피질 뇌손상 집단과 피질하 뇌손상 집단 간 비유창성 발생에 관한 비교 연구

안종복(Jong Bok Ahn) 한국언어치료학회 2012 言語治療硏究 Vol.21 No.3

High fat diet-induced brain damaging effects through autophagy-mediated senescence, inflammation and apoptosis mitigated by ginsenoside F1-enhanced mixture

Jingang Hou,Byeongmin Jeon,Jongin Baek,Yeejin Yun,Daeun Kim,Boyoon Chang,Sungyeon Kim,Sunchang Kim 고려인삼학회 2022 Journal of Ginseng Research Vol.46 No.1

Background: Herbal medicines are popular approaches to capably prevent and treat obesity and its related diseases. Excessive exposure to dietary lipids causes oxidative stress and inflammation, which possibly induces cellular senescence and contribute the damaging effects in brain. The potential roles of selective enhanced ginsenoside in regulating high fat diet (HFD)-induced brain damage remain unknown. Methods: The protection function of Ginsenoside F1-enhanced mixture (SGB121) was evaluated by in vivo and in vitro experiments. Human primary astrocytes and SH-SY5Y cells were treated with palmitic acid conjugated Bovine Serum Albumin, and the effects of SGB121 were determined by MTT and lipid uptake assays. For in vivo tests, C57BL/6J mice were fed with high fat diet for 3 months with or without SGB121 administration. Thereafter, immunohistochemistry, western blot, PCR and ELISA assays were conducted with brain tissues. Results and conclusion: SGB121 selectively suppressed HFD-induced oxidative stress and cellular senescence in brain, and reduced subsequent inflammation responses manifested by abrogated secretion of IL-6, IL-1β and TNFα via NF-kB signaling pathway. Interestingly, SGB121 protects against HFD-induced damage by improving mitophagy and endoplasmic reticulum-stress associated autophagy flux and inhibiting apoptosis. In addition, SGB121 regulates lipid uptake and accumulation by FATP4 and PPARα. SGB121 significantly abates excessively phosphorylated tau protein in the cortex and GFAP activation in corpus callosum. Together, our results suggest that SGB121 is able to favor the resistance of brain to HFD-induced damage, therefore provide explicit evidence of the potential to be a functional food.

도담탕(導痰湯)이 뇌손상(腦損傷) 및 고혈압(高血壓)에 미치는 영향(影響)

임승민,안정조,최영,김용진,유호룡,박양춘,설인찬,황치원,조현경,Lim, Seong-Min,An, Joung-Jo,Choi, Young,Kim, Yong-Jin,Yoo, Ho-Ryoung,Park, Yang-Chun,Seol, In-Chan,Hwang, Chi-Won,Cho, Hyun-Kyung 대한한방내과학회 2001 大韓韓方內科學會誌 Vol.22 No.4

Objective : This study was carried out to investigate the effects of DDT on the brain damage and hypertension. Methods : We observed the effect of Dodamtang(DDT) extract on KCN-induced coma, focal brain ischemia by MCA occlusion, cytotoxicity and protection of PC12 cells and B103 cells induced by amyloid ${\beta}$ protein(25-35). To prove the effect of DDT as a blood pressure depressant, we measured aldosterone, renin activity, catecholamine, sodium and NO density using the seperated blood plasma. Results : DDT showed a protective effect on cytotoxicity of PC12 cells and B103 cells induced by amyloid ${\beta}$ protein(25-35) in a dose dependent manner and proved the significant abridgement of brain ischemic area and edema induced by MCA occlusion, a critical decrease of neurologic deficitic grade in the fore-limbs. DDT didn't reduce the duration of KCN(1.87mg/kg iv.)-induced coma and prolonged the survival rate in the case of KCN(3.0mg/kg iv.)-induced coma by the ratio of 20%. While DDT increased the value of NO in SHR, it significantly decreased the blood pressure of SHR and the value of aldosterone& epinephrine in SHR. Conclusions : These results suggested that DDT might be usefully applied for treatment of hypertension, cerebral infarction, and brain damage.

