• Title/Summary/Keyword: brain ischemia

Search Result 403, Processing Time 0.026 seconds

The underlying mechanism of calcium toxicity-induced autophagic cell death and lysosomal degradation in early stage of cerebral ischemia

  • Jirakhamon Sengking;Pasuk Mahakkanukrauh
    • Anatomy and Cell Biology
    • /
    • v.57 no.2
    • /
    • pp.155-162
    • /
    • 2024
  • Cerebral ischemia is the important cause of worldwide disability and mortality, that is one of the obstruction of blood vessels supplying to the brain. In early stage, glutamate excitotoxicity and high level of intracellular calcium (Ca2+) are the major processes which can promote many downstream signaling involving in neuronal death and brain tissue damaging. Moreover, autophagy, the reusing of damaged cell organelles, is affected in early ischemia. Under ischemic conditions, autophagy plays an important role to maintain energy of the brain and its function. In the other hand, over intracellular Ca2+ accumulation triggers excessive autophagic process and lysosomal degradation leading to autophagic process impairment which finally induce neuronal death. This article reviews the association between intracellular Ca2+ and autophagic process in acute stage of ischemic stroke.

Pharmacological Action of New Wonbang Woohwangchungsimwon Pill on Cerebral Ischemia and Central Nervous System (신원방우황청심원의 뇌허혈 및 중추신경계에 미치는 영향)

  • 조태순;이선미;이은방;조성익;김용기;신대희;박대규
    • YAKHAK HOEJI
    • /
    • v.43 no.2
    • /
    • pp.251-262
    • /
    • 1999
  • In order to investigate pharmacological properties of New Wonbang Woohwangchungsimwon Pill (NSCH) and Wonbang Woohwangchungsimwon Pill (SCH), the effects of NSCH and SCH on cerebral ischemia and central nervous system were compared. Cerebral ischemia insult was performed using unilateral carotid artery occlusion in mongolian gerbils. The histological observations showed preventive effects of NSCH and SCH treatments with ischemia-induced brain damage. The ATP in brain tissue was decreased in vehicle-treated ischemic gerbils. This decrease was prevented by SCH treatment. In contrast to what was inhibited by NSCH and SCH treatments. While NSCH and SCH had no effects on the hexobarbital-induced sleeping time, they prevented the seizures induced by electric shock and strychnine. NSCH and SCH showed sedative effect in rotarod and spontaneous activity test. Furthermore, NSCH and SCH showed anti-stress effect. Our findings suggest that the pharmacological profiles of NSCH on cerebral ischemia and central nervous system are similar to those of SCH.

  • PDF

Effect of PAF Antagonists on the Alterations in Cerebral Hemodynamics in Transient Cerebral Ischemia (PAF 길항제가 일과성 뇌허혈에 의한 뇌혈류역학 변동에 미치는 효과)

  • 이원석;고수연
    • Biomolecules & Therapeutics
    • /
    • v.7 no.3
    • /
    • pp.234-241
    • /
    • 1999
  • The present study assessed the cerebroprotective effect of platelet-activating factor(PAF) antagonists in transient cerebral ischemia of rats. Right middle cerebral artery (MCA) of Sprague-Dawley rats was occluded for 2 hours using an intraluminal filament technique, and was reperfused for 6 hours following cerebral ischemia. The infarct area of seven coronal brain slices was measured morphometrically following stain ing in the 2% 2,3,5-triphenyltetrazolium chloride solution. The changes in regional cerebral blood flow (rCBF) and pial arteriolar diameter were measured by laser-Doppler flowmetry and by a videomicroscopy, respectively. The infarct size was significantly reduced by PAF antagonists, BN 52021 and CV-6209, which were administered i.p. 10 min before MCA occlusion. Pretreatment with PAF antagonists significantly restored the changes in pial arterial diameter as well as those in rCBF during the period of cerebral ischemia-reperfusion. PAF antagonists significantly inhibited the inducible nitric oxide synthase activity in the pial arteries ipsilateral to ischemia. These results suggest that PAF antagonists exert a cerebroprotective effect against ischemic brain damage through an improvement of postocclusive cerebral blood flow.

