基于多光谱光学内源信号成像的皮层扩散性抑制过程多参数监测
|
摘要
皮层扩散性抑制(Cortical spreading depression, CSD)作为偏头痛、脑缺血以及脑外伤等多种神经性疾病的病理学模型,对其在体发展特性的研究和了解,特别是对其引起的血液动力学响应和能量代谢变化的研究可以帮助人们更好的研究和治疗这些神经性疾病。多光谱光学内源信号(Optical intrinsic signal, OIS)成像技术不仅具有较高的时间和空间分辨率,并且通过一定的数据分析处理后还可以提供多参数信息(血液动力学、线粒体代谢以及光散射)。因此,我们利用多光谱光学内源信号成像技术来实现对活体动物(大鼠和小鼠)CSD发展过程的多参数监测。主要研究内容如下：
(1)首先介绍了多光谱OIS成像系统,并推导了多光谱OIS的基本数据分析模型——修正的朗伯比尔定律,针对以前多光谱OIS数据分析过程中相关因素考虑不全面的问题,分析了一系列与脑组织光吸收有关的生色团(血红蛋白,水,细胞色素c,细胞色素氧化酶,NADH和FAD),给出了这些生色团可见光范围内的吸收光谱,并确定其是否参与多光谱OIS的数据分析,从而最终推导出多光谱OIS的数据分析公式,为准确分析CSD相关的多光谱OIS提供方法学基础。我们还模拟和分析了数据分析模型中的重要参数——差分路径因子,定性的给出了差分路径因子随组织吸收、散射特性改变所产生的变化特征,并估计了脑组织的吸收和散射等光学特性,最后给出了可见光范围内(450-650nm)差分路径因子随波长的变化曲线。
(2)采用多光谱OIS成像同时监测了大鼠CSD过程中多生理参数的变化,包括氧合血红蛋白(Oxygen-hemoglobin, HbO)、脱氧血红蛋白(Deoxygen-hemoglobin，HbR)、细胞色素c、细胞色素氧化酶、FAD以及光散射。发现CSD过程中450,470,500,530,550,570nm OIS显示出四相变化,而600,630和650nm OIS表现出复杂的两相变化。而在CSD过程中,HbO显示出显著的上升;HbR则出现下降、上升、下降的三相变化；光散射显示了先增强后减弱的变化特征；细胞色素c和细胞色素氧化酶先是被还原接着又被氧化；而FAD下降然后恢复至基线值。其中HbR的上升,细胞色素c和细胞色素氧化酶的还原说明了大鼠CSD过程中氧的供应曾一度存在不足。发现在多光谱数据拟合过程中如果不考虑其它生色团(FAD,细胞色素c和细胞色素氧化酶)和散射的变化,得到的血红蛋白浓度变化(HbO和HbR)很可能不准确。并且CSD过程中细胞色素c的变化和550nm OIS紧密相关；细胞色素氧化酶的变化和450,600,650nm OIS紧密相关；而FAD的变化和450,470nm OIS紧密相关。所以在使用这些波长的OIS计算血红蛋白变化时,应当考虑这些生色团的影响,从而避免HbO和HbR计算的不准确。
(3)采用多光谱光学内源信号成像系统研究了小鼠CSD的时变特性。30分钟内在小鼠脑皮层分别诱发两次CSD,发现这两次CSD显示出不同特性：450,470,500,530,550和570nm OIS在第一次CSD中显示出三相变化,最后幅值高于基线水平,而在第二次CSD中为四相变化；600,630和650nm OIS在第一次CSD中具有四相变化,并且最后幅值保持在低于基线值水平,600nm OIS在第二次CSD中仍具有四相变化,而630和650nm OIS在第二次CSD中只有三相变化,并且最后都能恢复到本次CSD发生之前的基线水平；HbO和总血红蛋白(Total hemoglobin, HbT)在第一次CSD中是下降的,但在第二次CSD中是上升的；光散射在第一次CSD中先上升然后下降最后长时间缓慢下降,但在第二次CSD中只有上升和恢复的变化；脑皮层大动脉管径在第一次CSD中有三相变化：剧烈收缩,恢复以及缓慢收缩,在第二次CSD中有四相变化：小舒张,收缩,大舒张以及恢复。而两次CSD中还原态细胞色素c和细胞色素氧化酶的上升以及FAD的下降都说明线粒体是处于还原状态,脑组织是处于缺氧的状态,只是第一次CSD的缺氧状况相较于第二次CSD更为严重。另外,第一次CSD会引起脑皮层很长时间的严重缺血,表现为HbT一直缓慢地下降,动脉血管也缓慢而长时间地收缩。
(4)研究了小鼠单侧颈总动脉结扎缺血后诱发的连续两次CSD的发展特性,以及双侧颈总动脉结扎缺血后小鼠自发CSD的发展特性。发现单侧缺血小鼠第一次CSD各生理参数的变化大体上和未缺血情况类似,只是持续时间明显变长,而还原态细胞色素c和细胞色素氧化酶响应幅度变大；单侧缺血小鼠第二次CSD多数生理参数的变化大体上也和未缺血情况类似,只有HbO显示出不一致,未缺血情况下Hb0是急剧上升的,而缺血状态下HbO有一个初始的小下降,然后小幅上升。小鼠双侧颈总动脉结扎缺血后自发CSD的多光谱OIS表现为所有波长统一的光强上升,而这种上升是由于散射增强而导致的。
Cortical spreading depression (CSD) has been an important disease model of neural disorders, such as migraine, cerebral ischemia and trauma et.al, characterization of CSD in vivo, especially in the related hemodynamics and energy metabolism, could help us with the therapy of these neural disorders. Multi-spectral optical intrinsic signal (OIS) imaging is an in vivo imaging technique with high temporal and spatial resolution, and could offer multi-parameter changes (hemodynamics, mitochondrial metabolism and light scattering) by using proper data analyzing method. Thus, we use multi-spectral OIS imaging to simultaneously investigate changes in multi-parameter during CSD in vivo (in rats and mice). The main contents of our study are listed as following:
(1) Firstly we introduced the Multi-spectral OIS imaging system. Then the modified Lambert-Beer law was derived. In most previous studies, OIS was employed to only characterize changes of hemoglobin during CSD in vivo by ignoring other related factors. To solve this problem, we analyzed a series of chromophores (hemoglobin, water, cytochrome c, cytochrome oxidase, NADH and FAD) which related to tissue absorption, and determined whether they will be included in the data analysis model through their absorption spectra. We offered the final data analysis equation of multi-spectral OIS, and established the data analysis model. Moreover, we simulated one important parameter of the data analysis model-the differential pathlength, and showed that the differential pathlength depends on the tissue optical properties. So we estimated the absorption and scattering properties of brain tissue, and then showed the differential pathlength as a function of wavelengths between450run and650nm.
(2) Multi-spectral OIS imaging was used to simultaneously investigate changes in multi-parameter during CSD in rats, including:oxygen-hemoglobin (HbO), deoxygen-hemoglobin (HbR), cytochrome c, cytochrome oxidase, FAD and light scattering. The OIS responses at450,470,500,530,550and570nm showed a similar four-phasic pattern during CSD, while responses at600,630and650nm had a complex biphasic pattern. HbO showed a strong increase; HbR indicated decreased, increased and decreased triphasic change; light scattering showed a biphasic change that was characterized by a initial increase followed by a decrease; cytochrome c and cytochrome oxidase were strongly reduced at first and later shifted toward an oxidized state; FAD decreased and slowly recovered to baseline. The increase in HbR and reduction in cytochrome c and cytochrome oxidase suggested that the supply of oxygen was not sufficient once during CSD in rats. We showed that the hemodynamic changes during CSD may not be correctly estimated if the scattering and other chromophores (FAD, cytochrome c and cytochrome oxidase) are not included in the fitting model of multi-spectra data analysis. Cytochrome c was related to OIS at550nm; cytochrome oxidase was related to OIS at450,600and650nm; and FAD was related to OIS at450and470nm during CSD. Therefore, if utilizing OIS at these wavelengths to determine the hemoglobin changes during CSD, the corresponding chromophores should be taken into account to avoid inaccurate results.
(3) Multi-spectral OIS imaging was used to investigate time-varying CSD in mice. Two CSD were induced respectively in30minutes in mice, and these two CSD indicated different responses:450,470,500,530,550and570nm OIS showed triphasic changes during1st CSD and was higher than baseline at last, while showed four-phasic pattern during2nd CSD;600,630and650nm OIS showed four-phasic changes during1st CSD and was lower than baseline at last, while600nm OIS was still with four-phasic changes during2nd CSD,630and650nm OIS indicated triphasic changes during2nd CSD; HbO and total hemoglobin (HbT) decreased in1st CSD but increased in2nd CSD; light scattering increased initially, then decreased and at last slowly decreased prolonged in1st CSD, but increased and recovered in2nd CSD; the pial arteries showed triphasic changes in1st CSD:constricted, then recovered and at last mildly constricted for a long time, but indicated four-phasic changes during2nd CSD:small dilation, constriction, large dilation and recovery. The increase of reduced cytochrome c and cytochrome oxidase and the decrease of FAD suggested that mitochondrial metabolism was in reduced state and hypoxia happened in brain tissue in both two CSD, but the hypoxia in1st CSD was severer than in2nd CSD. Moreover, the1st CSD could induce prolong ischemia in the mouse's cortex, characterized by the prolong decrease of HbT and constriction of arteries.
(4) We investigated two induced consecutive CSD in ischemic mice with right common carotid artery occlusion (CCAO), and observed the spontaneous CSD in ischemic mice with bilateral CCAO by using multi-spectral OIS imaging. We found that changes in all parameters were similar during1st CSD between ischemic mice and normal mice, expect the duration of changes was longer and the amplitude of reduced cytochrome c and cytochrome oxidase was larger in ischemic mice; that changes in all parameters during2nd CSD between ischemic mice and normal mice were also similar expect HbO, HbO strongly increased in normal mice while initially decreased and then mildly increased in ischemic mice. The spontaneous CSD in ischemic mice with bilateral CCAO showed identical increase in all wavelengths of multi-spectral OIS imaging, and this increase in OIS was caused by the increase in light scattering.
