Why Is the Nervous System Vulnerable to Oxidative Stress?
Why Is the Nervous System Vulnerable to Oxidative Stress?
复制标题
DOI：
10.1007/978-1-60327-514-9_2
复制
发表时间：
2011-01-01
期刊：
影响因子：
--
通讯作者：
Friedman, Joseph
中科院分区：
文献类型：
--
作者：
Friedman, Joseph
由于以下原因，神经系统特别容易受到活性氧（ROS）介导的损伤。(1)大脑对高能量需求的高耗氧量，即高O-2消耗，导致产生过量的ROS。(2)神经元膜富含多不饱和脂肪酸（PUPA），特别容易受到自由基的攻击。(3)细胞膜表面积与细胞质体积之比很高。(4)专门的神经元传导和突触传递活动依赖于有效的膜功能。(5)延长的轴突形态易于发生外周损伤。(6)神经元解剖网络容易受到破坏。(7)兴奋毒性谷氨酸是引起氧化应激（OS）的主要效应物。(8)神经元膜上的高Ca ~（2+）运输和离子运输的干扰增加了细胞内Ca ~（2+），通常导致OS。（9）神经递质的自动氧化可以产生O-2和醌，还原谷胱甘肽。(10)铁在整个大脑中形成，并且脑损伤容易释放能够催化自由基反应的铁离子。(11)抗氧化防御机制是适度的，特别是低水平的过氧化氢酶，谷胱甘肽过氧化物酶和维生素E。(12)ROS直接下调紧密连接蛋白，并间接激活基质金属蛋白酶（AMP），有助于打开血脑屏障（BBB）。(13)活化的小胶质细胞在一个永久的过程中产生ROS和细胞因子。(14)细胞色素P450产生ROS。(15)营养支持的丧失可以激活NADPH氧化酶，这增加了ROS。(16)继发于自发性、医源性或创伤性原因的神经组织内血红蛋白的存在是神经毒性的。血红素和铁被释放并促进ROS。(17)神经元线粒体产生O-2。(18)NO与超氧化物的相互作用也可能与神经元变性有关。(19)神经元细胞是非复制的，因此对ROS敏感。与其他器官相比，神经元网络可能特别容易受到ROS介导的损伤，因为大脑的以下解剖学，生理学和生化特性。
The nervous system is especially vulnerable to reactive oxygen species (ROS)-mediated injury for the following reasons. (1) High oxygen consumption of the brain for high energy needs, that is, high O-2 consumption, results in excessive ROS produced. (2) Neuronal membranes are rich in polyunsaturated fatty acids (PUPA), which are particularly vulnerable to free radical attack. (3) The ratio of membrane surface area to cytoplasmic volume is high. (4) Specialized neuronal conduction and synaptic transmission activity depend on efficient membrane function. (5) Extended axonal morphology is prone to peripheral injury. (6) Neuronal anatomic network is vulnerable to disruptions. (7) The excitotoxic glutamate is the major effector that causes oxidative stress (OS). (8) The high Ca2+ traffic across neuronal membranes and interference of ion transport increase intracellular Ca2+, often leading to OS. (9) Auto-oxidation of neurotransmitters can generate O-2 and quinones that reduce glutathione. (10) Iron is formed throughout the brain, and brain damage readily releases iron ions capable of catalyzing free radical reactions. (11) Antioxidant defense mechanisms are modest, in particular, low levels of catalase, glutathione peroxidase, and vitamin E. (12) ROS directly downregulate proteins of tight junctions and indirectly activate matrix metalloproteinases (AMP) that contribute to open the blood brain barrier (BBB). (13) Activated microglia produce ROS and cytokines in a perpetual process. (14) Cytochrome P450 produces ROS. (15) Loss of trophic support can activate NADPH oxidase, which increases ROS. (16) The presence of hemoglobin within the neural tissues secondary to spontaneous, iatrogenic, or traumatic causes is neurotoxic. Heme and iron are released and promote ROS. (17) Neuronal mitochondria generate O-2. (18) The interaction of NO with superoxide can be implicated also in neuronal degeneration. (19) Neuronal cells are nonreplicating and thus are sensitive to ROS. In comparison with other organs, the neuronal network may be especially vulnerable to ROS-mediated injury because of the following anatomic, physiological, and biochemical properties of the brain.