DI-3n-butyiphthalide can effectively treat cerebral ischemia; however, the mechanisms underlying the effects of dl-3n-butylphthalide on microcirculation disorders following diffuse brain injury remain unclear. In this...DI-3n-butyiphthalide can effectively treat cerebral ischemia; however, the mechanisms underlying the effects of dl-3n-butylphthalide on microcirculation disorders following diffuse brain injury remain unclear. In this study, models of diffuse brain injury were established in Sprague-Dawley rats with the vertical impact method. DI-3n-butylphthalide at 80 and 160 mg/kg was given via intraperitoneal injection immediately after diffuse brain injury. Ultrastructural changes in the cerebral cortex were observed using electron microscopy. Cerebral blood flow was measured by laser Doppler flowmetry, vascular density was marked by tannic acid-ferric chloride staining, vascular permeability was es- timated by the Evans blue method, brain water content was measured using the dry-wet method, and rat behavior was measured by motor function and sensory function tests. At 6, 24, 48, and 72 hours after administration of dl-3n-butylphthalide, reduced cerebral ultrastructure damage, in- creased vascular density and cerebral blood flow, and improved motor and sensory functions were observed. Our findings demonstrate that dl-3n-butylphthalide may have protective effects against diffuse brain injury by ameliorating microcirculation disorder and reducing blood-brain barrier dam- age and cerebral edema.展开更多
Caspase-8 plays an important role in the mediation of inflammation and the effect of its role in subarachnoid hemorrhage remains elusive.The nucleotide-binding oligomerization domain-like receptor protein 3 inflammaso...Caspase-8 plays an important role in the mediation of inflammation and the effect of its role in subarachnoid hemorrhage remains elusive.The nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome has been postulated to mediate inflammation during SAH.The aim of the present study was to investigate the effects of caspase-8 inhibition on SAH injury and further elucidate the molecular mechanisms.In this study,a subarachnoid hemorrhage model was established by endovascular perforation process in adult male Sprague-Dawley rats.Z-IETD-FMK(0.5,1,2 mg/kg;an inhibitor of caspase-8)was delivered via intravenous(tail vein)injection immediately after subarachnoid hemorrhage.After 12 hours of subarachnoid hemorrhage,western blot assay showed that the expression of cleaved caspase-8 was significantly increased at 12 hours,peaked at 24 hours,and then decreased at 72 hours after subarachnoid hemorrhage.Immunofluorescence staining demonstrated that caspase-8 was expressed in microglia after subarachnoid hemorrhage.Z-IETDFMK significantly improved neurological deficits and reduced brain water content 24 hours after subarachnoid hemorrhage.The Morris water maze and rotarod test confirmed that Z-IETD-FMK significantly improved spatial learning and memory abilities and motor coordination at 21–27 days after subarachnoid hemorrhage.Furthermore,inhibition of caspase-8 activation reduced the expression of pyrin domain-containing 3,caspase-1,and interleukin-1βafter subarachnoid hemorrhage.In conclusion,our findings suggest that caspase-8 inhibition alleviates subarachnoid hemorrhage-induced brain injuries by suppressing inflammation.The study was approved by the Institutional Animal Ethics Committee of the First Affiliated Hospital,School of Medicine,Zhejiang University,China(approval No.2016-193)on February 25,2016.展开更多
采用一套专门设计的由微创光纤探头组成的光纤光谱仪生物组织光学参数测试系统,对颅脑创伤的大鼠创伤侧和对照侧进行近红外光谱检测及脑水含量(brain water content:BWC)测定。通过采用Feeney's自由落体撞击法建立大鼠急性局灶性脑...采用一套专门设计的由微创光纤探头组成的光纤光谱仪生物组织光学参数测试系统,对颅脑创伤的大鼠创伤侧和对照侧进行近红外光谱检测及脑水含量(brain water content:BWC)测定。通过采用Feeney's自由落体撞击法建立大鼠急性局灶性脑挫裂伤模型,以近红外光谱技术和干湿比重法监测伤后脑水肿的变化。实验发现:伤后1h,伤侧脑组织已发生水肿,伤后24～72h,伤侧脑水肿达高峰,随后逐渐下降;用脱水剂后,脑水肿情况逐渐好转,随着药物失效,水肿又一次发生。生物组织优化散射系数(Reduced Scat-tering Coefficient:μ′s)与BWC的变化规律一致,有很好的线性相关性,能够较好的反映脑组织水肿程度以及药物脱水效果。证实近红外光谱技术用于颅脑创伤实时监测的可行性,为颅脑创伤的研究提出了一种新技术。展开更多
目的探讨复苏后缺血缺氧性脑病大鼠脑组织含水量(BWC)与水通道蛋白-4(aquaporin-4,AQP4)表达水平的动态变化及其相关性。方法建立大鼠窒息心肺复苏模型,干湿质量法测定自主循环恢复后1、3和6 h BWC的变化;同时,利用半定量免疫组织化学...目的探讨复苏后缺血缺氧性脑病大鼠脑组织含水量(BWC)与水通道蛋白-4(aquaporin-4,AQP4)表达水平的动态变化及其相关性。方法建立大鼠窒息心肺复苏模型,干湿质量法测定自主循环恢复后1、3和6 h BWC的变化;同时,利用半定量免疫组织化学的方法检测脑组织AQP4表达水平的变化;分析两者的相关性。结果大鼠复苏后,随时间的延长BWC明显增加。各时间点BWC与对照组相比均有显著性差异(P值均<0.05)。其中,复苏组大鼠6 h BWC明显高于1、3 h;而1、3 h大鼠的BWC无明显差异。同时,复苏后脑组织AQP4水平的表达,也呈现出与BWC变化几乎相同的趋势。相关分析表明,BWC与脑组织AQP4呈明显正相关(r=0.791,P<0.01)。结论复苏后早期大鼠已出现明显的脑水肿,且与脑组织AQP4表达水平正相关,提示AQP4可能参与复苏后早期脑水肿的形成过程。展开更多