(1)首先介绍了多光谱OIS成像系统,并推导了多光谱OIS的基本数据分析模型——修正的朗伯比尔定律,针对以前多光谱OIS数据分析过程中相关因素考虑不全面的问题,分析了一系列与脑组织光吸收有关的生色团(血红蛋白,水,细胞色素c,细胞色素氧化酶,NADH和FAD),给出了这些生色团可见光范围内的吸收光谱,并确定其是否参与多光谱OIS的数据分析,从而最终推导出多光谱OIS的数据分析公式,为准确分析CSD相关的多光谱OIS提供方法学基础。我们还模拟和分析了数据分析模型中的重要参数——差分路径因子,定性的给出了差分路径因子随组织吸收、散射特性改变所产生的变化特征,并估计了脑组织的吸收和散射等光学特性,最后给出了可见光范围内(450-650nm)差分路径因子随波长的变化曲线。
(2)采用多光谱OIS成像同时监测了大鼠CSD过程中多生理参数的变化,包括氧合血红蛋白(Oxygen-hemoglobin, HbO)、脱氧血红蛋白(Deoxygen-hemoglobin，HbR)、细胞色素c、细胞色素氧化酶、FAD以及光散射。发现CSD过程中450,470,500,530,550,570nm OIS显示出四相变化,而600,630和650nm OIS表现出复杂的两相变化。而在CSD过程中,HbO显示出显著的上升;HbR则出现下降、上升、下降的三相变化；光散射显示了先增强后减弱的变化特征；细胞色素c和细胞色素氧化酶先是被还原接着又被氧化；而FAD下降然后恢复至基线值。其中HbR的上升,细胞色素c和细胞色素氧化酶的还原说明了大鼠CSD过程中氧的供应曾一度存在不足。发现在多光谱数据拟合过程中如果不考虑其它生色团(FAD,细胞色素c和细胞色素氧化酶)和散射的变化,得到的血红蛋白浓度变化(HbO和HbR)很可能不准确。并且CSD过程中细胞色素c的变化和550nm OIS紧密相关；细胞色素氧化酶的变化和450,600,650nm OIS紧密相关；而FAD的变化和450,470nm OIS紧密相关。所以在使用这些波长的OIS计算血红蛋白变化时,应当考虑这些生色团的影响,从而避免HbO和HbR计算的不准确。
(3)采用多光谱光学内源信号成像系统研究了小鼠CSD的时变特性。30分钟内在小鼠脑皮层分别诱发两次CSD,发现这两次CSD显示出不同特性：450,470,500,530,550和570nm OIS在第一次CSD中显示出三相变化,最后幅值高于基线水平,而在第二次CSD中为四相变化；600,630和650nm OIS在第一次CSD中具有四相变化,并且最后幅值保持在低于基线值水平,600nm OIS在第二次CSD中仍具有四相变化,而630和650nm OIS在第二次CSD中只有三相变化,并且最后都能恢复到本次CSD发生之前的基线水平；HbO和总血红蛋白(Total hemoglobin, HbT)在第一次CSD中是下降的,但在第二次CSD中是上升的；光散射在第一次CSD中先上升然后下降最后长时间缓慢下降,但在第二次CSD中只有上升和恢复的变化；脑皮层大动脉管径在第一次CSD中有三相变化：剧烈收缩,恢复以及缓慢收缩,在第二次CSD中有四相变化：小舒张,收缩,大舒张以及恢复。而两次CSD中还原态细胞色素c和细胞色素氧化酶的上升以及FAD的下降都说明线粒体是处于还原状态,脑组织是处于缺氧的状态,只是第一次CSD的缺氧状况相较于第二次CSD更为严重。另外,第一次CSD会引起脑皮层很长时间的严重缺血,表现为HbT一直缓慢地下降,动脉血管也缓慢而长时间地收缩。
(4)研究了小鼠单侧颈总动脉结扎缺血后诱发的连续两次CSD的发展特性,以及双侧颈总动脉结扎缺血后小鼠自发CSD的发展特性。发现单侧缺血小鼠第一次CSD各生理参数的变化大体上和未缺血情况类似,只是持续时间明显变长,而还原态细胞色素c和细胞色素氧化酶响应幅度变大；单侧缺血小鼠第二次CSD多数生理参数的变化大体上也和未缺血情况类似,只有HbO显示出不一致,未缺血情况下Hb0是急剧上升的,而缺血状态下HbO有一个初始的小下降,然后小幅上升。小鼠双侧颈总动脉结扎缺血后自发CSD的多光谱OIS表现为所有波长统一的光强上升,而这种上升是由于散射增强而导致的。
Cortical spreading depression (CSD) has been an important disease model of neural disorders, such as migraine, cerebral ischemia and trauma et.al, characterization of CSD in vivo, especially in the related hemodynamics and energy metabolism, could help us with the therapy of these neural disorders. Multi-spectral optical intrinsic signal (OIS) imaging is an in vivo imaging technique with high temporal and spatial resolution, and could offer multi-parameter changes (hemodynamics, mitochondrial metabolism and light scattering) by using proper data analyzing method. Thus, we use multi-spectral OIS imaging to simultaneously investigate changes in multi-parameter during CSD in vivo (in rats and mice). The main contents of our study are listed as following:
(1) Firstly we introduced the Multi-spectral OIS imaging system. Then the modified Lambert-Beer law was derived. In most previous studies, OIS was employed to only characterize changes of hemoglobin during CSD in vivo by ignoring other related factors. To solve this problem, we analyzed a series of chromophores (hemoglobin, water, cytochrome c, cytochrome oxidase, NADH and FAD) which related to tissue absorption, and determined whether they will be included in the data analysis model through their absorption spectra. We offered the final data analysis equation of multi-spectral OIS, and established the data analysis model. Moreover, we simulated one important parameter of the data analysis model-the differential pathlength, and showed that the differential pathlength depends on the tissue optical properties. So we estimated the absorption and scattering properties of brain tissue, and then showed the differential pathlength as a function of wavelengths between450run and650nm.
(2) Multi-spectral OIS imaging was used to simultaneously investigate changes in multi-parameter during CSD in rats, including:oxygen-hemoglobin (HbO), deoxygen-hemoglobin (HbR), cytochrome c, cytochrome oxidase, FAD and light scattering. The OIS responses at450,470,500,530,550and570nm showed a similar four-phasic pattern during CSD, while responses at600,630and650nm had a complex biphasic pattern. HbO showed a strong increase; HbR indicated decreased, increased and decreased triphasic change; light scattering showed a biphasic change that was characterized by a initial increase followed by a decrease; cytochrome c and cytochrome oxidase were strongly reduced at first and later shifted toward an oxidized state; FAD decreased and slowly recovered to baseline. The increase in HbR and reduction in cytochrome c and cytochrome oxidase suggested that the supply of oxygen was not sufficient once during CSD in rats. We showed that the hemodynamic changes during CSD may not be correctly estimated if the scattering and other chromophores (FAD, cytochrome c and cytochrome oxidase) are not included in the fitting model of multi-spectra data analysis. Cytochrome c was related to OIS at550nm; cytochrome oxidase was related to OIS at450,600and650nm; and FAD was related to OIS at450and470nm during CSD. Therefore, if utilizing OIS at these wavelengths to determine the hemoglobin changes during CSD, the corresponding chromophores should be taken into account to avoid inaccurate results.
(3) Multi-spectral OIS imaging was used to investigate time-varying CSD in mice. Two CSD were induced respectively in30minutes in mice, and these two CSD indicated different responses:450,470,500,530,550and570nm OIS showed triphasic changes during1st CSD and was higher than baseline at last, while showed four-phasic pattern during2nd CSD;600,630and650nm OIS showed four-phasic changes during1st CSD and was lower than baseline at last, while600nm OIS was still with four-phasic changes during2nd CSD,630and650nm OIS indicated triphasic changes during2nd CSD; HbO and total hemoglobin (HbT) decreased in1st CSD but increased in2nd CSD; light scattering increased initially, then decreased and at last slowly decreased prolonged in1st CSD, but increased and recovered in2nd CSD; the pial arteries showed triphasic changes in1st CSD:constricted, then recovered and at last mildly constricted for a long time, but indicated four-phasic changes during2nd CSD:small dilation, constriction, large dilation and recovery. The increase of reduced cytochrome c and cytochrome oxidase and the decrease of FAD suggested that mitochondrial metabolism was in reduced state and hypoxia happened in brain tissue in both two CSD, but the hypoxia in1st CSD was severer than in2nd CSD. Moreover, the1st CSD could induce prolong ischemia in the mouse's cortex, characterized by the prolong decrease of HbT and constriction of arteries.
(4) We investigated two induced consecutive CSD in ischemic mice with right common carotid artery occlusion (CCAO), and observed the spontaneous CSD in ischemic mice with bilateral CCAO by using multi-spectral OIS imaging. We found that changes in all parameters were similar during1st CSD between ischemic mice and normal mice, expect the duration of changes was longer and the amplitude of reduced cytochrome c and cytochrome oxidase was larger in ischemic mice; that changes in all parameters during2nd CSD between ischemic mice and normal mice were also similar expect HbO, HbO strongly increased in normal mice while initially decreased and then mildly increased in ischemic mice. The spontaneous CSD in ischemic mice with bilateral CCAO showed identical increase in all wavelengths of multi-spectral OIS imaging, and this increase in OIS was caused by the increase in light scattering.
引文
[1]. GG Somjen, Mechanisms of spreading depression and hypoxic spreading depression-like depolarization. Physiol Rev,2001.81(3):1065-96.