뇌 전두엽 손상에 대한 위스콘신카드분류검사의 판별력

김희철,박영남 대한생물치료정신의학회 1998 생물치료정신의학 Vol.4 No.2

뇌의 전두엽에 손상을 입은 환자들이 다른 부위에 손상을 입은 환자들에 비해 위스콘신카드분류검사(WCST)수행 능력이 더욱 저조하다고 알려졌지만 실제 많은 연구 결과들은 전두엽 손상 환자들의 WCST 수행력에 상당한 다양성을 보인다. 본 연구는 뇌 손상환자에서 WCST가 전두엽 병변을 얼마나 잘 찾아내는지에 대한 판별력을 조사하였다. 명백한 뇌 손상의 증거가 있는 환자 33명에 대해 WCST를 시행하고 동시에 MMSEK와 한국판 웩슬러 지능검사(KWIS) 등의 신경심리검사를 시행하였다. 뇌손상의 병변은 CT나 MRI로 확인하였고 대상 환자를 병소 부위에 따라서 전두엽에 국한된 집단(전두엽군, 10명), 전두엽 이외의 부위에 국한된 집단(비전두엽군, 10명), 전두엽과 함께 기타 다른 부위에 광범위하게 나타난 집단(광범위군; 13명)으로 구분하였다. 세 집단간에 WCST 수행력과 신경인지기능을 비교하였으며 전두엽군과 비전두엽군을 판별해 주는 WCST의 가장 적절한 cutoff score를 조사하였다. 전두엽군, 비전두엽군 및 광범위군 사이에 연령, 교육 수준, MMSEK 점수, KWIS 점수 및 WCST 평가 점수 등에서 모두 유의한 차이가 없었고, 전두엽군과 비전두엽군만을 따로 비교했을 경우에도 양군 사이에 모든 평가 변인에 대해 유의한 차이가 없었다. 전두엽군과 비전두엽군을 판별해 주는 WCST의 가장 적절한 cutoff score가 보속반응에서는 40점, 보속오류에서는 38점이었다. 이경우에 전두엽 손상 환자에 대한 WCST의 진단적 민감도는 40%이고 특이도는 70%이었다. 본 연구의 결과는 WCST의 수행력이 뇌 손상 환자에서 전두엽 병변을 특이하게 확인시켜 주지 못하므로 뇌손상 환자에서 전두엽 기능을 평가하기 위해서는 WCST 이외에 다른 부수적인 검사가 필요함을 시사한다. Objectives : It is well known that patients with frontal lobe damage perform worse on the Wisconsin Card Sorting Test(WCST) than do patients with focal nonfrontal damage. However, many practical studies have found considerable variability in WCST performances across subjects with frontal lobe damage. This study was conducted to investigate WCST's discriminating power in frontal lobe damage. Methods : Neuropsychological test such as WCST, MMSEK, and KWIS were administered to 33 patients with evident brain damge. All subjects were assigned to three groups(Frontal, Nonfrontal, and Diffuse group) on the basis of lesion location determined by neuroanatomical analysis of CT and/or MRI films. The authors investigated the differences of WCST performance among three groups and estimated the sensitivity and specificity of the WCST as an index of frontal lobe damage. Results : There were no significant differences in age, level of education, scores of MMSEK, KWIS, and WCST among the three groups. When the analyses were conducted on two groups, designated as Frontal and Nonfrontal group, there were also no significant differences in all estimated variables. The best cutoff scores for discriminating Frontal from Nonfrontal cases were a Perseverative Response score of greater than 40, and a Perseverative Error score of greater than 38, as indicating frontal damage. At this cutoff scores, the sensitivity and specificity of the WCST as an index of frontal lobe damage were 40% and 70%, respectively. Conclusion : These results suggest that performance on the WCST connot specifically identify frontal lobe damage and other tests in addition to WCST is needed for evaluating the frontal love function.

