Ischemic stroke often elicits profound white matter lesions, which results in poor neurological outcomes and impairing the recovery in post-stroke. However, few studies have focused on white matter lesions caused by c...Ischemic stroke often elicits profound white matter lesions, which results in poor neurological outcomes and impairing the recovery in post-stroke. However, few studies have focused on white matter lesions caused by cerebral ischemia. The present study was aimed to investigate the effects of cornel iridoid glycoside(CIG), a main active component extracted from Cornus officinalis, on the white matter injury induced by ischemic stroke. CIG(60 and 120 mg·kg-1) were administered intragastrically 6 h after middle cerebral artery occlusion reperfusion(MCAO) surgery once a day for 7 d. A series of behavioral tests were carried out to evaluate the neurological function of MCAO rats. White matter structure was detected by luxol fast blue staining and transmission electron microscopy. Immunohistochemical staining was used to assess myelin loss, oligodendrocytes maturation and glial activation. Results showed that CIG remarkably decreased neurological deficit score, accelerated the recovery of somatosensory and motor functions, and ameliorated the memory deficit in MCAO rats. CIG alleviated white matter lesions and demyelination, increased myelin basic protein expression and the number of mature oligodendrocytes in the corpus callosum of MCAO rats. Besides, CIG inhibited the activation of microglia and astrocytes. Further data obtained by western blot analysis indicated that CIG increased the expression of brain-derived neurotrophic factor(BDNF)/p-Trk B, neuregulin-1/Erb B, and PI3 K p110α/p-Akt/p-m TOR in the corpus callosum of MCAO rats. Our findings demonstrated that CIG protected against white matter lesions induced by cerebral ischemia and the mechanisms were partially contributed to increasing BDNF and activating neuregulin-1/Erb B signaling and its downstream PI3 K/Akt/m TOR pathway in white matter.展开更多
目的:观察慢性低灌注状态下大鼠脑白质区域血管生成及血脑屏障破坏状况及其可能联系。方法:96只大鼠随机分为假手术组、缺血1周组、缺血2周组、缺血4周组各24只,缺血组大鼠结扎双侧颈总动脉构建慢性低灌注模型,假手术组不结扎。在相应...目的:观察慢性低灌注状态下大鼠脑白质区域血管生成及血脑屏障破坏状况及其可能联系。方法:96只大鼠随机分为假手术组、缺血1周组、缺血2周组、缺血4周组各24只,缺血组大鼠结扎双侧颈总动脉构建慢性低灌注模型,假手术组不结扎。在相应时间点检测各组大鼠脑白质区域微血管密度、血管内皮细胞生长因子(VEGF)m RNA表达水平及伊文思蓝(EB)静脉注射后脑组织内EB浓度。结果:各缺血组白质区域血管网密度较假手术组高(P<0.01),血管密度在缺血2周组中达高峰。各缺血组VEGF m RNA表达水平均较假手术组增高(P<0.05),缺血2周及缺血4周组的VEGF m RNA表达水平较缺血1周组降低(P<0.05)。各缺血组EB浓度均较假手术组增高(P<0.01),缺血2周及缺血4周组EB浓度较缺血1周组增高(P<0.05)。结论:慢性低灌注状态可诱导VEGF表达、促进血管生成,这种血管生成可能参与脑白质区域血脑屏障破坏机制。展开更多
文摘Ischemic stroke often elicits profound white matter lesions, which results in poor neurological outcomes and impairing the recovery in post-stroke. However, few studies have focused on white matter lesions caused by cerebral ischemia. The present study was aimed to investigate the effects of cornel iridoid glycoside(CIG), a main active component extracted from Cornus officinalis, on the white matter injury induced by ischemic stroke. CIG(60 and 120 mg·kg-1) were administered intragastrically 6 h after middle cerebral artery occlusion reperfusion(MCAO) surgery once a day for 7 d. A series of behavioral tests were carried out to evaluate the neurological function of MCAO rats. White matter structure was detected by luxol fast blue staining and transmission electron microscopy. Immunohistochemical staining was used to assess myelin loss, oligodendrocytes maturation and glial activation. Results showed that CIG remarkably decreased neurological deficit score, accelerated the recovery of somatosensory and motor functions, and ameliorated the memory deficit in MCAO rats. CIG alleviated white matter lesions and demyelination, increased myelin basic protein expression and the number of mature oligodendrocytes in the corpus callosum of MCAO rats. Besides, CIG inhibited the activation of microglia and astrocytes. Further data obtained by western blot analysis indicated that CIG increased the expression of brain-derived neurotrophic factor(BDNF)/p-Trk B, neuregulin-1/Erb B, and PI3 K p110α/p-Akt/p-m TOR in the corpus callosum of MCAO rats. Our findings demonstrated that CIG protected against white matter lesions induced by cerebral ischemia and the mechanisms were partially contributed to increasing BDNF and activating neuregulin-1/Erb B signaling and its downstream PI3 K/Akt/m TOR pathway in white matter.