[2]. D.W. Busija, F. Bari, F. Domoki, et al., Mechanisms involved in the cerebrovascular dilator effects of cortical spreading depression. Prog Neurobiol,2008.86(4):379-95.
[3]. A.A.P. Leao, Spreading depression of activity in the cerebral cortex. J Neurophysiol, 1944.7:359-90.
[4]. J.C. Szerb, Glutamate release and spreading depression in the fascia dentata in response to microdialysis with high K+:role of glia Brain Res,1991. 542(2):259-65.
[5]. O. Herreras, GG Somjen, Analysis of potential shifts associated with recurrent spreading depression and prolonged unstable spreading depression induced by microdialysis of elevated K+ in hippocampus of anesthetized rats. Brain Res,1993. 610(2):283-94.
[6]. H. Martins-Ferreira, M. Nedergaard, C. Nicholson, Perspectives on spreading depression. Brain Res Brain Res Rev,2000.32(1):215-34.
[7]. P. Mares, N. Kriz, G. Brozek, et al., Anoxic changes of extracellular potassium concentration in the cerebral cortex of young rats. Exp Neurol,1976.53(1):12-20.
[8]. A.J. Hansen, T. Zeuthen, Extracellular ion concentrations during spreading depression and ischemia in the rat brain cortex. Acta Physiol Scand,1981. 113(4):437-45.
[9]. R.P. Kraig, C. Nicholson, Extracellular ionic variations during spreading depression. Neuroscience,1978.3(11):1045-59.
[10]. GG Somjen, P.G. Aitken, The ionic and metabolic responses associated with neuronal depression of Leao's type in cerebral cortex and in hippocampal formation. An Acad Bras Cienc,1984.56(4):495-504.
[11]. Y. Xie, E. Zacharias, P. Hoff, et al., Ion channel involvement in anoxic depolarization induced by cardiac arrest in rat brain. J Cereb Blood Flow Metab, 1995.15(4):587-94.
[12]. C. Nicholson, Comparative neurophysiology of spreading depression in the cerebellum. An Acad Bras Cienc,1984.56(4):481-94.
[13]. M. Fabricius, L.H. Jensen, M. Lauritzen, Microdialysis of interstitial amino acids during spreading depression and anoxic depolarization in rat neocortex. Brain Res, 1993.612(1-2):61-9.
[14]. A.J. Hansen, C.E. Olsen, Brain extracellular space during spreading depression and ischemia Acta Physiol Scand,1980.108(4):355-65.
[15]. J. Jing, P.G. Aitken, G.G. Somjen, Interstitial volume changes during spreading depression (SD) and SD-like hypoxic depolarization in hippocampal tissue slices. J Neurophysiol,1994.71(6):2548-51.
[16]. R.P. Kraig, C.R. Ferreira-Filho, C. Nicholson, Alkaline and acid transients in cerebellar microenvironment J Neurophysiol,1983.49(3):831-50.
[17]. C.K. Tong, M. Chesler, Endogenous pH shifts facilitate spreading depression by effect on NMD A receptors. J Neurophysiol,1999.81(4):1988-91.
[18]. Z.Q. Xiong, J.L. Stringer, Extracellular pH responses in CA1 and the dentate gyrus during electrical stimulation, seizure discharges, and spreading depression. J Neurophysiol,2000.83(6):3519-24.
[19]. G.G Somjen, Acidification of interstitial fluid in hippocampal formation caused by seizures and by spreading depression. Brain Res,1984.311(1):186-8.
[20]. M. Chesler, R.P. Kraig, Intracellular pH transients of mammalian astrocytes. J Neurosci,1989.9(6):2011-9.
[21]. M. Lauritzen, Cerebral blood flow in migraine and cortical spreading depression. Acta Neurol Scand Suppl,1987.113:1-40.
[22]. C. Yokota, Y. Kuge, Y. Hasegawa, et al., Unique profile of spreading depression in a primate model. J Cereb Blood Flow Metab,2002.22(7):835-42.
[23]. K.C. Brennan, L. Beltran-Parrazal, H.E. Lopez-Valdes, et al., Distinct vascular conduction with cortical spreading depression. J Neurophysiol,2007. 97(6):4143-51.
[24]. A. Charles, K. Brennan, Cortical spreading depression-new insights and persistent questions. Cephalalgia,2009.29(10):1115-24.
[25]. J.M. Smith, D.P. Bradley, M.F. James, et al., Physiological studies of cortical spreading depression. Biol Rev Camb Philos Soc,2006.81(4):457-81.
[26]. A. Gorji, Spreading depression:a review of the clinical relevance. Brain Res Brain Res Rev,2001.38(1-2):33-60.
[27]. M. Peeters, M.J. Gunthorpe, P.J. Strijbos, et al., Effects of pan-and subtype-selective N-methyl-D-aspartate receptor antagonists on cortical spreading depression in the rat:therapeutic potential for migraine. J Pharmacol Exp Ther, 2007.321(2):564-72.
[28]. G.C. Petzold, O. Windmuller, S. Haack, et al., Increased extracellular K+ concentration reduces the efficacy of N-methyl-D-aspartate receptor antagonists to block spreading depression-like depolarizations and spreading ischemia Stroke, 2005.36(6):1270-7.
[29]. M. Lauritzen, A.J. Hansen, The effect of glutamate receptor blockade on anoxic depolarization and cortical spreading depression. J Cereb Blood Flow Metab,1992. 12(2):223-9.
[30]. Leao AAP, M. RS, Propagation of spreading cortical depression. J Neurophysiol, 1945.8:33-45.
[31]. K. Buchheim, F. Weissinger, H. Siegmund, et al., Intrinsic optical imaging reveals regionally different manifestation of spreading depression in hippocampal and entorhinal structures in vitro. Exp Neurol,2002.175(1):76-86.
[32]. I. Vilagi, N. Klapka, H.J. Luhmann, Optical recording of spreading depression in rat neocortical slices. Brain Res,2001.898(2):288-96.
[33]. M. Nedergaard, J. Astrup, Infarct rim:effect of hyperglycemia on direct current potential and [14C]2-deoxyglucose phosphorylation. J Cereb Blood Flow Metab, 1986.6(5):607-15.
[34]. H. Otsuka, K. Ueda, A. Heimann, et al., Effects of cortical spreading depression on cortical blood flow, impedance, DC potential, and infarct size in a rat venous infarct model. Exp Neurol,2000.162(1):201-14.
[35]. L. von Baumgarten, R. Trabold, S. Thal, et al., Role of cortical spreading depressions for secondary brain damage after traumatic brain injury in mice. J Cereb Blood Flow Metab,2008.28(7):1353-60.
[36]. A. Mayevsky, A. Doron, T. Manor, et al., Cortical spreading depression recorded from the human brain using a multiparametric monitoring system. Brain Res,1996. 740(1-2):268-74.
[37]. A.J. Strong, M. Fabricius, M.G. Boutelle, et al., Spreading and synchronous depressions of cortical activity in acutely injured human brain. Stroke,2002. 33(12):2738-43.
[38]. M. Fabricius, S. Fuhr, R. Bhatia, et al., Cortical spreading depression and peri-infarct depolarization in acutely injured human cerebral cortex. Brain,2006. 129(Pt 3):778-90.
[39]. J.P. Dreier, J. Woitzik, M. Fabricius, et al., Delayed ischaemic neurological deficits after subarachnoid haemorrhage are associated with clusters of spreading depolarizations. Brain,2006.129(Pt 12):3224-37.
[40]. C. Dohmen, O.W. Sakowitz, M. Fabricius, et al., Spreading depolarizations occur in human ischemic stroke with high incidence. Ann Neurol,2008.63(6):720-8.
[41]. J.P. Dreier, S. Major, A. Manning, et al., Cortical spreading ischaemia is a novel process involved in ischaemic damage in patients with aneurysmal subarachnoid haemorrhage. Brain,2009.132(Pt 7):1866-81.
[42]. C. Iadecola, From CSD to headache:a long and winding road. Nat Med,2002. 8(2):110-2.
[43]. M. Lauritzen, J.P. Dreier, M. Fabricius, et al., Clinical relevance of cortical spreading depression in neurological disorders:migraine, malignant stroke, subarachnoid and intracranial hemorrhage, and traumatic brain injury. J Cereb Blood Flow Metab,2001.31(1):17-35.
[44]. M.F. James, J.M. Smith, S.J. Boniface, et al., Cortical spreading depression and migraine:new insights from imaging? Trends Neurosci,2001.24(5):266-71.
[45]. M. Lauritzen, Pathophysiology of the migraine aura. The spreading depression theory. Brain,1994.117(Pt 1):199-210.
[46]. M. Lauritzen, Cortical spreading depression in migraine. Cephalalgia,2001. 21(7):757-60.
[47]. K.A. Hossmann, Viability thresholds and the penumbra of focal ischemia. Ann Neurol,1994.36(4):557-65.
[48]. U. Dirnagl, C. Iadecola, M.A. Moskowitz, Pathobiology of ischaemic stroke:an integrated view. Trends Neurosci,1999.22(9):391-7.
[49]. R. Gill, P. Andine, L. Hillered, et al., The effect of MK-801 on cortical spreading depression in the penumbral zone following focal ischaemia in the rat J Cereb Blood Flow Metab,1992.12(3):371-9.
[50]. J.A. Hartings, A.J. Strong, M. Fabricius, et al., Spreading depolarizations and late secondary insults after traumatic brain injury. J Neurotrauma,2009.26(11):1857-66.
[51]. C.S. Roy, C.S. Sherrington, On the Regulation of the Blood-supply of the Brain. J Physiol,1890.11(1-2):85-15817.
[52]. D. Malonek, U. Dirnagl, U. Lindauer, et al., Vascular imprints of neuronal activity: relationships between the dynamics of cortical blood flow, oxygenation, and volume changes following sensory stimulation. Proc Natl Acad Sci U S A,1997. 94(26):14826-31.
