Rapid morphologic plasticity of peri-infarct dendritic spines after focal ischemic stroke
Rapid morphologic plasticity of peri-infarct dendritic spines after focal ischemic stroke
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DOI：
10.1161/strokeaha.107.498238
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发表时间：
2008-04-01
期刊：
影响因子：
8.3
通讯作者：
Murphy, Timothy H.
中科院分区：
文献类型：
--
作者：
Brown, Craig E.;Wong, Charles;Murphy, Timothy H.
背景和目的：局灶性脑卒中与细胞死亡、异常突触活动和神经功能损害有关.鉴于这些神经病理过程中的许多可归因于损伤后不久发生的事件，有必要了解中风如何影响存活的脑梗死区域的神经元结构，特别是在树突棘水平，其传递正常和潜在异常和损伤性突触信号。最近，我们描述了缺血诱导的第1层树突状簇的结构的变化，转基因小鼠表达YFP在第5层皮层神经元。然而，这些在体内成像实验不能解决缺血相关的现象，发生在更深的皮质结构/层，其他皮质区域，或亚微米的变化，树突棘structure.Methods -局灶性中风引起的前肢感觉运动皮层的光血栓形成的方法。中风后2，6和24小时，大脑进行处理的高尔基-考克斯染色，允许一个详细的分析初级顶端树突棘结构从层2/ 3和5皮质锥体neurons.Results -光血栓性中风引起的神经元的迅速恶化，揭示了高尔基-考克斯标记，在梗死核心，可以很容易地区分从幸存的神经元-梗死区。对> 15000个树突棘的分析显示，尽管在中风后的前24小时内，脑梗死皮层中的许多棘丢失（大约丢失38%），但保留的棘明显更长（在6小时时大约为25%）。此外，这些影响被发现在2/ 3层和5层的神经元，并主要局限于脑梗死区域（< 200 μ m的梗死边界）。结论-这些快速变化的树突棘的数量和长度可能反映了早期适应性反应的潜在脆弱的脑梗死神经元应付缺血后扩散性抑郁样去极化和突触前接触的损失。
Background and Purpose - Focal stroke is associated with cell death, abnormal synaptic activity, and neurologic impairments. Given that many of these neuropathologic processes can be attributed to events that occur shortly after injury, it is necessary to understand how stroke affects the structure of neurons in surviving peri- infarct regions, particularly at the level of the dendritic spines, which transmit normal and potentially abnormal and injurious synaptic signaling. Recently, we described ischemia- induced changes in the structure of layer 1 dendritic tufts of transgenic mice expressing YFP in layer 5 cortical neurons. However, these in vivo imaging experiments could not address ischemia- related phenomena that occur in deeper cortical structures/ layers, other cortical regions, or submicron changes in dendritic spine structure.Methods - Focal stroke was induced in the forelimb sensorimotor cortex by the photothrombotic method. Two, 6, and 24 hours after stroke, brains were processed for Golgi- Cox staining to permit a detailed analysis of primary apical dendritic spine structure from layer 2/ 3 and 5 cortical pyramidal neurons.Results - Photothrombotic stroke caused a rapid deterioration of neurons, as revealed by Golgi- Cox labeling, in the infarct core that could be readily distinguished from surviving peri- infarct regions. Analysis of > 15 000 dendritic spines revealed that although many spines were lost in the peri- infarct cortex during the first 24 hours after stroke ( approximate to 38% lost), spines that remained were significantly longer ( approximate to 25% at 6 hours). Furthermore, these effects were found in both layer 2/ 3 and 5 neurons and were restricted primarily to peri- infarct regions ( < 200 mu m from the infarct border).Conclusions - These rapid changes in dendritic spine number and length may reflect an early adaptive response of potentially vulnerable peri- infarct neurons coping with postischemic spreading depression- like depolarizations and the loss of presynaptic contacts.