 weeks. Motor coordination and spatial memory capacity were determined by the rotarod test and the Barnes maze test, respectively. Brain and liver metal levels were analyzed by inductively coupled plasma mass spectrometry. Compared with the water-drinking group, mice drinking Mn significantly increased Mn concentrations in the liver and brain of both genotypes. Mn exposure decreased iron levels in the liver, but not in the brain. Neither Mn nor Hfe deficiency altered tissue concentrations of copper or zinc. The rotarod test showed that Mn exposure decreased motor skills in $Hfe^{+/+}$ mice, but not in $Hfe^{-/-}$ mice (p = 0.023). In the Barns maze test, latency to find the target hole was not altered in Mn-exposed $Hfe^{+/+}$ compared with water-drinking $Hfe^{+/+}$ mice. However, Mn-exposed $Hfe^{-/-}$ mice spent more time to find the target hole than Mn-drinking $Hfe^{+/+}$ mice (p = 0.028). These data indicate that loss of Hfe function impairs spatial memory upon Mn exposure in drinking water. Our results suggest that individuals with hemochromatosis could be more vulnerable to memory deficits induced by Mn ingestion from our environment. The pathophysiological role of HFE in manganese neurotoxicity should be carefully examined in patients with HFE-associated hemochromatosis and other iron overload disorders.

• Journal of Korean Neurosurgical Society
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• v.63 no.2
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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.

• Journal of Korean Neurosurgical Society
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• v.29 no.9
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• pp.1222-1227
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• 2000

Objective : Vascular endothelial growth factor(VEGF), an endothelial cell specific cytokine, is a potent angiogenic growth factor implicated in the tumor angiogenesis and increases vascular permeability dramatically. Peritumoral brain edema(PTBE) occurs in 40-60% of meningiomas. Many causative factors have been investigated, but the mechanism of PTBE associate with meningioma is unclear. VEGF has been implicated as one of the causative factors of PTBE. This study was designed to determine whether the extent of VEGF expression is correlated with degree of PTBE in meningiomas. Methods : Meningioma tissue samples from 40 patients(7 men and 33 women, mean age $53{\pm}13years$) who underwent surgery were examined retrospectively for the expression of VEGF immunohistochemically. The extent of PTBE was estimated by using preoperative CT or MRI as an edema index(EI). In addition to VEGF, several causative factors including tumor size, location, histologic type, microvasculature(CD31) were compared with EI. Results : Twenty-six meningiomas demonstrated PTBE, and the other 14 did not. Of the 40 patients of meningiomas, 28 were positive(17 were 1+ and 11 were 2+) for VEGF. The EI increased significantly just as VEGF was strongly expressed(p=0.006). Microvascular proliferation was also closely correlated with the extent of peritumoral brain edema(p<0.05). Conclusion : These data suggest that VEGF expression and microvascular proliferation are closely correlated with PTBE in meningioma.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.30 no.4
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• pp.308-315
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• 2004

Aim: The aim of this study was to investigate the mechanism of promoted skin wound healing in skin defects with primary cultured oral mucosal keratinocytes. Materials and methods: Thirty adult female nude mice weighing $20{\pm}2g$ were used for the experiment. Primary cultured and suspended oral mucosal keratinocytes, labeled with BrdU, were scattered onto $1.5cm{\times}1.5cm$ sized full thickness skin defects in the experimental group(N=15), and no grafts were placed the control group(N=15). They were sacrificed at 3 days, 1 week and 2 weeks after the treatment respectively. Histological examination of each wounds were performed to review the healing progress on measuring the length from the wound margin to regenerating epithelial front. The role of keratinocytes were assessed by double immunohistochemical staining with Anti-BrdU and Anti-cytokeratin AE1/3. Results: In the experimental group the wound was completely covered with regenerating epithelia in 2 weeks, but partially regenerated in the control group. The immunohistochemical studies unexpectedly reveal that most of regenerating epithelial cells were induced from marginal epithelium of the margin, not from the scattered keratinocytes. Conclusion: We could successfully confirm that graft of primary cultured oral mucosal keratinocytes promotes the regeneration of skin defects.

• The Journal of Internal Korean Medicine
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• v.19 no.2
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• pp.278-299
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• 1998

This study was aimed to evaluate the anti-stress effect of danchisoyosan on the rats stressed by immobilization. The experimental animals were immobilized in the stress box($5{\times}5{\times}20cm$) for 12 hours in a day during 3 days, and administered $500mg/5m{\ell}/g$ of Danchisoyosan extract for 14 days before stress. There were measured the change of body weight and organ weight under immobilized-stress. The norepinephrine, epinephrine, dopamine, serotonine contents were measured by HPLC method in rat brain. There were measured the GOT, GPT contents in serum and tissue lipid peroxidation in the brain, liver, spleen, adrenalgland, pancreas, testes, thymus, heart. The following results were obtained: 1. The change of organ weight was significantly lower in control than normal group. Sample group inhibited decreased weight from stress comparing to control group. 2. Lipid peroxidation in the liver was significantly higher in control than normal group. Sample group shows significant decrease comparing to control group. 3. Lipid peroxidation in the kidney was significantly higher in control than normal group. Sample group shows significant decrease comparing to control group. 4. GPT contents in serum was significantly higher in control than normal group. Sample up shows significant decrease comparing to control group. 5. Dopamine contents in the brain was significantly higher in control than normal group. Sample group shows significant decrease comparing to control group. 6. Serotonine contents in the brain was significantly higher in control than normal group. Sample group shows significant decrease comparing to control group.