[53]. A.K. Dunn, A. Devor, A.M. Dale, et al., Spatial extent of oxygen metabolism and hemodynamic changes during functional activation of the rat somatosensory cortex. Neuroimage,2005.27(2):279-90.
[54]. E.M. Hillman, Optical brain imaging in vivo:techniques and applications from animal to man. J Biomed Opt,2007.12(5):051402.
[55]. M.E. Raichle, Cognitive neuroscience. Bold insights. Nature,2001. 412(6843):128-30.
[56]. A. Zepeda, C. Arias, F. Sengpiel, Optical imaging of intrinsic signals:recent developments in the methodology and its applications. J Neurosci Methods,2004. 136(1):1-1.
[57]. D.K. Hill, R.D. Keynes, Opacity changes in stimulated nerve. J Physiol,1949. 108(3):278-81.
[58]. L.B. Cohen, R.D. Keynes, D. Landowne, Changes in light scattering that accompany the action potential in squid giant axons:potential-dependent components. J Physiol,1972.224(3):701-25.
[59]. R.A. Stepnoski, A. LaPorta, F. Raccuia-Behling, et al., Noninvasive detection of changes in membrane potential in cultured neurons by light scattering Proc Natl Acad Sci U S A,1991.88(21):9382-6.
[60]. B.A. MacVicar, D. Hochman, Imaging of synaptically evoked intrinsic optical signals in hippocampal slices. J Neurosci,1991.11(5):1458-69.
[61]. D. Malonek, A. Grinvald, Interactions between electrical activity and cortical microcirculation revealed by imaging spectroscopy:implications for functional brain mapping. Science,1996.272(5261):551-4.
[62]. A. Grinvald, R.D. Frostig, R.M. Siegel, et al., High-resolution optical imaging of functional brain architecture in the awake monkey. Proc Natl Acad Sci U S A,1991. 88(24):11559-63.
[63]. E. Shtoyerman, A. Arieli, H. Slovin, et al., Long-term optical imaging and spectroscopy reveal mechanisms underlying the intrinsic signal and stability of cortical maps in V1 of behaving monkeys. J Neurosci,2000.20(21):8111-21.
[64]. Y.B. Sirotin, E.M. Hillman, C. Bordier, et al., Spatiotemporal precision and hemodynamic mechanism of optical point spreads in alert primates. Proc Natl Acad Sci U S A,2009.106(43):18390-5.
[65]. B.D. Rubin, L.C. Katz, Optical imaging of odorant representations in the mammalian olfactory bulb. Neuron,1999.23(3):499-511.
[66]. L. Belluscio, L.C. Katz, Symmetry, stereotypy, and topography of odorant representations in mouse olfactory bulbs. J Neurosci,2001.21(6):2113-22.
[67]. M. Wachowiak, L.B. Cohen, Correspondence between odorant-evoked patterns of receptor neuron input and intrinsic optical signals in the mouse olfactory bulb. J Neurophysiol,2003.89(3):1623-39.
[68]. M.W. Spitzer, M.B. Calford, J.C. Clarey, et al., Spontaneous and stimulus-evoked intrinsic optical signals in primary auditory cortex of the cat. J Neurophysiol,2001. 85(3):1283-98.
[69]. N. Harel, N. Mori, S. Sawada, et al., Three distinct auditory areas of cortex (Al, All, and AAF) defined by optical imaging of intrinsic signals. Neuroimage,2000. 11(4):302-12.
[70]. A.J. Blood, N. Pouratian, A.W. Toga, Temporally staggered forelimb stimulation modulates barrel cortex optical intrinsic signal responses to whisker stimulation. J Neurophysiol,2002.88(1):422-37.
[71]. D.B. Polley, C.H. Chen-Bee, R.D. Frostig, Varying the degree of single-whisker stimulation differentially affects phases of intrinsic signals in rat barrel cortex. J Neurophysiol,1999.81(2):692-701.
[72]. M. Jones, J. Berwick, D. Johnston, et al., Concurrent optical imaging spectroscopy and laser-Doppler flowmetry:the relationship between blood flow, oxygenation, and volume in rodent barrel cortex. Neuroimage,2001.13(6 Pt 1):1002-15.
[73]. A. Devor, A.K. Dunn, M.L. Andermann, et al., Coupling of total hemoglobin concentration, oxygenation, and neural activity in rat somatosensory cortex. Neuron, 2003.39(2):353-9.
[74]. P. Gouras, Spreading depression of activity in amphibian retina Am J Physiol,1958. 195(1):28-32.
[75]. H. Martins-Ferreira, GO. de Castro, Light-scattering changes accompanying spreading depression in isolated retina J Neurophysiol,1966.29(4):715-26.
[76]. R.W. Snow, C.P. Taylor, F.E. Dudek, Electrophysiological and optical changes in slices of rat hippocampus during spreading depression. J Neurophysiol,1983. 50(3):561-72.
[77]. P.G. Aitken, GC. Tombaugh, D.A. Turner, et al., Similar propagation of SD and hypoxic SD-like depolarization in rat hippocampus recorded optically and electrically. J Neurophysiol,1998.80(3):1514-21.
[78]. M. Muller, G.G Somjen, Intrinsic optical signals in rat hippocampal slices during hypoxia-induced spreading depression-like depolarization. J Neurophysiol,1999. 82(4):1818-31.
[79]. P.G. Aitken, D. Fayuk, G.G. Somjen, et al., Use of intrinsic optical signals to monitor physiological changes in brain tissue slices. Methods,1999.18(2):91-103.
[80]. S. Bahar, D. Fayuk, G.G. Somjen, et al., Mitochondrial and intrinsic optical signals imaged during hypoxia and spreading depression in rat hippocampal slices. J Neurophysiol,2000.84(1):311-24.
[81]. R. Barer, K.F. Ross, S. Tkaczyk, Refractometry of living cells. Nature,1953. 171(4356):720-4.
[82]. Kreisman NR, LAMANNA JC, LIAO SC, et al., Light transmission as an index of cell volume in hippocampal slices:optical differences of interfaced and submerged positions. Brain Res,1995.693:179-186.
[83]. L. Tao, D. Masri, S. Hrabetova, et al., Light scattering in rat neocortical slices differs during spreading depression and ischemia. Brain Res,2002.952(2):290-300.
[84]. D. Fayuk, P.G. Aitken, G.G. Somjen, et al., Two different mechanisms underlie reversible, intrinsic optical signals in rat hippocampal slices. J Neurophysiol,2002. 87(4):1924-37.
[85]. A.S. Obeidat, R.D. Andrew, Spreading depression determines acute cellular damage in the hippocampal slice during oxygen/glucose deprivation. Eur J Neurosci,1998. 10(11):3451-61.
[86]. W.H. Marshall, Spreading cortical depression of Leao. Physiol Rev,1959. 39(2):239-79.
[87]. R.S. Yoon, P.W. Tsang, F.A. Lenz, et al., Characterization of cortical spreading depression by imaging of intrinsic optical signals. Neuroreport,1996. 7(15-17):2671-4.
[88]. A.M. O'Farrell, D.E. Rex, A. Muthialu, et al., Characterization of optical intrinsic signals and blood volume during cortical spreading depression. Neuroreport,2000. 11(10):2121-5.
[89]. Y. Tomita, M. Tomita, I. Schiszler, et al., Repetitive concentric wave-ring spread of oligemia/hyperemia in the sensorimotor cortex accompanying K(+)-induced spreading depression in rats and cats. Neurosci Lett,2002.322(3):157-60.
[90]. S. Chen, P. Li, W. Luo, et al., Time-varying spreading depression waves in rat cortex revealed by optical intrinsic signal imaging. Neurosci Lett,2006.396(2):132-6.
[91]. M. Guiou, S. Sheth, M. Nemoto, et al., Cortical spreading depression produces long-term disruption of activity-related changes in cerebral blood volume and neurovascular coupling. J Biomed Opt,2005.10(1):11004.
[92]. A.M. Ba, M. Guiou, N. Pouratian, et al., Multiwavelength optical intrinsic signal imaging of cortical spreading depression. J Neurophysiol,2002.88(5):2726-35.
[93]. A.K. Dunn, A. Devor, H. Bolay, et al., Simultaneous imaging of total cerebral hemoglobin concentration, oxygenation, and blood flow during functional activation. Opt Lett,2003.28(1):28-30.
[94]. X. Sun, Y. Wang, S. Chen, et al., Simultaneous monitoring of intracellular pH changes and hemodynamic response during cortical spreading depression by fluorescence-corrected multimodal optical imaging. Neuroimage,2011. 57(3):873-84.
[95]. R. Liu, Q. Huang, B. Li, et al., Extendable, miniaturized multi-modal optical imaging system:cortical hemodynamic observation in freely moving animals. Opt Express,2013.21(2):1911-24.
[96]. F.F. Jobsis, J.H. Keizer, J.C. LaManna, et al., Reflectance spectrophotometry of cytochrome aa3 in vivo. J Appl Physiol,1977.43(5):858-72.
[97]. A.L. Sylvia, M. Rosenthal, Effects of age on brain oxidative metabolism in vivo. Brain Res,1979.165(2):235-48.
[98]. T. Wolf, U. Lindauer, H. Obrig, et al., Systemic nitric oxide synthase inhibition does not affect brain oxygenation during cortical spreading depression in rats:a noninvasive near-infrared spectroscopy and laser-Doppler flowmetry study. J Cereb Blood Flow Metab,1996.16(6):1100-7.
[99]. I. Yuzawa, S. Sakadzic, V.J. Srinivasan, et al., Cortical spreading depression impairs oxygen delivery and metabolism in mice. J Cereb Blood Flow Metab,2011. 32(2):376-86.
[100].J.C. Chang, L.L. Shook, J. Biag, et al., Biphasic direct current shift, haemoglobin desaturation and neurovascular uncoupling in cortical spreading depression Brain, 2010.133(Pt 4):996-1012.
