Biphasic direct current shift, haemoglobin desaturation and neurovascular uncoupling in cortical spreading depression
Biphasic direct current shift, haemoglobin desaturation and neurovascular uncoupling in cortical spreading depression
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DOI：
10.1093/brain/awp338
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发表时间：
2010-04-10
期刊：
影响因子：
14.5
通讯作者：
Brennan, Kevin C.
中科院分区：
文献类型：
--
作者：
Chang, Joshua C.;Shook, Lydia L.;Brennan, Kevin C.
皮层扩散性抑制是一种传播性去极化波，在偏头痛、中风、蛛网膜下腔出血和脑损伤中起重要作用。皮质扩散性抑制与深刻的血管变化相关，这可能是对皮质扩散性抑制事件的临床反应的重要因素。我们使用了光学固有信号成像，电生理，钾敏感电极和光谱学的组合，以调查神经血管的变化与小鼠皮层扩散性抑制。我们确定了两个不同的阶段，改变神经血管功能，一个在传播皮层扩散性抑制波和第二个更长的阶段后，波的通道。与皮层扩散性抑制波相关的直流电移位伴随着显著的动脉收缩和皮层血红蛋白的去饱和。从最初的皮层扩散性抑制波恢复后，我们观察到第二阶段的延长，负直流偏移，动脉收缩和血红蛋白去饱和，持续至少一个小时。神经血管耦合的持续中断表现为电生理活动和灌注之间的一致性丧失。细胞外钾离子浓度增加皮层扩散性抑制波，但恢复后，波的通道，保持在基线，与不同的机制，神经血管功能障碍的第一和第二阶段。这些研究结果表明，皮层扩散性抑制与神经血管功能的多相改变，包括一个新的第二直流转变伴随着动脉收缩和组织供氧减少，这是时间和机械上不同于最初传播的皮层扩散性抑制波。血管/代谢解偶联与皮质扩散性抑制可能具有重要的临床后果，并且功能障碍的不同阶段可能代表皮质扩散性抑制发生的疾病中的单独治疗靶点。
Cortical spreading depression is a propagating wave of depolarization that plays important roles in migraine, stroke, subarachnoid haemorrhage and brain injury. Cortical spreading depression is associated with profound vascular changes that may be a significant factor in the clinical response to cortical spreading depression events. We used a combination of optical intrinsic signal imaging, electro-physiology, potassium sensitive electrodes and spectroscopy to investigate neurovascular changes associated with cortical spreading depression in the mouse. We identified two distinct phases of altered neurovascular function, one during the propagating cortical spreading depression wave and a second much longer phase after passage of the wave. The direct current shift associated with the cortical spreading depression wave was accompanied by marked arterial constriction and desaturation of cortical haemoglobin. After recovery from the initial cortical spreading depression wave, we observed a second phase of prolonged, negative direct current shift, arterial constriction and haemoglobin desaturation, lasting at least an hour. Persistent disruption of neurovascular coupling was demonstrated by a loss of coherence between electro-physiological activity and perfusion. Extracellular potassium concentration increased during the cortical spreading depression wave, but recovered and remained at baseline after passage of the wave, consistent with different mechanisms underlying the first and second phases of neurovascular dysfunction. These findings indicate that cortical spreading depression is associated with a multiphasic alteration in neurovascular function, including a novel second direct current shift accompanied by arterial constriction and decrease in tissue oxygen supply, that is temporally and mechanistically distinct from the initial propagated cortical spreading depression wave. Vascular/metabolic uncoupling with cortical spreading depression may have important clinical consequences, and the different phases of dysfunction may represent separate therapeutic targets in the disorders where cortical spreading depression occurs.