Imaging the impact of cortical microcirculation on synaptic structure and sensory-evoked hemodynamic responses in vivo.
Imaging the impact of cortical microcirculation on synaptic structure and sensory-evoked hemodynamic responses in vivo.
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DOI：
10.1371/journal.pbio.0050119
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发表时间：
2007-05
期刊：
影响因子：
9.8
通讯作者：
Murphy TH
中科院分区：
文献类型：
--
作者：
Zhang S;Murphy TH
在体内双光子显微镜被用来形象在真实的时间树突和他们的脊椎在小鼠光血栓中风模型，减少体感皮质血流量在离散地区的皮质功能地图。这种方法使我们能够定义血流，皮质结构和功能之间的关系，以前没有实现宏观成像技术的规模。当超过0.2 mm 2皮质表面的血流被阻断时，在30 min内触发对树突的急性缺血性损伤。快速损伤并不归因于一部分血管凝块甚至渗漏（外渗）。中风边界的评估显示，在数十μm范围内，完整和受损的突触回路之间存在明显的急剧过渡，并由流动和阻塞血管之间的过渡定义。虽然树突棘通常距离小的流动血管约13 μm，但我们发现，来自平均80 μm远的血管的血流可以维持完整的树突结构（在没有流动血管的区域）。与躯体感觉皮层中活动诱发的血流动力学反应相关的内在光学信号的功能成像表明，感觉诱导的信号变化在树突受损的区域被阻断，但距离树突损伤边界约400 μm。这些结果确定了血流对局部皮质精细结构和功能的影响范围，并证明梗死周围组织在卒中后最初几小时内可以发挥功能，并定位良好，有助于卒中后恢复。大脑严重依赖于充足的能量供应，因为它消耗了我们呼吸的氧气的20%。在这里，我们确定了血流中断影响突触硬接线和大脑功能的距离范围。活体小鼠的高分辨率显微镜被用于在大脑皮层血流的靶向中断期间对大脑皮层突触（神经元之间的连接部位）进行真实的成像，从而模拟小的可存活中风。在正常情况下，突触与脑血管紧密耦合，平均只有13 μm的距离。在靶向中风期间，我们发现正常的突触结构可以通过在80 μm的更大距离处流动的血管来维持。与结构相反，脑功能对血流中断更敏感，并且仅存在于距突触结构损伤边缘400 μm处。在缺乏功能的区域中识别完整的脑结构定义了其中恢复正常血流恢复功能的脑组织。我们的研究结果定义了血流对皮质精细结构和功能的影响范围，对于理解中风的病理学和血流变化如何改变正常大脑都很重要。针对靶向中风对体感皮质单个突触影响的高分辨率结构和功能成像显示，来自周围完整组织的血流可以帮助中风后立即恢复。
In vivo two-photon microscopy was used to image in real time dendrites and their spines in a mouse photothrombotic stroke model that reduced somatosensory cortex blood flow in discrete regions of cortical functional maps. This approach allowed us to define relationships between blood flow, cortical structure, and function on scales not previously achieved with macroscopic imaging techniques. Acute ischemic damage to dendrites was triggered within 30 min when blood flow over >0.2 mm2 of cortical surface was blocked. Rapid damage was not attributed to a subset of clotted or even leaking vessels (extravasation) alone. Assessment of stroke borders revealed a remarkably sharp transition between intact and damaged synaptic circuitry that occurred over tens of μm and was defined by a transition between flowing and blocked vessels. Although dendritic spines were normally ~13 μm from small flowing vessels, we show that intact dendritic structure can be maintained (in areas without flowing vessels) by blood flow from vessels that are on average 80 μm away. Functional imaging of intrinsic optical signals associated with activity-evoked hemodynamic responses in somatosensory cortex indicated that sensory-induced changes in signal were blocked in areas with damaged dendrites, but were present ~400 μm away from the border of dendritic damage. These results define the range of influence that blood flow can have on local cortical fine structure and function, as well as to demonstrate that peri-infarct tissues can be functional within the first few hours after stroke and well positioned to aid in poststroke recovery. The brain is critically dependent on an adequate supply of energy as it consumes up to 20% of the oxygen we breathe. Here we determine the distance scale over which interruptions in blood flow affect synaptic hard wiring and brain function. High-resolution microscopy of live mice was used to image cerebral cortex synapses (the sites of connections between neurons) in real time during targeted interruptions of cortical blood flow that model small survivable strokes. Under normal conditions, synapses were tightly coupled to small brain blood vessels, on average only 13 μm away. During targeted strokes, we find that normal synaptic structure can be maintained by flowing blood vessels at a much greater distance of 80 μm. In contrast to structure, brain function was more sensitive to interruption in blood flow and was only present 400 μm from the border of synaptic structural damage. The identification of intact brain structure in regions lacking function defines brain tissue in which restoration of normal blood flow restores function. Our results define the range of influence that blood flow has on cortical fine structure and function and are important for understanding both the pathology of stroke and how changes in blood flow alter the normal brain. High-resolution structural and functional imaging of the effects of targeted strokes on individual synapses in somatosensory cortex reveals that blood flow from surrounding intact tissue can aid in the immediate post-stroke recovery.
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影响因子：
3.5
作者：
Briers, J D;Webster, S
通讯作者：
Webster, S
影响因子：
4.7
作者：
Chen, YM;Vartiainen, NE;Swanson, RA
通讯作者：
Swanson, RA
DOI：
10.1159/000091705
发表时间：
2006-01-01
期刊：
Cerebrovascular diseases (Basel, Switzerland)
影响因子：
--
作者：
Fisher, Marc
通讯作者：
Fisher, Marc
影响因子：
5.3
作者：
Hasbani, MJ;Schlief, ML;Goldberg, MP
通讯作者：
Goldberg, MP
影响因子：
8.3
作者：
BOSE, B;JONES, SC;LITTLE, JR
通讯作者：
LITTLE, JR