[101].Y.H. Jon, S. Francis, B. Hans, Multispectral color image capture using a liquid crystal tunable filter. Opt. Eng.,2002.41(10):2532-2548.
[102].M. Kohl, U. Lindauer, U. Dirnagl, et al., Separation of changes in light scattering and chromophore concentrations during cortical spreading depression in rats. Opt Lett,1998.23(7):555-7.
[103].M. Kohl, U. Lindauer, G. Royl, et al., Physical model for the spectroscopic analysis of cortical intrinsic optical signals. Phys Med Biol,2000.45(12):3749-64.
[104]. S.A. Prahl, Optical Absorption of Hemoglobin, http://omlc.ogi.edu/spectra/hemoglobin.
[105].G.M. Hale, M.R. Querry, Optical Constants of Water in the 200-nm to 200-microm Wavelength Region. Appl Opt,1973.12(3):555-63.
[106].E. Margoliash, N. Frohwirt, Spectrum of horse-heart cytochrome c. Biochem J, 1959.71(3):570-2.
[107].M. Kuboyama, F.C. Yong, T.E. King, Studies on cytochrome oxidase.8. Preparation and some properties of cardiac cytochrome oxidase. J Biol Chem,1972. 247(20):6375-83.
[108].M. Cope, The development of a near infrared spectroscopy system and its application for noninvasive monitoring of cerebral blood and tissue oxygenation in the newborn infant PHD thesis. Department of Medical Physics and Bioengineering. 1991.
[109].B. Chance, B. Thorell, Fluorescence measurements of mitochondrial pyridine nucleotide in aerobiosis and anaerobiosis. Nature,1959.184:931-4.
[110].E. Dora, A.G. Kovach, Effect of acute arterial hypo-and hypertension on cerebrocortical NAD/NADH redox state and vascular volume. J Cereb Blood Flow Metab,1982.2(2):209-19.
[111]. A. Mayevsky, I. Mizawa, H.A. Sloviter, Surface fluorometry and electrical activity of the isolated rat brain perfused with artificial blood Neurol Res,1981. 3(4):307-16.
[112]. A. Mayevsky, R. Nakache, M. Luger-Hamer, et al., Assessment of transplanted kidney vitality by a multiparametric monitoring system. Transplant Proc,2001. 33(6):2933-4.
[113]. A. Mayevsky, G.G. Rogatsky, Mitochondrial function in vivo evaluated by NADH fluorescence:from animal models to human studies. Am J Physiol Cell Physiol, 2007.292(2):615-40.
[114].K. Shibuki, R. Hishida, H. Murakami, et al., Dynamic imaging of somatosensory cortical activity in the rat visualized by flavoprotein autofluorescence. J Physiol, 2003.549(Pt 3):919-27.
[115].L.G. Whitby, A new method for preparing flavin-adenine dinucleotide. Biochem J, 1953.54(3):437-42.
[116].J.E. Wilson, Studies on the electronic nature of flavin-indole and flavin-purine complexes. Biochemistry,1966.5(4):1351-9.
[117].S.R. Arridge, M. Cope, D.T. Delpy, The theoretical basis for the determination of optical pathlengths in tissue:temporal and frequency analysis. Phys Med Biol,1992. 37(7):1531-60.
[118]. Wang L.H, S.L. Jacques, L.Q. Zheng, MCML-Monte Carlo modeling of photon transport in multi-layered tissues. Computer Methods and Programs in Biomedicine, 1995.47:131-146.
[119].H. Miyake, S. Nioka, A. Zaman, et al., The detection of cytochrome oxidase heme iron and copper absorption in the blood-perfused and blood-free brain in normoxia and hypoxia. Anal Biochem,1991.192(1):149-55.
[120].C.E. Cooper, R. Springett, Measurement of cytochrome oxidase and mitochondrial energetics by near-infrared spectroscopy. Philos Trans R Soc Lond B Biol Sci,1997. 352(1354):669-76.
[121]. J. Mayhew, Y. Zheng, Y. Hou, et al., Spectroscopic analysis of changes in remitted illumination:the response to increased neural activity in brain. Neuroimage,1999. 10(3 Pt 1):304-26.
[122].K. Takano, L.L. Latour, J.E. Formato, et al., The role of spreading depression in focal ischemia evaluated by diffusion mapping. Ann Neurol,1996.39(3):308-18.
[123]. A.F. Cannestra, A.J. Blood, K.L. Black, et al., The evolution of optical signals in human and rodent cortex. Neuroimage,1996.3(3 Pt 1):202-8.
[124].N. Zhou, G.R. Gordon, D. Feighan, et al., Transient swelling, acidification, and mitochondrial depolarization occurs in neurons but not astrocytes during spreading depression. Cereb Cortex,2010.20(11):2614-24.
[125]. S. Chen, Z. Feng, P. Li, et al., In vivo optical reflectance imaging of spreading depression waves in rat brain with and without focal cerebral ischemia J Biomed Opt,2006.11(3):34002.
[126].S. Chen, P. Li, W. Luo, et al., Origin sites of spontaneous cortical spreading depression migrated during focal cerebral ischemia in rats. Neurosci Lett,2006. 403(3):266-70.
[127].M.F. Beal, Mitochondrial dysfunction in neurodegenerative diseases. Biochim Biophys Acta,1998.1366(1-2):211-23.
[128].J.M. Cooper, A.H. Schapira, Mitochondrial dysfunction in neurodegeneration. J Bioenerg Biomembr,1997.29(2):175-83.
[129].M.R. Duchen, Contributions of mitochondria to animal physiology:from homeostatic sensor to calcium signalling and cell death. J Physiol,1999.516 (Pt 1):1-17.
[130].D.G Nicholls, S.L. Budd, Mitochondria and neuronal survival. Physiol Rev,2000. 80(1):315-60.
[131].W.D. Dietrich, Z.C. Feng, H. Leistra, et al., Photothrombotic infarction triggers multiple episodes of cortical spreading depression in distant brain regions. J Cereb Blood Flow Metab,1994.14(1):20-8.
[132].A. Mayevsky, S. Lebourdais, B. Chance, The interrelation between brain PO2 and NADH oxidation-reduction state in the gerbil. J Neurosci Res,1980.5(3):173-82.
[133].M. Hashimoto, Y. Takeda, T. Sato, et al., Dynamic changes of NADH fluorescence images and NADH content during spreading depression in the cerebral cortex of gerbils. Brain Res,2000.872(1-2):294-300.
[134].C. Ayata, H.K. Shin, S. Salomone, et al., Pronounced hypoperfusion during spreading depression in mouse cortex. J Cereb Blood Flow Metab,2004. 24(10):1172-82.
[135].T. Takano, G.F. Tian, W. Peng, et al., Cortical spreading depression causes and coincides with tissue hypoxia Nat Neurosci,2007.10(6):754-62.
[136].S. Chen, P. Li, S. Zeng, et al., Using threshold segmentation methods to measure dynamic vasodilatation in a series of optical images. Proceedings of SPIE,2005. 5696:151-158.
[137]. A.N. Nielsen, M. Fabricius, M. Lauritzen, Scanning laser-Doppler flowmetry of rat cerebral circulation during cortical spreading depression. J Vasc Res,2000. 37(6):513-22.
[138].D.M. Colonna, W. Meng, D.D. Deal, et al., Nitric oxide promotes arteriolar dilation during cortical spreading depression in rabbits. Stroke,1994.25(12):2463-70.
[139]. A.J. Hansen, B. Quistorff, A. Gjedde, Relationship between local changes in cortical blood flow and extracellular K+ during spreading depression. Acta Physiol Scand, 1980.109(1):1-6.
[140]. G. Mies, I. Niebuhr, K.A. Hossmann, Simultaneous measurement of blood flow and glucose metabolism by autoradiographic techniques. Stroke,1981.12(5):581-8.
[141].M. Wahl, M. Lauritzen, L. Schilling, Change of cerebrovascular reactivity after cortical spreading depression in cats and rats. Brain Res,1987.411(1):72-80.
[142].M. Shibata, C.W. Leffler, D.W. Busija, Cerebral hemodynamics during cortical spreading depression in rabbits. Brain Res,1990.530(2):267-74.
[143].S. Chen, M.H. Mohajerani, Y. Xie, et al., Optogenetic analysis of neuronal excitability during global ischemia reveals selective deficits in sensory processing following reperfusion in mouse cortex. J Neurosci,2012.32(39):13510-9.
[144].T.H. Murphy, P. Li, K. Betts, et al., Two-photon imaging of stroke onset in vivo reveals that NMDA-receptor independent ischemic depolarization is the major cause of rapid reversible damage to dendrites and spines. J Neurosci,2008.28(7):1756-72.
[145].U. Dirnagl, R.P. Simon, J.M. Hallenbeck, Ischemic tolerance and endogenous neuroprotection. Trends Neurosci,2003.26(5):248-54.
[146].程海英,利用激光散斑成像技术实时监测微循环血流的动态变化.华中科技大学.2003.
[147].邱建军,激光散斑衬比成像流速测量准确性改善方法研究.华中科技大学.2010.
[148].张红艳,面向临床应用的激光散斑血流成像系统研究.华中科技大学.2012.
[149].L.B. Cohen, B. Hille, R.D. Keynes, et al., Analysis of the potential-dependent changes in optical retardation in the squid giant axon. J Physiol,1971. 218(1):205-37.
[150].I. Tasaki, P.M. Byrne, Optical changes during nerve excitation:interpretation on the basis of rapid structural changes in the superficial gel layer of nerve fibers. Physiol Chem Phys Med NMR,1994.26(1):101-10.
[151].B.A. MacVicar, D. Feighan, A. Brown, et al., Intrinsic optical signals in the rat optic nerve:role for K(+) uptake via NKCC1 and swelling of astrocytes. Glia,2002. 37(2):114-23.
