Conti Alfredo, Miscusi Massimo, Cardali Salvatore, Germanò Antonino, Suzuki Hisanori, Cuzzocrea Salvatore, Tomasello Francesco
Department of Neuroscience, University of Messina, Policlinico Universitario, Messina, Italy.
Brain Res Rev. 2007 Apr;54(1):205-18. doi: 10.1016/j.brainresrev.2007.01.013.
Nitric oxide (NO) is a unique informational molecule involved in a variety of physiological processes in the central nervous system (SNS). It has been demonstrated that it can exert both protective and detrimental effects in several diseases states of the CNS, including spinal cord injury (SCI). The effects of NO on the spinal cord depend on several factors such as: concentration of produced NO, activity of different synthase isoforms, cellular source of production and time of release. Basically, it has been shown that low NO concentrations may play a role in physiologic processes, whereas large amounts of NO may be detrimental by increasing oxidative stress. However, this does not explain all the discrepancies evidenced studying the effects of NO in SCI models. The analysis of the different synthase isoforms, of their temporal profile of activation and cellular source has shed light on this topic. Two post-injury time intervals can be defined with reference to the NO production: immediately after injury and several hours-to-days later. The initial immediate peak of NO production after injury is due to the up-regulation of the neuronal NO synthase (nNOS) in resident spinal cord cells. The late peak is due primarily to the activity of inducible NOS (nNOS) produced by inflammatory infiltrating cells. High NO levels produced by up-regulated nNOS and iNOS are neurotoxic; the down-regulation of nNOS corresponds temporally to the expression of iNOS. On the bases of the evidence, therapeutic approaches should be aimed: (1) to reduce the NO-elicited damage by inhibition of specific synthases according to the temporal profile of activation; (2) by maintaining physiologic amount of NO to keep the induction of iNOS.
一氧化氮（NO）是一种独特的信息分子，参与中枢神经系统（SNS）的多种生理过程。已经证明，它在中枢神经系统的几种疾病状态中，包括脊髓损伤（SCI），既能发挥保护作用，也能产生有害影响。NO对脊髓的影响取决于几个因素，如：产生的NO浓度、不同合酶同工型的活性、产生的细胞来源和释放时间。基本上，已经表明低浓度的NO可能在生理过程中起作用，而大量的NO可能通过增加氧化应激而有害。然而，这并不能解释在研究SCI模型中NO的作用时所发现的所有差异。对不同合酶同工型、它们的激活时间谱和细胞来源的分析为这个问题提供了线索。根据NO的产生可以定义两个损伤后的时间间隔：损伤后立即和数小时至数天后。损伤后NO产生的最初即时峰值是由于脊髓常驻细胞中神经元型一氧化氮合酶（nNOS）的上调。后期峰值主要是由于炎症浸润细胞产生的诱导型一氧化氮合酶（iNOS）的活性。上调的nNOS和iNOS产生的高NO水平具有神经毒性；nNOS的下调在时间上与iNOS的表达相对应。基于这些证据，治疗方法应旨在：（1）根据激活的时间谱通过抑制特定合酶来减少NO引起的损伤；（2）通过维持生理量的NO来抑制iNOS的诱导。