基金supported by the grants from Hebei Province Science and Technology Ministry,No.20276102DKey Project of Hebei Province Education Ministry,No.ZD2010106
文摘DI-3n-butyiphthalide can effectively treat cerebral ischemia; however, the mechanisms underlying the effects of dl-3n-butylphthalide on microcirculation disorders following diffuse brain injury remain unclear. In this study, models of diffuse brain injury were established in Sprague-Dawley rats with the vertical impact method. DI-3n-butylphthalide at 80 and 160 mg/kg was given via intraperitoneal injection immediately after diffuse brain injury. Ultrastructural changes in the cerebral cortex were observed using electron microscopy. Cerebral blood flow was measured by laser Doppler flowmetry, vascular density was marked by tannic acid-ferric chloride staining, vascular permeability was es- timated by the Evans blue method, brain water content was measured using the dry-wet method, and rat behavior was measured by motor function and sensory function tests. At 6, 24, 48, and 72 hours after administration of dl-3n-butylphthalide, reduced cerebral ultrastructure damage, in- creased vascular density and cerebral blood flow, and improved motor and sensory functions were observed. Our findings demonstrate that dl-3n-butylphthalide may have protective effects against diffuse brain injury by ameliorating microcirculation disorder and reducing blood-brain barrier dam- age and cerebral edema.
基金supported by Clinical Scientific Foundation of Zhejiang Medical Association of China,No.2018ZYC-A09(to HL)
文摘Caspase-8 plays an important role in the mediation of inflammation and the effect of its role in subarachnoid hemorrhage remains elusive.The nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome has been postulated to mediate inflammation during SAH.The aim of the present study was to investigate the effects of caspase-8 inhibition on SAH injury and further elucidate the molecular mechanisms.In this study,a subarachnoid hemorrhage model was established by endovascular perforation process in adult male Sprague-Dawley rats.Z-IETD-FMK(0.5,1,2 mg/kg;an inhibitor of caspase-8)was delivered via intravenous(tail vein)injection immediately after subarachnoid hemorrhage.After 12 hours of subarachnoid hemorrhage,western blot assay showed that the expression of cleaved caspase-8 was significantly increased at 12 hours,peaked at 24 hours,and then decreased at 72 hours after subarachnoid hemorrhage.Immunofluorescence staining demonstrated that caspase-8 was expressed in microglia after subarachnoid hemorrhage.Z-IETDFMK significantly improved neurological deficits and reduced brain water content 24 hours after subarachnoid hemorrhage.The Morris water maze and rotarod test confirmed that Z-IETD-FMK significantly improved spatial learning and memory abilities and motor coordination at 21–27 days after subarachnoid hemorrhage.Furthermore,inhibition of caspase-8 activation reduced the expression of pyrin domain-containing 3,caspase-1,and interleukin-1βafter subarachnoid hemorrhage.In conclusion,our findings suggest that caspase-8 inhibition alleviates subarachnoid hemorrhage-induced brain injuries by suppressing inflammation.The study was approved by the Institutional Animal Ethics Committee of the First Affiliated Hospital,School of Medicine,Zhejiang University,China(approval No.2016-193)on February 25,2016.
文摘采用一套专门设计的由微创光纤探头组成的光纤光谱仪生物组织光学参数测试系统,对颅脑创伤的大鼠创伤侧和对照侧进行近红外光谱检测及脑水含量(brain water content:BWC)测定。通过采用Feeney's自由落体撞击法建立大鼠急性局灶性脑挫裂伤模型,以近红外光谱技术和干湿比重法监测伤后脑水肿的变化。实验发现:伤后1h,伤侧脑组织已发生水肿,伤后24～72h,伤侧脑水肿达高峰,随后逐渐下降;用脱水剂后,脑水肿情况逐渐好转,随着药物失效,水肿又一次发生。生物组织优化散射系数(Reduced Scat-tering Coefficient:μ′s)与BWC的变化规律一致,有很好的线性相关性,能够较好的反映脑组织水肿程度以及药物脱水效果。证实近红外光谱技术用于颅脑创伤实时监测的可行性,为颅脑创伤的研究提出了一种新技术。
文摘目的探讨复苏后缺血缺氧性脑病大鼠脑组织含水量(BWC)与水通道蛋白-4(aquaporin-4,AQP4)表达水平的动态变化及其相关性。方法建立大鼠窒息心肺复苏模型,干湿质量法测定自主循环恢复后1、3和6 h BWC的变化;同时,利用半定量免疫组织化学的方法检测脑组织AQP4表达水平的变化;分析两者的相关性。结果大鼠复苏后,随时间的延长BWC明显增加。各时间点BWC与对照组相比均有显著性差异(P值均<0.05)。其中,复苏组大鼠6 h BWC明显高于1、3 h;而1、3 h大鼠的BWC无明显差异。同时,复苏后脑组织AQP4水平的表达,也呈现出与BWC变化几乎相同的趋势。相关分析表明,BWC与脑组织AQP4呈明显正相关(r=0.791,P<0.01)。结论复苏后早期大鼠已出现明显的脑水肿,且与脑组织AQP4表达水平正相关,提示AQP4可能参与复苏后早期脑水肿的形成过程。