[2]. D.W. Busija, F. Bari, F. Domoki, et al., Mechanisms involved in the cerebrovascular dilator effects of cortical spreading depression. Prog Neurobiol,2008.86(4):379-95.
[3]. A.A.P. Leao, Spreading depression of activity in the cerebral cortex. J Neurophysiol, 1944.7:359-90.
[4]. J.C. Szerb, Glutamate release and spreading depression in the fascia dentata in response to microdialysis with high K+:role of glia Brain Res,1991. 542(2):259-65.
[5]. O. Herreras, GG Somjen, Analysis of potential shifts associated with recurrent spreading depression and prolonged unstable spreading depression induced by microdialysis of elevated K+ in hippocampus of anesthetized rats. Brain Res,1993. 610(2):283-94.
[6]. H. Martins-Ferreira, M. Nedergaard, C. Nicholson, Perspectives on spreading depression. Brain Res Brain Res Rev,2000.32(1):215-34.
[7]. P. Mares, N. Kriz, G. Brozek, et al., Anoxic changes of extracellular potassium concentration in the cerebral cortex of young rats. Exp Neurol,1976.53(1):12-20.
[8]. A.J. Hansen, T. Zeuthen, Extracellular ion concentrations during spreading depression and ischemia in the rat brain cortex. Acta Physiol Scand,1981. 113(4):437-45.
[9]. R.P. Kraig, C. Nicholson, Extracellular ionic variations during spreading depression. Neuroscience,1978.3(11):1045-59.
[10]. GG Somjen, P.G. Aitken, The ionic and metabolic responses associated with neuronal depression of Leao's type in cerebral cortex and in hippocampal formation. An Acad Bras Cienc,1984.56(4):495-504.
[11]. Y. Xie, E. Zacharias, P. Hoff, et al., Ion channel involvement in anoxic depolarization induced by cardiac arrest in rat brain. J Cereb Blood Flow Metab, 1995.15(4):587-94.
[12]. C. Nicholson, Comparative neurophysiology of spreading depression in the cerebellum. An Acad Bras Cienc,1984.56(4):481-94.
[13]. M. Fabricius, L.H. Jensen, M. Lauritzen, Microdialysis of interstitial amino acids during spreading depression and anoxic depolarization in rat neocortex. Brain Res, 1993.612(1-2):61-9.
[14]. A.J. Hansen, C.E. Olsen, Brain extracellular space during spreading depression and ischemia Acta Physiol Scand,1980.108(4):355-65.
[15]. J. Jing, P.G. Aitken, G.G. Somjen, Interstitial volume changes during spreading depression (SD) and SD-like hypoxic depolarization in hippocampal tissue slices. J Neurophysiol,1994.71(6):2548-51.
[16]. R.P. Kraig, C.R. Ferreira-Filho, C. Nicholson, Alkaline and acid transients in cerebellar microenvironment J Neurophysiol,1983.49(3):831-50.
[17]. C.K. Tong, M. Chesler, Endogenous pH shifts facilitate spreading depression by effect on NMD A receptors. J Neurophysiol,1999.81(4):1988-91.
[18]. Z.Q. Xiong, J.L. Stringer, Extracellular pH responses in CA1 and the dentate gyrus during electrical stimulation, seizure discharges, and spreading depression. J Neurophysiol,2000.83(6):3519-24.
[19]. G.G Somjen, Acidification of interstitial fluid in hippocampal formation caused by seizures and by spreading depression. Brain Res,1984.311(1):186-8.
[20]. M. Chesler, R.P. Kraig, Intracellular pH transients of mammalian astrocytes. J Neurosci,1989.9(6):2011-9.
[21]. M. Lauritzen, Cerebral blood flow in migraine and cortical spreading depression. Acta Neurol Scand Suppl,1987.113:1-40.
[22]. C. Yokota, Y. Kuge, Y. Hasegawa, et al., Unique profile of spreading depression in a primate model. J Cereb Blood Flow Metab,2002.22(7):835-42.
[23]. K.C. Brennan, L. Beltran-Parrazal, H.E. Lopez-Valdes, et al., Distinct vascular conduction with cortical spreading depression. J Neurophysiol,2007. 97(6):4143-51.
[24]. A. Charles, K. Brennan, Cortical spreading depression-new insights and persistent questions. Cephalalgia,2009.29(10):1115-24.
[25]. J.M. Smith, D.P. Bradley, M.F. James, et al., Physiological studies of cortical spreading depression. Biol Rev Camb Philos Soc,2006.81(4):457-81.
[26]. A. Gorji, Spreading depression:a review of the clinical relevance. Brain Res Brain Res Rev,2001.38(1-2):33-60.
[27]. M. Peeters, M.J. Gunthorpe, P.J. Strijbos, et al., Effects of pan-and subtype-selective N-methyl-D-aspartate receptor antagonists on cortical spreading depression in the rat:therapeutic potential for migraine. J Pharmacol Exp Ther, 2007.321(2):564-72.
[28]. G.C. Petzold, O. Windmuller, S. Haack, et al., Increased extracellular K+ concentration reduces the efficacy of N-methyl-D-aspartate receptor antagonists to block spreading depression-like depolarizations and spreading ischemia Stroke, 2005.36(6):1270-7.
[29]. M. Lauritzen, A.J. Hansen, The effect of glutamate receptor blockade on anoxic depolarization and cortical spreading depression. J Cereb Blood Flow Metab,1992. 12(2):223-9.
[30]. Leao AAP, M. RS, Propagation of spreading cortical depression. J Neurophysiol, 1945.8:33-45.
[31]. K. Buchheim, F. Weissinger, H. Siegmund, et al., Intrinsic optical imaging reveals regionally different manifestation of spreading depression in hippocampal and entorhinal structures in vitro. Exp Neurol,2002.175(1):76-86.
[32]. I. Vilagi, N. Klapka, H.J. Luhmann, Optical recording of spreading depression in rat neocortical slices. Brain Res,2001.898(2):288-96.
[33]. M. Nedergaard, J. Astrup, Infarct rim:effect of hyperglycemia on direct current potential and [14C]2-deoxyglucose phosphorylation. J Cereb Blood Flow Metab, 1986.6(5):607-15.
[34]. H. Otsuka, K. Ueda, A. Heimann, et al., Effects of cortical spreading depression on cortical blood flow, impedance, DC potential, and infarct size in a rat venous infarct model. Exp Neurol,2000.162(1):201-14.
[35]. L. von Baumgarten, R. Trabold, S. Thal, et al., Role of cortical spreading depressions for secondary brain damage after traumatic brain injury in mice. J Cereb Blood Flow Metab,2008.28(7):1353-60.
[36]. A. Mayevsky, A. Doron, T. Manor, et al., Cortical spreading depression recorded from the human brain using a multiparametric monitoring system. Brain Res,1996. 740(1-2):268-74.
[37]. A.J. Strong, M. Fabricius, M.G. Boutelle, et al., Spreading and synchronous depressions of cortical activity in acutely injured human brain. Stroke,2002. 33(12):2738-43.
[38]. M. Fabricius, S. Fuhr, R. Bhatia, et al., Cortical spreading depression and peri-infarct depolarization in acutely injured human cerebral cortex. Brain,2006. 129(Pt 3):778-90.
[39]. J.P. Dreier, J. Woitzik, M. Fabricius, et al., Delayed ischaemic neurological deficits after subarachnoid haemorrhage are associated with clusters of spreading depolarizations. Brain,2006.129(Pt 12):3224-37.
[40]. C. Dohmen, O.W. Sakowitz, M. Fabricius, et al., Spreading depolarizations occur in human ischemic stroke with high incidence. Ann Neurol,2008.63(6):720-8.
[41]. J.P. Dreier, S. Major, A. Manning, et al., Cortical spreading ischaemia is a novel process involved in ischaemic damage in patients with aneurysmal subarachnoid haemorrhage. Brain,2009.132(Pt 7):1866-81.
[42]. C. Iadecola, From CSD to headache:a long and winding road. Nat Med,2002. 8(2):110-2.
[43]. M. Lauritzen, J.P. Dreier, M. Fabricius, et al., Clinical relevance of cortical spreading depression in neurological disorders:migraine, malignant stroke, subarachnoid and intracranial hemorrhage, and traumatic brain injury. J Cereb Blood Flow Metab,2001.31(1):17-35.
[44]. M.F. James, J.M. Smith, S.J. Boniface, et al., Cortical spreading depression and migraine:new insights from imaging? Trends Neurosci,2001.24(5):266-71.
[45]. M. Lauritzen, Pathophysiology of the migraine aura. The spreading depression theory. Brain,1994.117(Pt 1):199-210.
[46]. M. Lauritzen, Cortical spreading depression in migraine. Cephalalgia,2001. 21(7):757-60.
[47]. K.A. Hossmann, Viability thresholds and the penumbra of focal ischemia. Ann Neurol,1994.36(4):557-65.
[48]. U. Dirnagl, C. Iadecola, M.A. Moskowitz, Pathobiology of ischaemic stroke:an integrated view. Trends Neurosci,1999.22(9):391-7.
[49]. R. Gill, P. Andine, L. Hillered, et al., The effect of MK-801 on cortical spreading depression in the penumbral zone following focal ischaemia in the rat J Cereb Blood Flow Metab,1992.12(3):371-9.
[50]. J.A. Hartings, A.J. Strong, M. Fabricius, et al., Spreading depolarizations and late secondary insults after traumatic brain injury. J Neurotrauma,2009.26(11):1857-66.
[51]. C.S. Roy, C.S. Sherrington, On the Regulation of the Blood-supply of the Brain. J Physiol,1890.11(1-2):85-15817.
[52]. D. Malonek, U. Dirnagl, U. Lindauer, et al., Vascular imprints of neuronal activity: relationships between the dynamics of cortical blood flow, oxygenation, and volume changes following sensory stimulation. Proc Natl Acad Sci U S A,1997. 94(26):14826-31.
