Cortical Selective Neuronal Loss, Impaired Behavior, and Normal Magnetic Resonance Imaging in a New Rat Model of True Transient Ischemic Attacks
Cortical Selective Neuronal Loss, Impaired Behavior, and Normal Magnetic Resonance Imaging in a New Rat Model of True Transient Ischemic Attacks
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DOI：
10.1161/strokeaha.114.007581
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发表时间：
2015-04-01
期刊：
影响因子：
8.3
通讯作者：
Baron, Jean-Claude
中科院分区：
文献类型：
--
作者：
Ejaz, Sohail;Emmrich, Julius V.;Baron, Jean-Claude
背景和目的-新定义的短暂性脑缺血发作（TIA）是常见的，但难以诊断，因为磁共振成像（MRI）阴性的定义。然而，隐藏的潜在细胞损伤可能存在，并解释了TIA后报告的长期认知障碍。大多数先前的真正TIA的啮齿动物模型靶向纹状体或尚未完全表征。在这里，我们提出的MRI，行为和定量细胞的变化特征的一个新的啮齿动物模型，真正的TIA针对更多的behaviorally relevant cerebral cortex.Methods-Fifteen-minute远端大脑中动脉闭塞进行了29自发性高血压大鼠允许生存7至60天。行为进行了连续评估，使用全球神经和精细感觉运动测试。在再灌注后20分钟和7至60天后再次获得弥散和T2加权MRI，然后使用免疫组织化学在大脑中动脉区域定量神经元和小胶质细胞的变化。结果-在任何时间点均未观察到MRI变化或泛坏死，但斑片状皮质选择性神经元丢失影响28/29只大鼠，无论存活间隔如何，以及随时间逐渐下降的地形一致的小胶质细胞活化。神经评分没有变化，但有明显的对侧感觉运动障碍，在第28天仍在恢复。结论-我们的新啮齿动物模型模仿真正的皮质TIA的特点是正常的MRI，但一致的皮质选择性神经元丢失和小胶质细胞激活和长期的感觉运动缺陷。通过引起选择性神经元损失，TIA和沉默的微栓子可能会影响神经元储备，从而增加长期认知障碍的风险。选择性神经元丢失和小胶质细胞激活可能代表了新的治疗靶点，可以在TIA后使用适当的成像示踪剂在体内检测。
Background and Purpose-New-definition transient ischemic attacks (TIAs) are frequent but difficult to diagnose because magnetic resonance imaging (MRI)-negative by definition. However, hidden underlying cell damage might be present and account for the reported long-lasting cognitive impairment after TIAs. Most prior rodent models of true TIA targeted the striatum or have not been fully characterized. Here we present the MRI, behavioral, and quantitative cell changes characterizing a new rodent model of true TIA targeting the more behaviorally relevant cerebral cortex.Methods-Fifteen-minute distal middle cerebral artery occlusion was performed in 29 spontaneously hypertensive rats allowed to survive for 7 to 60 days. Behavior was assessed serially using both global neurological and fine sensorimotor tests. Diffusion-and T2-weighted MRI was obtained 20 min postreperfusion and again 7 to 60 days later, and then changes in neurons and microglia were quantified across the middle cerebral artery territory using immunohistochemistry.Results-No MRI changes or pan-necrosis were observed at any time point, but patchy cortical selective neuronal loss affected 28/29 rats, regardless of survival interval, together with topographically congruent microglial activation that gradually declined over time. The Neuroscore was unchanged, but there was marked contralateral sensorimotor impairment, still recovering by day 28.Conclusions-Our new rodent model mimicking true cortical TIA is characterized by normal MRI, but consistent cortical selective neuronal loss and microglial activation and long-lasting sensorimotor deficits. By causing selective neuronal loss, TIAs and silent microemboli might affect neuronal reserve, thereby increasing long-term cognitive impairment risk. Selective neuronal loss and microglial activation might represent novel therapeutic targets that could be detectable in vivo after TIAs using appropriate imaging tracers.