  • PDF

Large Scale Gene Expression Analysis in Rat Models of 4-Vessel Occlusion Ischemia (4-Vessel Occlusion 허혈동물모델에서의 대규모 유전자 발현 연구)

  • Kang, Bong-Joo;Hong, Seong-Gil;Kim, Yun-Taik;Kim, Young-Ok;Cho, Dong-Wuk
    • Korean Journal of Oriental Medicine
    • /
    • v.6 no.1
    • /
    • pp.89-98
    • /
    • 2000
  • Cerebral ischemia, the most prevalent form of clinical stroke, is a medical problem of the first magnitude. Substantial efforts are being made to develop drugs which will protect the brain from the neurodegeneration followed by an ischemic stroke. A key factor in this process is the development of animal models that mimic the neuropathological consequences of stroke. Recently, there is increasing an evidence that free radical is involved in the mechanisms of ischemic brain damage. We investigated the macro scale gene expression analysis on the global ischemia induced by 4-vessel occlusion in Wister rats. The recent availability of microarrays provides an attractive strategy for elaborating an unbiased molecular profile of large number of genes during ischemic injury. This experimental approach offers the potential to identify molecules or cellular pathways not previously associated with ischemia. Ischemia was induced by 4-vessel occlusion for 10 minutes and reperfused again. RNA from sham control brain and time-dependent ischemed brain were hybridized to microarrays containing 4,000 rat genes. 589 genes were found to be at least 2 fold regulated at one or more time points. These survey data provide the foundation studies that should provide convincing proof for ischemia and oxidative stress on gene expression.

  • PDF

Protective effects of Scutellariae Radix on impairments in learning and memory induced by brain ischemia in rats (뇌허혈로 인한 흰쥐에서의 기억력 및 학습효과 저해에 대한 황금의 보호효과)

  • Kim, Young-Ock;Lee, Se-Na;Kim, Myung-Gyou;Boo, Yung-Min;Kim, Sun-Yeou;Kim, Ho-Cheol;Leem, Kang-Hyun
    • The Korea Journal of Herbology
    • /
    • v.21 no.4
    • /
    • pp.189-195
    • /
    • 2006
  • Objectives : It has been reported previously that the roots of Scutellaria baicalensis (known as Huang-Gum in Korean, henceforth referred to as S. baicalensis) could prevent neuronal cell death after global cerebral ischemia. In Genuine Korean medicine, S. baicalensis is known to relieve fever in upper body, and it was thus thought to be able to alleviate deteriorations in brain function. Methods : The protective effects of S. baicalensis against post-stroke memory retardation using 4-vessel occlusion model were examined in the present study. Results : S. baicalensis was shown to significantly alleviate the deficits in learning and memory by increasing the fraction of time spent in the quadrant in which the platform was initially placed ($34.9\;{\pm}\;3.2%$, p < 0.05) compared to that of the ischemia group ($28.0\;{\pm}\;2.5%$). The cytoprotective effect of S. baicalensis on CA1 hippocampal neurons was evaluated by measuring the neuronal cell density. Neuronal cell density in S. baicalensis extracts-treated ischemia group ($138.0\;{\pm}\;13.6\;cells/mm^2$) was significantly increased compared to saline-treated ischemia group ($22.1 \;{\pm}\;9.3\;cells/mm^2$, p < 0.05). In the study of OX-42 immunohistochemistry, S. baicalensis could decrease the micrgial activation in hippocampus after brain ischemia. Conclusion : These results may provide experimental support for the use of S. baicalensis in treating post-stroke memory impairment.

  • PDF

Effects of Kangwhalyupung-tang on the Cerebral Neuronal Damage induced by Ischemia (강활유풍탕(羌活愈風湯)이 뇌허혈(腦虛血)로 유도된 대뇌신경세포손상(大腦神經細胞損傷)에 미치는 영향)

  • Mun Beong-Sun;Hwang Chung-Yeon;Kim Keong-Yo;Lee Geon-Mok;Sung Kang-Keong;Lee Dae-Yong;Lee Seoung-Geun
    • The Journal of Internal Korean Medicine
    • /
    • v.24 no.1
    • /
    • pp.11-20
    • /
    • 2003
  • Objective : Experimental studies have been done to elucidate the effect of kangwhalyupung-tang(KWYPT) on neuronal cell damage induced by brain ischemia. Method : The cytotoxic effect of ischemia was measured in the MTS assay cultures. MTS assay, INT assay, neurofilament(NF) enzymeimmuno assay(EIA). And the KWYPT on ischemia-induced neurotoxicity were examined by in vitro assays. Results : 1. The KWYPT protected effectively neuronal cell-death resulted from brain ischemia induced by the treatment of $95%N_2/5%CO_2$ for 10 min in those dependent fashion. 2. The KWYPT effectively increased the amount of NF resulting from brain ischemia, induced by the treatment of $95%N_2/5%CO_2$ for 15 min in those dependent fashions. Conclusions : KWYPT protects the brain ischemia-induced neurotoxicity through the increase of cell viability and of neurofilament in dose-dependent manner.