[53]. A.K. Dunn, A. Devor, A.M. Dale, et al., Spatial extent of oxygen metabolism and hemodynamic changes during functional activation of the rat somatosensory cortex. Neuroimage,2005.27(2):279-90.
[54]. E.M. Hillman, Optical brain imaging in vivo:techniques and applications from animal to man. J Biomed Opt,2007.12(5):051402.
[55]. M.E. Raichle, Cognitive neuroscience. Bold insights. Nature,2001. 412(6843):128-30.
[56]. A. Zepeda, C. Arias, F. Sengpiel, Optical imaging of intrinsic signals:recent developments in the methodology and its applications. J Neurosci Methods,2004. 136(1):1-1.
[57]. D.K. Hill, R.D. Keynes, Opacity changes in stimulated nerve. J Physiol,1949. 108(3):278-81.
[58]. L.B. Cohen, R.D. Keynes, D. Landowne, Changes in light scattering that accompany the action potential in squid giant axons:potential-dependent components. J Physiol,1972.224(3):701-25.
[59]. R.A. Stepnoski, A. LaPorta, F. Raccuia-Behling, et al., Noninvasive detection of changes in membrane potential in cultured neurons by light scattering Proc Natl Acad Sci U S A,1991.88(21):9382-6.
[60]. B.A. MacVicar, D. Hochman, Imaging of synaptically evoked intrinsic optical signals in hippocampal slices. J Neurosci,1991.11(5):1458-69.
[61]. D. Malonek, A. Grinvald, Interactions between electrical activity and cortical microcirculation revealed by imaging spectroscopy:implications for functional brain mapping. Science,1996.272(5261):551-4.
[62]. A. Grinvald, R.D. Frostig, R.M. Siegel, et al., High-resolution optical imaging of functional brain architecture in the awake monkey. Proc Natl Acad Sci U S A,1991. 88(24):11559-63.
[63]. E. Shtoyerman, A. Arieli, H. Slovin, et al., Long-term optical imaging and spectroscopy reveal mechanisms underlying the intrinsic signal and stability of cortical maps in V1 of behaving monkeys. J Neurosci,2000.20(21):8111-21.
[64]. Y.B. Sirotin, E.M. Hillman, C. Bordier, et al., Spatiotemporal precision and hemodynamic mechanism of optical point spreads in alert primates. Proc Natl Acad Sci U S A,2009.106(43):18390-5.
[65]. B.D. Rubin, L.C. Katz, Optical imaging of odorant representations in the mammalian olfactory bulb. Neuron,1999.23(3):499-511.
[66]. L. Belluscio, L.C. Katz, Symmetry, stereotypy, and topography of odorant representations in mouse olfactory bulbs. J Neurosci,2001.21(6):2113-22.
[67]. M. Wachowiak, L.B. Cohen, Correspondence between odorant-evoked patterns of receptor neuron input and intrinsic optical signals in the mouse olfactory bulb. J Neurophysiol,2003.89(3):1623-39.
[68]. M.W. Spitzer, M.B. Calford, J.C. Clarey, et al., Spontaneous and stimulus-evoked intrinsic optical signals in primary auditory cortex of the cat. J Neurophysiol,2001. 85(3):1283-98.
[69]. N. Harel, N. Mori, S. Sawada, et al., Three distinct auditory areas of cortex (Al, All, and AAF) defined by optical imaging of intrinsic signals. Neuroimage,2000. 11(4):302-12.
[70]. A.J. Blood, N. Pouratian, A.W. Toga, Temporally staggered forelimb stimulation modulates barrel cortex optical intrinsic signal responses to whisker stimulation. J Neurophysiol,2002.88(1):422-37.
[71]. D.B. Polley, C.H. Chen-Bee, R.D. Frostig, Varying the degree of single-whisker stimulation differentially affects phases of intrinsic signals in rat barrel cortex. J Neurophysiol,1999.81(2):692-701.
[72]. M. Jones, J. Berwick, D. Johnston, et al., Concurrent optical imaging spectroscopy and laser-Doppler flowmetry:the relationship between blood flow, oxygenation, and volume in rodent barrel cortex. Neuroimage,2001.13(6 Pt 1):1002-15.
[73]. A. Devor, A.K. Dunn, M.L. Andermann, et al., Coupling of total hemoglobin concentration, oxygenation, and neural activity in rat somatosensory cortex. Neuron, 2003.39(2):353-9.
[74]. P. Gouras, Spreading depression of activity in amphibian retina Am J Physiol,1958. 195(1):28-32.
[75]. H. Martins-Ferreira, GO. de Castro, Light-scattering changes accompanying spreading depression in isolated retina J Neurophysiol,1966.29(4):715-26.
[76]. R.W. Snow, C.P. Taylor, F.E. Dudek, Electrophysiological and optical changes in slices of rat hippocampus during spreading depression. J Neurophysiol,1983. 50(3):561-72.
[77]. P.G. Aitken, GC. Tombaugh, D.A. Turner, et al., Similar propagation of SD and hypoxic SD-like depolarization in rat hippocampus recorded optically and electrically. J Neurophysiol,1998.80(3):1514-21.
[78]. M. Muller, G.G Somjen, Intrinsic optical signals in rat hippocampal slices during hypoxia-induced spreading depression-like depolarization. J Neurophysiol,1999. 82(4):1818-31.
[79]. P.G. Aitken, D. Fayuk, G.G. Somjen, et al., Use of intrinsic optical signals to monitor physiological changes in brain tissue slices. Methods,1999.18(2):91-103.
[80]. S. Bahar, D. Fayuk, G.G. Somjen, et al., Mitochondrial and intrinsic optical signals imaged during hypoxia and spreading depression in rat hippocampal slices. J Neurophysiol,2000.84(1):311-24.
[81]. R. Barer, K.F. Ross, S. Tkaczyk, Refractometry of living cells. Nature,1953. 171(4356):720-4.
[82]. Kreisman NR, LAMANNA JC, LIAO SC, et al., Light transmission as an index of cell volume in hippocampal slices:optical differences of interfaced and submerged positions. Brain Res,1995.693:179-186.
[83]. L. Tao, D. Masri, S. Hrabetova, et al., Light scattering in rat neocortical slices differs during spreading depression and ischemia. Brain Res,2002.952(2):290-300.
[84]. D. Fayuk, P.G. Aitken, G.G. Somjen, et al., Two different mechanisms underlie reversible, intrinsic optical signals in rat hippocampal slices. J Neurophysiol,2002. 87(4):1924-37.
[85]. A.S. Obeidat, R.D. Andrew, Spreading depression determines acute cellular damage in the hippocampal slice during oxygen/glucose deprivation. Eur J Neurosci,1998. 10(11):3451-61.
[86]. W.H. Marshall, Spreading cortical depression of Leao. Physiol Rev,1959. 39(2):239-79.
[87]. R.S. Yoon, P.W. Tsang, F.A. Lenz, et al., Characterization of cortical spreading depression by imaging of intrinsic optical signals. Neuroreport,1996. 7(15-17):2671-4.
[88]. A.M. O'Farrell, D.E. Rex, A. Muthialu, et al., Characterization of optical intrinsic signals and blood volume during cortical spreading depression. Neuroreport,2000. 11(10):2121-5.
[89]. Y. Tomita, M. Tomita, I. Schiszler, et al., Repetitive concentric wave-ring spread of oligemia/hyperemia in the sensorimotor cortex accompanying K(+)-induced spreading depression in rats and cats. Neurosci Lett,2002.322(3):157-60.
[90]. S. Chen, P. Li, W. Luo, et al., Time-varying spreading depression waves in rat cortex revealed by optical intrinsic signal imaging. Neurosci Lett,2006.396(2):132-6.
[91]. M. Guiou, S. Sheth, M. Nemoto, et al., Cortical spreading depression produces long-term disruption of activity-related changes in cerebral blood volume and neurovascular coupling. J Biomed Opt,2005.10(1):11004.
[92]. A.M. Ba, M. Guiou, N. Pouratian, et al., Multiwavelength optical intrinsic signal imaging of cortical spreading depression. J Neurophysiol,2002.88(5):2726-35.
[93]. A.K. Dunn, A. Devor, H. Bolay, et al., Simultaneous imaging of total cerebral hemoglobin concentration, oxygenation, and blood flow during functional activation. Opt Lett,2003.28(1):28-30.
[94]. X. Sun, Y. Wang, S. Chen, et al., Simultaneous monitoring of intracellular pH changes and hemodynamic response during cortical spreading depression by fluorescence-corrected multimodal optical imaging. Neuroimage,2011. 57(3):873-84.
[95]. R. Liu, Q. Huang, B. Li, et al., Extendable, miniaturized multi-modal optical imaging system:cortical hemodynamic observation in freely moving animals. Opt Express,2013.21(2):1911-24.
[96]. F.F. Jobsis, J.H. Keizer, J.C. LaManna, et al., Reflectance spectrophotometry of cytochrome aa3 in vivo. J Appl Physiol,1977.43(5):858-72.
[97]. A.L. Sylvia, M. Rosenthal, Effects of age on brain oxidative metabolism in vivo. Brain Res,1979.165(2):235-48.
[98]. T. Wolf, U. Lindauer, H. Obrig, et al., Systemic nitric oxide synthase inhibition does not affect brain oxygenation during cortical spreading depression in rats:a noninvasive near-infrared spectroscopy and laser-Doppler flowmetry study. J Cereb Blood Flow Metab,1996.16(6):1100-7.
[99]. I. Yuzawa, S. Sakadzic, V.J. Srinivasan, et al., Cortical spreading depression impairs oxygen delivery and metabolism in mice. J Cereb Blood Flow Metab,2011. 32(2):376-86.
[100].J.C. Chang, L.L. Shook, J. Biag, et al., Biphasic direct current shift, haemoglobin desaturation and neurovascular uncoupling in cortical spreading depression Brain, 2010.133(Pt 4):996-1012.