Role of Signal Transducer and Activator of Transcription 6 (Stat6) in Alcohol-induced Brain Damage

Hae Jeong Park,Jong Woo Kim,Ah Rang Cho,Jin Kyung Park,Won Sub Kang,Doh Joon Yoon 대한스트레스학회 2010 스트레스硏究 Vol.18 No.3

Signal transducer and activator of transcription 6 (Stat6)는 세포의 분화, 성장의 조절에 중요한 역할을 하며, 또한 다양한 조직과 세포의 아폽토시스를 억제하는 것으로 알려져 있다. 본 연구에서 우리는 Stat6 knockout (KO) 생쥐를 이용하여 에탄올 처치에 대한 뇌에서의 Stat6의 역할을 알아보았다. 에탄올은 BALB/c wild type (WT) 생쥐와 Stat6 KO 생쥐에 20% 에탄올로서(2 g/kg) 복강 내 주입으로 처치하였다. 에탄올 처치 후, WT과 Stat6 KO 생쥐의 뇌를 적출하고, 7.4 K 마우스 cDNA microarray 분석을 실시하였다. 분석을 위하여, WT 생쥐와 Stat6 KO 생쥐에 대해 각각 에탄올을 처치한 군과 에탄올을 처치하지 않은 군 사이에 유전자 발현 양상을 비교하였다. 우리는 WT 생쥐의 뇌에서, 세포 성장관련 전사인자의 유전자 발현이 변화하는 것을 관찰할 수 있었다. 에탄올은 SRY-box containing gene 4 (Sox4)의 발현을 증가시켰으며, hairy and enhancer of split 5 (Hes5)의 발현은 감소시켰다. Stat6 KO 생쥐의 뇌에서는 세포사멸과 관련된 유전자들의 발현이 변화하는 것을 관찰할 수 있었다. 특히 에탄올은 아폽토시스 유전자인 caspase 7 (Casp7), inositol polyphosphate-5-phosphatase D (Inpp5d)와 세포 주기 조절 유전자인 Cyclin-dependent kinase inhibitor 1C (P57) (Cdkn1c)의 발현을 증가시켰다. 반면, 항아폽토시스 유전자인 myelocytomatosis oncogene (Myc)의 발현은 감소하였다. 이러한 결과는 에탄올이 뇌 손상을 유발할 수 있으며, Stat6의 결손은 아폽토시스 유발 기전을 통해 에탄올에 의한 뇌 손상을 증가시킬 수 있다는 것을 의미한다. 이러한 결과로 Stat6가 아마도 에탄올에 의한 뇌 손상에 있어서 중요한 역할을 하는 것으로 사료된다. Signal transducer and activator of transcription 6 (Stat6) modified cell differentiation and growth, and induced the resistance to apoptosis in various tissues and cells. In this study, we assessed the role of Stat6 on acute ethanol-induced intoxication in mouse brain using Stat6 knockout (KO) mouse. The acute ethanol intoxication was induced by an intraperitoneal injection of 20% ethanol (2 g/kg) in BALB/c wild type (WT), and Stat6 KO mice. After collecting the brains of WT and KO mice, we performed 7.4 K mouse cDNA microarray analysis. The expression profiles were compared between non-treated and ethanol-treated groups for WT and Stat6 KO mice respectively. In the brains of WT mice, the changes of the expressions of transcription factor genes related with cell proliferation were shown. The ethanol increased the level of SRY-box containing gene 4 (Sox4), and decreased the level of hairy and enhancer of split 5 (Hes5). In the brains of Stat6 KO mice, the acute ethanol altered the expressions of cell death-related genes. Particularly, the acute ethanol upregulated the expressions of apoptotic genes such as caspase 7 (Casp7) and inositol polyphosphate-5-phosphatase D (Inpp5d), and of cell cycle regulatory factor gene Cyclin-dependent kinase inhibitor 1C (P57) (Cdkn1c). In contrast, it downregulated the expression of the anti-apoptotic gene myelocytomatosis oncogene (Myc). These results indicated that the acute ethanol treatment induced the brain damage, and the deficiency of Stat6 elevated this brain damage via apoptotic pathway. Our study suggests that Stat6 may play a crucial role in ethanol-induced brain damage. (Korean J Str Res 2010;18:245∼253)

The Effect of Annexin A1 as a Potential New Therapeutic Target on Neuronal Damage by Activated Microglia

You, Ji-Eun,Jung, Se-Hwa,Kim, Pyung-Hwan Korean Society for Molecular and Cellular Biology 2021 Molecules and cells Vol.44 No.4

