Mitochondrial Cytochrome C Oxidase Expression in the Central Nervous System Is Elevated at Sites of Pressure Gradient Elevation but Not Absolute Pressure Increase
Mitochondrial Cytochrome C Oxidase Expression in the Central Nervous System Is Elevated at Sites of Pressure Gradient Elevation but Not Absolute Pressure Increase
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DOI：
10.1002/jnr.22120
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发表时间：
2009-10-01
影响因子：
4.2
通讯作者：
Yu, Dao-Yi
中科院分区：
文献类型：
--
作者：
Balaratnasingam, Chandrakumar;Pham, Duy;Yu, Dao-Yi
由于缺乏合适的实验模型，很难分离线粒体在与绝对压力升高和压力梯度增加相关的中枢神经系统疾病中的致病作用。创伤性脑损伤（TBI）和脑积水的实验模型用于检查中枢神经系统压力升高后的线粒体反应；然而，在这些先前的研究中存在多种作用于大脑的致病因素，因此难以确定诱导的变化是机械损伤、颅内压升高还是其他致病因素的结果。通过直接监测和控制眼内、颅内和血管腔室的压力，我们使用猪视神经（典型的中央白质束）来比较绝对压力升高和压力梯度增加区域之间细胞色素c氧化酶（CcO）水平的时间序列。我们证明，在没有外伤性损伤的情况下，压力梯度升高会上调整个梯度部位的CcO水平，其方式类似于先前报道的脑积水。我们还证明，CcO变化不会在绝对压力上升后发生。这些发现与我们最近的报告一起表明，线粒体在压力梯度增加后对轴突损伤启动早期代偿反应。我们的结果外推还表明，TBI中CcO水平的下降可能是继发于机械损伤的。这项研究强调了压力梯度在调节中枢神经系统线粒体功能中的重要性。(C) 2009 Wiley-Liss, Inc。
The paucity of suitable experimental models has made it difficult to isolate the pathogenic role of mitochondria in central nervous system diseases associated with absolute pressure elevation and increased pressure gradients. Experimental models of traumatic brain injury (TBI) and hydrocephalus have been useful for examining the mitochondrial response following pressure increase in the central nervous system; however, the presence of multiple pathogenic factors acting on the brain in these previous studies has made it difficult to determine whether the induced changes were a result of mechanical damage, intracranial pressure elevation, or other pathogenic factors. By direct monitoring and control of pressures in the intraocular, intracranial, and vascular compartments, we use the pig optic nerve, a typical central white matter tract, to compare the temporal sequence of cytochrome c oxidase (CcO) levels between regions of absolute pressure elevation and pressure gradient increase. We demonstrate that a rise in pressure gradient without traumatic injury up-regulates CcO levels across the site of the gradient, in a manner similar to what has been previously reported for hydrocephalus. We also demonstrate that CcO changes do not occur following an absolute pressure rise. These findings taken together with our recent reports suggest that mitochondria initiate an early compensatory response to axonal damage following pressure gradient increase. Extrapolation of our results also suggests that decreased CcO levels in TBI may be secondary to mechanical damage. This study emphasises the importance of pressure gradients in regulating mitochondrial function in the central nervous system. (C) 2009 Wiley-Liss, Inc.