[101].Y.H. Jon, S. Francis, B. Hans, Multispectral color image capture using a liquid crystal tunable filter. Opt. Eng.,2002.41(10):2532-2548.
[102].M. Kohl, U. Lindauer, U. Dirnagl, et al., Separation of changes in light scattering and chromophore concentrations during cortical spreading depression in rats. Opt Lett,1998.23(7):555-7.
[103].M. Kohl, U. Lindauer, G. Royl, et al., Physical model for the spectroscopic analysis of cortical intrinsic optical signals. Phys Med Biol,2000.45(12):3749-64.
[104]. S.A. Prahl, Optical Absorption of Hemoglobin, http://omlc.ogi.edu/spectra/hemoglobin.
[105].G.M. Hale, M.R. Querry, Optical Constants of Water in the 200-nm to 200-microm Wavelength Region. Appl Opt,1973.12(3):555-63.
[106].E. Margoliash, N. Frohwirt, Spectrum of horse-heart cytochrome c. Biochem J, 1959.71(3):570-2.
[107].M. Kuboyama, F.C. Yong, T.E. King, Studies on cytochrome oxidase.8. Preparation and some properties of cardiac cytochrome oxidase. J Biol Chem,1972. 247(20):6375-83.
[108].M. Cope, The development of a near infrared spectroscopy system and its application for noninvasive monitoring of cerebral blood and tissue oxygenation in the newborn infant PHD thesis. Department of Medical Physics and Bioengineering. 1991.
[109].B. Chance, B. Thorell, Fluorescence measurements of mitochondrial pyridine nucleotide in aerobiosis and anaerobiosis. Nature,1959.184:931-4.
[110].E. Dora, A.G. Kovach, Effect of acute arterial hypo-and hypertension on cerebrocortical NAD/NADH redox state and vascular volume. J Cereb Blood Flow Metab,1982.2(2):209-19.
[111]. A. Mayevsky, I. Mizawa, H.A. Sloviter, Surface fluorometry and electrical activity of the isolated rat brain perfused with artificial blood Neurol Res,1981. 3(4):307-16.
[112]. A. Mayevsky, R. Nakache, M. Luger-Hamer, et al., Assessment of transplanted kidney vitality by a multiparametric monitoring system. Transplant Proc,2001. 33(6):2933-4.
[113]. A. Mayevsky, G.G. Rogatsky, Mitochondrial function in vivo evaluated by NADH fluorescence:from animal models to human studies. Am J Physiol Cell Physiol, 2007.292(2):615-40.
[114].K. Shibuki, R. Hishida, H. Murakami, et al., Dynamic imaging of somatosensory cortical activity in the rat visualized by flavoprotein autofluorescence. J Physiol, 2003.549(Pt 3):919-27.
[115].L.G. Whitby, A new method for preparing flavin-adenine dinucleotide. Biochem J, 1953.54(3):437-42.
[116].J.E. Wilson, Studies on the electronic nature of flavin-indole and flavin-purine complexes. Biochemistry,1966.5(4):1351-9.
[117].S.R. Arridge, M. Cope, D.T. Delpy, The theoretical basis for the determination of optical pathlengths in tissue:temporal and frequency analysis. Phys Med Biol,1992. 37(7):1531-60.
[118]. Wang L.H, S.L. Jacques, L.Q. Zheng, MCML-Monte Carlo modeling of photon transport in multi-layered tissues. Computer Methods and Programs in Biomedicine, 1995.47:131-146.
[119].H. Miyake, S. Nioka, A. Zaman, et al., The detection of cytochrome oxidase heme iron and copper absorption in the blood-perfused and blood-free brain in normoxia and hypoxia. Anal Biochem,1991.192(1):149-55.
[120].C.E. Cooper, R. Springett, Measurement of cytochrome oxidase and mitochondrial energetics by near-infrared spectroscopy. Philos Trans R Soc Lond B Biol Sci,1997. 352(1354):669-76.
[121]. J. Mayhew, Y. Zheng, Y. Hou, et al., Spectroscopic analysis of changes in remitted illumination:the response to increased neural activity in brain. Neuroimage,1999. 10(3 Pt 1):304-26.
[122].K. Takano, L.L. Latour, J.E. Formato, et al., The role of spreading depression in focal ischemia evaluated by diffusion mapping. Ann Neurol,1996.39(3):308-18.
[123]. A.F. Cannestra, A.J. Blood, K.L. Black, et al., The evolution of optical signals in human and rodent cortex. Neuroimage,1996.3(3 Pt 1):202-8.
[124].N. Zhou, G.R. Gordon, D. Feighan, et al., Transient swelling, acidification, and mitochondrial depolarization occurs in neurons but not astrocytes during spreading depression. Cereb Cortex,2010.20(11):2614-24.
[125]. S. Chen, Z. Feng, P. Li, et al., In vivo optical reflectance imaging of spreading depression waves in rat brain with and without focal cerebral ischemia J Biomed Opt,2006.11(3):34002.
[126].S. Chen, P. Li, W. Luo, et al., Origin sites of spontaneous cortical spreading depression migrated during focal cerebral ischemia in rats. Neurosci Lett,2006. 403(3):266-70.
[127].M.F. Beal, Mitochondrial dysfunction in neurodegenerative diseases. Biochim Biophys Acta,1998.1366(1-2):211-23.
[128].J.M. Cooper, A.H. Schapira, Mitochondrial dysfunction in neurodegeneration. J Bioenerg Biomembr,1997.29(2):175-83.
[129].M.R. Duchen, Contributions of mitochondria to animal physiology:from homeostatic sensor to calcium signalling and cell death. J Physiol,1999.516 (Pt 1):1-17.
[130].D.G Nicholls, S.L. Budd, Mitochondria and neuronal survival. Physiol Rev,2000. 80(1):315-60.
[131].W.D. Dietrich, Z.C. Feng, H. Leistra, et al., Photothrombotic infarction triggers multiple episodes of cortical spreading depression in distant brain regions. J Cereb Blood Flow Metab,1994.14(1):20-8.
[132].A. Mayevsky, S. Lebourdais, B. Chance, The interrelation between brain PO2 and NADH oxidation-reduction state in the gerbil. J Neurosci Res,1980.5(3):173-82.
[133].M. Hashimoto, Y. Takeda, T. Sato, et al., Dynamic changes of NADH fluorescence images and NADH content during spreading depression in the cerebral cortex of gerbils. Brain Res,2000.872(1-2):294-300.
[134].C. Ayata, H.K. Shin, S. Salomone, et al., Pronounced hypoperfusion during spreading depression in mouse cortex. J Cereb Blood Flow Metab,2004. 24(10):1172-82.
[135].T. Takano, G.F. Tian, W. Peng, et al., Cortical spreading depression causes and coincides with tissue hypoxia Nat Neurosci,2007.10(6):754-62.
[136].S. Chen, P. Li, S. Zeng, et al., Using threshold segmentation methods to measure dynamic vasodilatation in a series of optical images. Proceedings of SPIE,2005. 5696:151-158.
[137]. A.N. Nielsen, M. Fabricius, M. Lauritzen, Scanning laser-Doppler flowmetry of rat cerebral circulation during cortical spreading depression. J Vasc Res,2000. 37(6):513-22.
[138].D.M. Colonna, W. Meng, D.D. Deal, et al., Nitric oxide promotes arteriolar dilation during cortical spreading depression in rabbits. Stroke,1994.25(12):2463-70.
[139]. A.J. Hansen, B. Quistorff, A. Gjedde, Relationship between local changes in cortical blood flow and extracellular K+ during spreading depression. Acta Physiol Scand, 1980.109(1):1-6.
[140]. G. Mies, I. Niebuhr, K.A. Hossmann, Simultaneous measurement of blood flow and glucose metabolism by autoradiographic techniques. Stroke,1981.12(5):581-8.
[141].M. Wahl, M. Lauritzen, L. Schilling, Change of cerebrovascular reactivity after cortical spreading depression in cats and rats. Brain Res,1987.411(1):72-80.
[142].M. Shibata, C.W. Leffler, D.W. Busija, Cerebral hemodynamics during cortical spreading depression in rabbits. Brain Res,1990.530(2):267-74.
[143].S. Chen, M.H. Mohajerani, Y. Xie, et al., Optogenetic analysis of neuronal excitability during global ischemia reveals selective deficits in sensory processing following reperfusion in mouse cortex. J Neurosci,2012.32(39):13510-9.
[144].T.H. Murphy, P. Li, K. Betts, et al., Two-photon imaging of stroke onset in vivo reveals that NMDA-receptor independent ischemic depolarization is the major cause of rapid reversible damage to dendrites and spines. J Neurosci,2008.28(7):1756-72.
[145].U. Dirnagl, R.P. Simon, J.M. Hallenbeck, Ischemic tolerance and endogenous neuroprotection. Trends Neurosci,2003.26(5):248-54.
[146].程海英,利用激光散斑成像技术实时监测微循环血流的动态变化.华中科技大学.2003.
[147].邱建军,激光散斑衬比成像流速测量准确性改善方法研究.华中科技大学.2010.
[148].张红艳,面向临床应用的激光散斑血流成像系统研究.华中科技大学.2012.
[149].L.B. Cohen, B. Hille, R.D. Keynes, et al., Analysis of the potential-dependent changes in optical retardation in the squid giant axon. J Physiol,1971. 218(1):205-37.
[150].I. Tasaki, P.M. Byrne, Optical changes during nerve excitation:interpretation on the basis of rapid structural changes in the superficial gel layer of nerve fibers. Physiol Chem Phys Med NMR,1994.26(1):101-10.
[151].B.A. MacVicar, D. Feighan, A. Brown, et al., Intrinsic optical signals in the rat optic nerve:role for K(+) uptake via NKCC1 and swelling of astrocytes. Glia,2002. 37(2):114-23.