文摘目的:观察慢性低灌注状态下大鼠脑白质区域血管生成及血脑屏障破坏状况及其可能联系。方法:96只大鼠随机分为假手术组、缺血1周组、缺血2周组、缺血4周组各24只,缺血组大鼠结扎双侧颈总动脉构建慢性低灌注模型,假手术组不结扎。在相应时间点检测各组大鼠脑白质区域微血管密度、血管内皮细胞生长因子(VEGF)m RNA表达水平及伊文思蓝(EB)静脉注射后脑组织内EB浓度。结果:各缺血组白质区域血管网密度较假手术组高(P<0.01),血管密度在缺血2周组中达高峰。各缺血组VEGF m RNA表达水平均较假手术组增高(P<0.05),缺血2周及缺血4周组的VEGF m RNA表达水平较缺血1周组降低(P<0.05)。各缺血组EB浓度均较假手术组增高(P<0.01),缺血2周及缺血4周组EB浓度较缺血1周组增高(P<0.05)。结论:慢性低灌注状态可诱导VEGF表达、促进血管生成,这种血管生成可能参与脑白质区域血脑屏障破坏机制。
文摘目的探讨不同程度脑白质高信号(white matter hyperintensities,WMHs)与急性缺血性卒中(acute ischemic stroke,AIS)患者静脉溶栓后转归的相关性。方法回顾性纳入2019年1月至2022年6月在莆田市第一医院接受标准剂量阿替普酶静脉溶栓治疗的AIS患者。应用Fazekas量表对MRI显示的WMHs进行评分,将患者分为无或轻度WMHs组和中重度WMHs组。比较2组患者临床基线资料以及3个月后临床转归,转归不良定义为改良Rankin量表评分>2分。应用多变量logistic回归分析确定WMHs严重程度对静脉溶栓后转归的影响。结果共纳入103例AIS患者,年龄(64.85±10.89)岁,男性66例(64.1%)。无或轻度WMHs组60例(58.3%),中重度WMHs组43例(41.7%)。不同程度WMHs组在年龄、体重指数、收缩压、基线美国国立卫生研究院卒中量表(National Institutes of Health Stroke Scale,NIHSS)评分以及高血压、吸烟、出血性转化和发病后3个月时功能转归的患者构成比差异有统计学意义(P均<0.05)。转归良好组73例(70.9%),转归不良组30例(29.1%)。2组在年龄、体重指数、基线NIHSS评分、WMHs评分以及高血压、大动脉粥样硬化性卒中和有症状颅内出血患者构成比差异有统计学意义(P均<0.05)。多变量logistic回归分析显示,在校正混杂因素后,中重度总体WMHs是AIS患者静脉溶栓后3个月时转归不良的独立危险因素(优势比3.810,95%置信区间1.298~11.124;P=0.015)。结论中重度WMHs与AIS患者静脉溶栓后3个月时转归不良相关。