  • PDF

Anti-apoptotic and Neuroprotective Effects of Gastrodiae Elata Pharmacupuncture at $GB_{20}$ on Focal Brain Ischemic Injury Induced by Intraluminal Filament Insertion in Rats (풍지(風池)($GB_{20}$)의 천마약침(天麻藥鍼)이 Intraluminal Filament 삽입술에 의하여 유발된 백서(白鼠)의 뇌허혈에 미치는 영향)

  • Na, Geon-Ho;Youn, Dae-Hwan;Na, Chang-Su;Chae, Woo-Suk
    • Journal of Acupuncture Research
    • /
    • v.25 no.1
    • /
    • pp.1-14
    • /
    • 2008
  • Objectives : Delayed neuronal death(DND) of pyramidal neuronsin the CA1 regions of the hippocampus has been extensively studied following global brain ischemia, whereas little is known about DND in this highly vulnerable brain region after focal brain ischemia. The aim of the present study was to investigate the effect of Gastrodiae Elata(GA) pharmacopuncture on hippocampal neuronal apoptosis in rats with focal brain ischemic injury. Materials and methods : The neuroprotective effects of water extracts of GA were investigated in middle cerebral artery occlusion(MCAo) of Sprague-Dawley(SD) rats. Seventy-five healthy SD ratswere randomly divided into five groups following MCAo : control group with focal ischemia, saline injection group, pharmacopuncture group GA-1($0.0007mg/m{\ell}/g$), pharmacopuncture group GA-2($0.00035mg/m{\ell}/g$), pharmacopuncture group GA-3($0.00014mg/m{\ell}/g$). Results : The intensity of mGluR5 increased in the GA-1 group. The intensity of Bax and the Bax/Bcl-2 ratio decreased in the GA-1 group. The intensity of Bcl-2 increased in all the GA groups. The density of neurons stained by Cresyl violet and ChAT increased in the GA-1 group. Conclusions : Our study suggests that GA pharmacopuncture at $GB_{20}$ showed anti-apoptotic and neuroprotective effects on cholinergic neuronsin focal cerebral ischemia caused by stroke in SD rats.

  • PDF

The Effect of Therapeutic Exercise on Brain-Derived Neurotrophic Factor After Global Brain Ischemia in Rats (흰쥐의 전뇌허혈 후 재관류 시 운동치료에 의한 신경영양성인자 발현)

  • Gu, Sang-Hun;Song, Ju-Young;Kown, Young-Shil;Nam, Ki-Won;Song, Ju-Min;Lee, Yun-Seob;Choi, Jin-Ho;Kim, Jin-Sang
    • The Journal of Korean Physical Therapy
    • /
    • v.13 no.2
    • /
    • pp.281-292
    • /
    • 2001
  • This study was performed to investigate the effect of therapeutic exercise on brain-derived neurotrophic factor manifestation after global brain ischemia in rats. Nine rats with global ischemia were divided at random into two group. In the control group, three rats remained in cage. But, in the end, two rats were alive. In the therapeutic exercise group, six rats remained. The five rats of this group was swam for 30 minutes everyday for a week. The brain-derived neurotrophic factor expression was identified from immunohistochemistry. The results of this study were as follows : 1. In the control group, a little expression of brain-derived neurotrophic factor was observed at cortex and hippocampus layer, but cell body and axon was observed obscurely. 2. In the experimental group, a much expression of brain-derived neurotrophic factor was observed at cortex and hippocampus layer, and cell body and axon was observed clearly. In the neurological examination(beam-walking test). experimental group was obtained higher 1.4 points than control group. BDNF expression was increased by swimming for 30 minutes everyday for a week. Therefore, therapeutic exercise contribute to brain plasticity after brain ischemia.

  • PDF

Effects of Talmyung-san on the Cultured Rat Myocardiac Cell and Vascular Smooth Muscle Cell (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))

  • Seong, Gang-Gyeong;Bag, Se-Hong
    • The Journal of Internal Korean Medicine
    • /
    • v.21 no.1
    • /
    • pp.46-54
    • /
    • 2000
  • 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.

  • PDF

Effect of BHT-C extract on the infarction in cerebral ischemic rats (BHT-C의 허혈성 뇌졸중 동물에서의 뇌부종 억제효과)

  • Kim, Sung-Yoon;Park, Yong-Ki
    • The Journal of Dong Guk Oriental Medicine
    • /
    • v.11
    • /
    • pp.58-65
    • /
    • 2008
  • Objectives : BHT has been commonly used to treatment of brain disorders in Oriental clinic in Korea. The purpose of this study was to determine the inhibitory effect of modified BHT-C extract on the transient forcal cerebral ischemia in rats. Method : We prepared ischemic rats by the transient middle cerebral artery occlution(MCAO; 90 min occlusion and 144 h reperfusion) in rat brains. BHT-C extract (100 and 200 mg/kg, i.p.) was administered every day after the onset of MCAO until 6 day. Result : BHT-C extract increased survival rate of ischemic rats compared with vehicle-treated rats. BHT-C extract treated rats (100 and 200 mg/kg) were shown a significant reduction in infarct volume compared with vehicle-treated rats. Conclusions : These results suggest that BHT-C extract may contribute to its protective effects in brain ischemia through the reduction of brain infarction.

  • PDF