• Proceedings of the Korean Society of Medical Physics Conference
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• 2002.09a
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• pp.345-351
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• 2002

The purpose of this study was to assess clinical proton MR spectroscopy (MRS) as a noninvasive method for evaluating brain tumor malignancy at 3T high field system. Using 3T MRI/MRS system, localized water-suppressed single-voxe1 technique in patients with brain tumors was employed to evaluate spectra with peaks of N-acetyl aspartate (NAA), choline-containing compounds (Cho), creatine/phosphocreatine (Cr) and lactate. On the basis of Cr, these peak areas were quantificated as a relative ratio. The variation of metabolites measurements of the designated region in 10 normal volunteers was less than 10%. Normal ranges of NAA/Cr and Cho/Cr ratios were 1.67${\pm}$018 and 1.16${\pm}$0.15, respectively. NAA/Cr ratio of all tumor tissues was significantly lower than that of the normal tissues (p=0.005), but Cho/Cr ratio of all tumor tissue was significantly higher (p=0.001). Cho/Cr ratio of high-grade gliomas was significantly higher than that of low-grade gliomas (P=0.001). Except 4 menigiomas, lactate signal was observed in all tumor cases. The present study demonstrated that the neuronal degradation or loss was observed in all tumor tissues. Higher grade of brain tumors was correlated with higher Cho/Cr ratio, indicating a significant dependence of Cho levels on malignancy of gliomas. Our results suggest that clinical proton MR spectroscopy could be useful to predict tumor malignancy.

• Journal of the Korean Society of Radiology
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• v.11 no.7
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• pp.589-595
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• 2017

This study evaluated the effect of gadolinium contrast agents on the spectrum of metabolites during $^1H-MRS$ of brain and to investigate whether the contrast agents injected before MR spectroscopy significantly affect the estimated peaks of MRS. From January to May 2017, brain MR spectroscopy was performed on 30 patients to compare the spectrum before and after contrast injection of the brain white matter tissue. As a result, the spectrum of metabolites decreased after the paramagnetic contrast agents injected. However, it was not statistically significant which indicated that the use of contrast agent did not meaningfully affect the spectrum of metabolites. In conclusion, the use of the paramagnetic contrast before the acquisition of the spectroscopy may aid voxel positioning especially when it is difficult to determine the exact location of the lesion or the contrast is low.

• Reproductive and Developmental Biology
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• v.35 no.2
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• pp.167-174
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• 2011

Acute ischemic stroke results from sudden decrease or loss of blood supply to an area of the brain, resulting in a coinciding loss of neurological function. The antioxidant action of melatonin is an important mechanism among its known effects to protective activity during ischemic/reperfusion injury. The focus of this research, therapeutic efficacy of melatonin on recovery of neurological function following long term treatment in ischemic brain injured rats. Male Sprague-Dawley rats (n=40; 8 weeks old) were divided into the control group, and MCAo groups (Vehicle, MT7 : MCAo+ melatonin injection at 7:00, MT19 : MCAo+melatonin injection at 19:00, and MT7,19 : MCAo+melatonin injection at 7:00 and 19:00). Rat body weight and neurological function were measured every week for 8 weeks. After 8 weeks, the rats were anesthetized with a mixture of zoletil (40 mg/kg) and xylazine (10 mg/kg) and sacrificed for further analysis. Tissues were then collected for RNA isolation from brain tissue. Also, brain tissues were analyzed by histological procedures. We elucidated that melatonin was not toxic in vital organs. MT7,19 was the most rapidly got back to mild symptom on test of neurological parameter. Also, exogenous melatonin induces both the down-regulation of detrimental genes, such as NOSs and the up-regulation of beneficial gene, including BDNF during long term administration after focal cerebral ischemia. Melatonin treatment reduced the loss of primary motor cortex. Therefore, we suggest that melatonin could be act as prophylactic as well as therapeutic agent for neurorehabilitative intervention.

• Biomolecules & Therapeutics
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• v.21 no.1
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• pp.21-28
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• 2013

Microglia play a role in maintaining and resolving brain tissue homeostasis. In pathological conditions, microglia release pro-inflammatory cytokines and cytotoxic factors, which aggravate the progression of neurodegenerative diseases. Autophagy pathway might be involved in the production of pro-inflammatory cytokines and cytotoxic factors in microglia, though details of the mechanism remain largely unknown. In the present study, we examined the role of the autophagy pathway in activated BV2 microglia cells. In BV2 cells, rapamycin treatment activated the formation of anti-LC3-labeled autophagosomes, whereas the ATG5 depletion using siRNA-ATG5 prevented the formation of LC3-labeled autophagosomes, indicating that BV2 cells exhibit an active classical autophagy system. When treated with LPS, BV2 cells expressed an increase of anti-LC3-labeled dots. The levels of LC3-labeled dots were not suppressed, instead tended to be enhanced, by the inhibition of the autophagy pathway with siRNA-ATG5 or wortmannin, suggesting that LPS-induced LC3-labeled dots in nature were distinct from the typical autophagosomes. The levels of LPS-induced expression of iNOS and IL6 were suppressed by treatment with rapamycin, and conversely, their expressions were enhanced by siRNA-ATG5 treatment. Moreover, the activation of the autophagy pathway using rapamycin inhibited cell death of LPS-stimulated microglia. These results suggest that although microglia possess a typical autophagy pathway, the glial cells express a non-typical autophagy pathway in response to LPS, and the activation of the autophagy pathway suppresses the expression of iNOS and IL6, and the cell death of LPS-stimulated microglia.