At present,predicting the severity of brain injury caused by global cerebral ischemia/reperfusion injury(GCI/RI)is a clinical problem.After such an injury,clinical indicators that can directly reflect neurological dys...At present,predicting the severity of brain injury caused by global cerebral ischemia/reperfusion injury(GCI/RI)is a clinical problem.After such an injury,clinical indicators that can directly reflect neurological dysfunction are lacking.The change in hippocampal microstructure is the key to memory formation and consolidation.Diffusion tensor imaging is a highly sensitive tool for visualizing injury to hippocampal microstructure.Although hippocampal microstructure,brain-derived neurotrophic factor(BDNF),and tropomyosin-related kinase B(Trk B)levels are closely related to nerve injury and the repair process after GCI/RI,whether these indicators can reflect the severity of such hippocampal injury remains unknown.To address this issue,we established rat models of GCI/RI using the four-vessel occlusion method.Diffusion tensor imaging parameters,BDNF,and Trk B levels were correlated with modified neurological severity scores.The results revealed that after GCI/RI,while neurological function was not related to BDNF and Trk B levels,it was related to hippocampal fractional anisotropy.These findings suggest that hippocampal fractional anisotropy can reflect the severity of hippocampal injury after global GCI/RI.The study was approved by the Institutional Animal Care and Use Committee of Capital Medical University,China(approval No.AEEI-2015-139)on November 9,2015.展开更多
目的旨在建立血管性抑郁症(vascular depression,VD)的理想动物模型。方法选用SD大鼠40只,采用数字表法随机分为4组:1手术组:双侧颈总动脉结扎(ligation of bilateral common carotid arteries,LBCCA);2假手术组:同手术组处理,但不结扎;...目的旨在建立血管性抑郁症(vascular depression,VD)的理想动物模型。方法选用SD大鼠40只,采用数字表法随机分为4组:1手术组:双侧颈总动脉结扎(ligation of bilateral common carotid arteries,LBCCA);2假手术组:同手术组处理,但不结扎;3抑郁组:慢性不可预见性温和应激(chronic unpredictable mild stress,CUMS)结合孤养,不进行手术;4模型组:LBCCA叠加CUMS,结合孤养。连续观察21 d,观测大鼠体质量变化、行为学改变、脑血流量变化以及大鼠大脑基质金属蛋白酶(matrix metalloproteinases,MMPs)、脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)、酪氨酸激酶受体B(tropomyosin related kinase B,Trk B)蛋白及其mRNA表达水平的变化。结果与假手术组比较,模型组和抑郁组大鼠体质量、糖水消耗百分率、旷场试验运动距离及站立次数均明显降低(P<0.05或P<0.01),手术组及模型组大鼠脑血流量明显降低(P<0.01),手术组及模型组MMP-2及MMP-2 mRNA表达水平显著增高(P<0.01),抑郁组及模型组海马内BDNF/Trk B及BDNF/Trk B mRNA表达均明显降低(P<0.01或P<0.05)。结论 LBCCA叠加CUMS结合孤养方法较好地模拟了抑郁核心症状快感缺乏、运动和探索能下降的行为特征和神经血管单元(neurovascular unit,NVU)稳态失衡的病理机制,是较为理想的血管性抑郁模型,可用于药理实验及治疗效果机制研究。展开更多
基金supported by the Fundamental Research Funds for Central Public Welfare Research Institute of China,Nos.2015CZ-36(to HTL)and 2019CZ-7(to WZW)。
文摘At present,predicting the severity of brain injury caused by global cerebral ischemia/reperfusion injury(GCI/RI)is a clinical problem.After such an injury,clinical indicators that can directly reflect neurological dysfunction are lacking.The change in hippocampal microstructure is the key to memory formation and consolidation.Diffusion tensor imaging is a highly sensitive tool for visualizing injury to hippocampal microstructure.Although hippocampal microstructure,brain-derived neurotrophic factor(BDNF),and tropomyosin-related kinase B(Trk B)levels are closely related to nerve injury and the repair process after GCI/RI,whether these indicators can reflect the severity of such hippocampal injury remains unknown.To address this issue,we established rat models of GCI/RI using the four-vessel occlusion method.Diffusion tensor imaging parameters,BDNF,and Trk B levels were correlated with modified neurological severity scores.The results revealed that after GCI/RI,while neurological function was not related to BDNF and Trk B levels,it was related to hippocampal fractional anisotropy.These findings suggest that hippocampal fractional anisotropy can reflect the severity of hippocampal injury after global GCI/RI.The study was approved by the Institutional Animal Care and Use Committee of Capital Medical University,China(approval No.AEEI-2015-139)on November 9,2015.
