Transcranial near infrared laser treatment (NILT) increases cortical adenosine-5′-triphosphate (ATP) content following embolic strokes in rabbits
Transcranial near infrared laser treatment (NILT) increases cortical adenosine-5′-triphosphate (ATP) content following embolic strokes in rabbits
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DOI：
10.1016/j.brainres.2009.10.022
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发表时间：
2010-01-08
期刊：
影响因子：
2.9
通讯作者：
De Taboada, Luis
中科院分区：
文献类型：
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作者：
Lapchak, Paul A.;De Taboada, Luis
经颅近红外激光治疗（NILT）可改善栓塞兔栓塞性卒中后的行为结局和急性缺血性卒中（AIS）患者的临床评分;然而，NILT神经保护作用涉及的细胞机制尚未阐明。有人提出，线粒体能量产生可能是NILT反应的基础，但这尚未通过体内栓塞性卒中模型得到证实。因此，我们使用兔小凝块栓塞性卒中模型（RSCEM）评价了NILT对皮质ATP含量的影响，该模型最初用于证明NILT疗效并启动NEST-1临床试验。栓塞后5分钟，将家兔暴露于使用808 nm激光源的NILT 2分钟，该激光源被驱动以输出连续波（CW）或脉冲波模式（PW）。栓塞后3小时，切除大脑皮层并进行处理，以使用标准的胰蛋白酶-荧光素酶测定法测量ATP含量。将NILT处理的兔与假处理的栓塞兔和幼稚对照兔直接比较。与未处理兔相比，栓塞使缺血皮质中的皮质ATP含量降低了45%，CW NILT减弱了这种降低，导致皮质ATP含量与假栓塞组相比增加了41%（p> 0.05）。ATP含量的绝对增加是22.5%相比，幼稚兔。在PW NILT（输送的能量是CW的5倍（PW1）和35倍（PW2））后，我们测量到与假栓塞组相比，皮质ATP含量分别增加了157%（PW1 p = 0.0032）和221%（PW2 p = 0.0001）。这表示与幼稚对照兔相比，ATP含量增加了41%和77%。这是第一次证明栓塞可以降低兔皮质中的ATP含量，NILT显著增加栓塞兔皮质中的ATP含量，这一效应与皮质通量和NILT递送模式相关。这些数据为NILT后临床改善相关的分子机制提供了新的见解。(C)2009爱思唯尔有限公司版权所有。
Transcranial near infrared laser therapy (NILT) improves behavioral outcome following embolic strokes in embolized rabbits and clinical rating scores in acute ischemic stroke (AIS) patients; however, the cellular mechanism(s) involved in NILT neuroprotection have not been elucidated. It has been proposed that mitochondrial energy production may underlie a response to NILT, but this has not been demonstrated using an in vivo embolic stroke model. Thus, we evaluated the effect of NILT on cortical ATP content using the rabbit small clot embolic stroke model (RSCEM), the model originally used to demonstrate NILT efficacy and initiate the NEST-1 clinical trial. Five minutes following embolization, rabbits were exposed to 2 min of NILT using an 808 nm laser source, which was driven to output either continuous wave (CW), or pulsed wave modes (PW). Three hours after embolization, the cerebral cortex was excised and processed for the measurement of ATP content using a standard luciferin-luciferase assay. NILT-treated rabbits were directly compared to sham-treated embolized rabbits and naive control rabbits. Embolization decreased cortical ATP content in ischemic cortex by 45% compared to naive rabbits, a decrease that was attenuated by CW NILT which resulted in a 41% increase in cortical ATP content compared to the sham embolized group (p>0.05). The absolute increase in ATP content was 22.5% compared to naive rabbits. Following PW NILT, which delivered 5 (PW1) and 35 (PW2) times more energy than CW, we measured a 157% (PW1 p=0.0032) and 221% (PW2 p=0.0001) increase in cortical ATP content, respectively, compared to the sham embolized group. That represented a 41% and 77% increase in ATP content compared to naive control rabbits. This is the first demonstration that embolization can decrease ATP content in rabbit cortex and that NILT significantly increases cortical ATP content in embolized rabbits, an effect that is correlated with cortical fluence and the mode of NILT delivery. The data provide new insight into the molecular mechanisms associated with clinical improvement following NILT. (C) 2009 Elsevier B.V. All rights reserved.