Brain disease is known to cause irrevocable and fatal loss of biological function once damaged. One of various causes of its development is damage to neuron cells caused by hyperactivated microglia, which function as immune cells in brain. Among the genes expressed in microglia stimulated by various antigens, annexin A1 (ANXA1) is expressed in the early phase of the inflammatory response and plays an important role in controlling the immune response. In this study, we assessed whether ANXA1 can be a therapeutic target gene for the initial reduction of the immune response induced by microglia to minimize neuronal damage. To address this, mouse-origin microglial cells were stimulated to mimic an immune response by lipopolysaccharide (LPS) treatment. The LPS treatment caused activation of ANXA1 gene and expression of inflammatory cytokines. To assess the biological function in microglia by the downregulation of ANXA1 gene, cells were treated with short hairpin RNA-ANXA1. Downregulated ANXA1 affected the function of mitochondria in the microglia and showed reduced neuronal damage when compared to the control group in the co-culture system. Taken together, our results showed that ANXA1 could be used as a potential therapeutic target for inflammation-related neurodegenerative diseases.

加味六味地黃湯이 腦神經細胞 損傷 및 腦虛血 病態 모델에 미치는 영향

김진형,김윤식,설인찬,김동희 대한동의생리학회,대한동의병리학회 2003 동의생리병리학회지 Vol.17 No.2

This study was investigated to prove the effect of GMYM on the brain damage. The results were as follows; 1. showed significantly inhibitory effect on LDH release by NMDA, AMPA and Kinate. 2. GMYM showed significantly inhibitory effect on LDH release by BSO and Fe2+. 3. GMYM decreased coma duration time in a infatal dose of KCN and showed 30% of survival rate in a fatal dose. 4. GMYM showed improvement of forelimb and hindlimb test after MCA occulusion in neurological examination. 5. GMYM decreased ischemic area and edema incited by the MCA blood flow block. These results indicate that GMYM can be used in the brain damage sujected to brain ischemia. Further study will be needed about the functional mechanism and etc.

Glycyrrhizin Attenuates MPTP Neurotoxicity in Mouse and MPP+- Induced Cell Death in PC12 Cells

김윤정,이정수 대한약리학회 2008 The Korean Journal of Physiology & Pharmacology Vol.12 No.2

The present study examined the inhibitory effect of licorice compounds glycyrrhizin and a metabolite 18β -glycyrrhetinic acid on the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse and on the 1-methyl-4-phenylpyridinium (MPP+)-induced cell death in differentiated PC12 cells. MPTP treatment increased the activities of total superoxide dismutase, catalase and glutathione peroxidase and the levels of malondialdehyde and carbonyls in the brain compared to control mouse brain. Co-administration of glycyrrhizin (16.8 mg/kg) attenuated the MPTP effect on the enzyme activities and formation of tissue peroxidation products. In vitro assay, licorice compounds attenuated the MPP+-induced cell death and caspase-3 activation in PC12 cells. Glycyrrhizin up to 100μM significantly attenuated the toxicity of MPP+. Meanwhile, 18β -glycyrrhetinic acid showed a maximum inhibitory effect at 10μM; beyond this concentration the inhibitory effect declined. Glycyrrhizin and 18β -glycyrrhetinic acid attenuated the hydrogen peroxide- or nitrogen species-induced cell death. Results from this study indicate that glycyrrhizin may attenuate brain tissue damage in mice treated with MPTP through inhibitory effect on oxidative tissue damage. Glycyrrhizin and 18β -glycyrrhetinic acid may reduce the MPP+ toxicity in PC12 cells by suppressing caspase-3 activation. The effect seems to be ascribed to the antioxidant effect. The present study examined the inhibitory effect of licorice compounds glycyrrhizin and a metabolite 18β -glycyrrhetinic acid on the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse and on the 1-methyl-4-phenylpyridinium (MPP+)-induced cell death in differentiated PC12 cells. MPTP treatment increased the activities of total superoxide dismutase, catalase and glutathione peroxidase and the levels of malondialdehyde and carbonyls in the brain compared to control mouse brain. Co-administration of glycyrrhizin (16.8 mg/kg) attenuated the MPTP effect on the enzyme activities and formation of tissue peroxidation products. In vitro assay, licorice compounds attenuated the MPP+-induced cell death and caspase-3 activation in PC12 cells. Glycyrrhizin up to 100μM significantly attenuated the toxicity of MPP+. Meanwhile, 18β -glycyrrhetinic acid showed a maximum inhibitory effect at 10μM; beyond this concentration the inhibitory effect declined. Glycyrrhizin and 18β -glycyrrhetinic acid attenuated the hydrogen peroxide- or nitrogen species-induced cell death. Results from this study indicate that glycyrrhizin may attenuate brain tissue damage in mice treated with MPTP through inhibitory effect on oxidative tissue damage. Glycyrrhizin and 18β -glycyrrhetinic acid may reduce the MPP+ toxicity in PC12 cells by suppressing caspase-3 activation. The effect seems to be ascribed to the antioxidant effect.

Impact of Long-Term RF-EMF on Oxidative Stress and Neuroinflammation in Aging Brains of C57BL/6 Mice

Jeong, Ye Ji,Son, Yeonghoon,Han, Na-Kyung,Choi, Hyung-Do,Pack, Jeong-Ki,Kim, Nam,Lee, Yun-Sil,Lee, Hae-June MDPI 2018 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.19 No.7

<P>The expansion of mobile phone use has raised questions regarding the possible biological effects of radiofrequency electromagnetic field (RF-EMF) exposure on oxidative stress and brain inflammation. Despite accumulative exposure of humans to radiofrequency electromagnetic fields (RF-EMFs) from mobile phones, their long-term effects on oxidative stress and neuroinflammation in the aging brain have not been studied. In the present study, middle-aged C57BL/6 mice (aged 14 months) were exposed to 1950 MHz electromagnetic fields for 8 months (specific absorption rate (SAR) 5 W/kg, 2 h/day, 5 d/week). Compared with those in the young group, levels of protein (3-nitro-tyrosine) and lipid (4-hydroxy-2-nonenal) oxidative damage markers were significantly increased in the brains of aged mice. In addition, levels of markers for DNA damage (8-hydroxy-2′-deoxyguanosine, p53, p21, γH2AX, and Bax), apoptosis (cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase 1 (PARP-1)), astrocyte (GFAP), and microglia (Iba-1) were significantly elevated in the brains of aged mice. However, long-term RF-EMF exposure did not change the levels of oxidative stress, DNA damage, apoptosis, astrocyte, or microglia markers in the aged mouse brains. Moreover, long-term RF-EMF exposure did not alter locomotor activity in aged mice. Therefore, these findings indicate that long-term exposure to RF-EMF did not influence age-induced oxidative stress or neuroinflammation in C57BL/6 mice.</P>

탈명산(奪命散)이 배양심근세포(培養心筋細胞) 및 혈관평골근세포(血管平滑筋細胞)에 미치는 영향(影響)

성강경,박세홍,Seong, Gang-Gyeong,Bag, Se-Hong 대한한방내과학회 2000 大韓韓方內科學會誌 Vol.21 No.1

Objectives : Talmyung-san(TMS) has been used for treatment of brain diseases in Chinese traditional medicine. However, little is known about the mechanism by which TMS rescues brain cells from ischemic damages. To elucidate the protective mechanisms of TMS, we execute experiments. Methods : The effects of TMS on ischemia/reperfusion-induced cytotoxicity and generation of nitric oxide(NO) are investigated in primary neonatal myocardial cells and A7rS, aortic smooth muscle cell line. Results : Ischemia/reperfusion itself induces severe myocardial cell death in vitro. However, treatment of the cells with TMS significantly reduces both ischemia/reperfusion-induced myocardial cell death and LDH release. In addition, pretreatment of TMS before reperfusion recovers the lose of beating rates alter ischemia/reperfusion. For a while, the water extract of TMS stimulates myocardial cells to produce NO in a dose dependent manner and it protects the damage of ischemia/reperfusion-induced myocardial cells. Furthermore, the protective effects of the water extract of TMS is mimicked by treatment of sodium nitroprusside, an exogenous NO donor. NG-monomethyl-L-arginine (NGMMA), a specific inhibitor of nitric oxide synthase(NOS), significantly blocks the protective effects of TMS on the cells after ischemia/reperfusion. In addition, on ischemia the water extract of TMS induce NO in A7r5 cell. Conclusions : Taken together, we suggest that the protective effects of TMS against ischemia/reperfusion-induced myocardial damages may be mediated by NO production of myocardial and vascular smooth muscle cell during ischemic condition.